The addition of daratumumab to lenalidomide and dexamethasone resulted in superior response rate and progression-free survival, as compared with lenalidomide and dexamethasone alone, at a cost of ...more frequent neutropenia and infusion reactions.
The incorporation of proteasome inhibitors and immunomodulatory drugs into the standard of care has improved outcomes in patients with multiple myeloma over the past 10 years,
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but most patients still eventually have a relapse.
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Relapse can occur even after standard complete remission in the context of first-line therapy, and studies are therefore evaluating deeper responses in a category termed “minimal residual disease–negative” (i.e., results below the threshold for minimal residual disease) that is prognostic with regard to a rate of disease progression in a time-to-event analysis and overall survival.
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However, this category of minimal residual disease status has . . .
KW-2478 is a novel non-ansamycin Hsp90 inhibitor with modest single-agent activity in relapsed/refractory myeloma but which shows synergistic antimyeloma activity with bortezomib (BTZ) in preclinical ...studies. This study determined the safety, preliminary clinical activity, and pharmacokinetics of KW-2478, an Hsp90 inhibitor, in combination with BTZ in patients with relapsed/refractory multiple myeloma (MM).
Phase I dose escalation determined the recommended phase II dose (RP2D) of KW-2478 plus BTZ, which was then used during phase II.
The maximum tolerated dose was not reached during phase I and the RP2D was KW-2478 175 mg m
plus BTZ 1.3 mg m
on days 1, 4, 8, and 11 every 3 weeks. In the efficacy evaluable phase I/II population treated at the RP2D (n=79), the objective response rate was 39.2% (95% confidence interval: 28.4-50.9%), clinical benefit rate 51.9% (40.4-63.3%), median progression-free survival 6.7 (5.9-not reached (NR)) months, and median duration of response 5.5 (4.9-NR) months. In the phase I/II safety population (n=95), the most frequently observed treatment-related grade 3/4 adverse events were diarrhoea, fatigue, and neutropenia (each in 7.4% of patients), and nausea and thrombocytopenia (each in 5.3%).
KW-2478 plus BTZ was well tolerated with no apparent overlapping toxicity in patients with relapsed/refractory MM. The antimyeloma activity of KW-2478 in combination with BTZ as scheduled in this trial appeared relatively modest; however, the good tolerability of the combination would support further exploration of alternate dosing schedules and combinations.
In this work, an advanced machine learning technique named diffusion maps is applied for array-based earthquake-explosion discrimination. We rely on prior work that utilizes the diffusion map-based ...discrimination approach for data collected from a single seismometer. The discrimination task is an essential component of the Comprehensive Nuclear-Test-Ban Treaty verification regime and since many of the International Monitoring System (IMS) stations consist of arrays, the extension to array based processing is of interest. The proposed method includes a pre-processing step, which constructs time–frequency representations of the P-wave and S-wave seismograms followed by a non-linear dimensionality reduction step. Discrimination is performed in the low-dimensional space. The performance of the presented algorithm is demonstrated on a data set from Southern Israel, recorded at the IMS seismic array of Mt. Meron (MMAI). We show that the diffusion maps-based approach enables to enhance the discrimination capabilities of seismic arrays, even when processing low-magnitude events.
Modeling and analysis of students’ performance is a common task that is aimed at identifying important factors that affect the learning process. Typically, the analysis uses one-dimensional input ...parameters. However, with the advancement of data collections tools, many of the gathered educational datasets have become high-dimensional. Hence, the use of standard statistical methods may be limited in cases that the initial data unit is a vector.
This paper proposes to use vector input units, which consist of student performance trajectories, for identifying statistical differences in college performances for several populations of college students. Two kernel based methods named diffusion maps and the kernel two-sample test are utilized. Diffusion maps generates a low-dimensional representation of the data, in which important characteristic factors are identified. The kernel two-sample test is a statistical test for comparing whether high-dimensional samples are drawn from two different probability distributions. The two methods are combined into a unified framework.
Two case studies, which are processed similarly, are presented. The first tests for significant distributional differences between students with or without learning disabilities. Our results show that these groups’ performances is significantly different. The second case-study analyzes whether the SAT score impacts students’ performance throughout their 4-year of studies. It was found that significant distribution differences in performance are only present for groups of students having a very high or a very low SAT score. Thus, the SAT score is only weakly correlated to students’ college performance.
•Kernel methods are used to model and analyze student performance trajectories.•Diffusion maps provided visualization and identification of performance groups.•Average grade and the performance’s trend differentiate between the groups.•The kernel two-sample test was applied for statistical testing.•It was found that learning disabilities and SAT scores affect college performance.
Discrimination between earthquakes and explosions is an essential component of nuclear test monitoring. However, the discrimination methods currently employed by the Comprehensive Nuclear-Test-Ban ...Treaty Organization (CTBTO) are sometimes less effective for regional events. For instance, five seismic events whose epicenters lie near the Sea of Galilee were reported by the CTBTO in July of 2018. Those were relatively strong regional events, observed by primary stations hundreds of kilometers from the epicenter. Notably, three out of those five events were not screened out by the CTBTO as natural events. In this work, a diffusion maps-based discrimination method is configured and applied for the July 2018 Sea of Galilee seismic events. New features are introduced to the method, in order to enhance automation and computational efficiency and facilitate its use in operational settings. In the first of which, waveform segments are selected by relying on calculated arrivals rather than observed arrivals, alleviating the need for detection by a human analyst. In a further extension of the method, the low-dimensional diffusion maps representation from the training set is extended to a test set by means of geometric harmonics, relieving the need for the re-calculation of the diffusion maps coordinates for the entire data set as each new event comes in. Utilizing a network of three stations, we show that this machine learning method classifies as earthquakes all the July 2018 Sea of Galilee seismic events with durational magnitude Md > 2.3. In the context of the CTBT, the method can be used as part of an Expert Technical Analysis in order to aid the State Party concerned to identify the source of specific events.
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•Machine learning methods expose connections between strategies and performances.•Kernel multiplication yields graph/map of the business performance datasets.•Typical profiles are ...extracted from the map and reveal successful strategic choices.•The approach overcomes limitations of linear methods that generate coarser models.
The aim of this paper is to investigate the impact of strategic planning on service small and medium size enterprises’ (SMEs) performance. A machine learning methodology, based on an alternating diffusion process, is applied for organizing the SMEs into a network/graph, and generating management profiles. The method relies on ideas from non-linear dimensionality reduction, where a data-set is parameterized by a small number of intrinsic parameters. Recent advances in this field allow for the construction of a common intrinsic representation for two related dataset by using kernel multiplication. In this work, the method is applied to two related datasets that describe a business from two angles: strategic planning and performance. The goal is to reveal underlying hidden strategic patterns that influence SMEs’ performance.
The proposed methods are applied to a dataset containing planning and performance measures of 467 businesses. The obtained model yields an SME graph, where SMEs that share similar planning strategies and performances are located close to each other. Thus, the model generates typical strategic planning and performance profiles, describing distinct groups of SMEs. The study reveals two different planning strategies emphasizing different management approaches that lead to successful performance. Thus, in service SMEs there is more than one way to enhance performance via management strategy. Differentiating between various planning strategies was enabled by utilizing kernel based machine learning methods, thereby overcoming limitations of linear methods that cannot provide such sensitive profile configurations.
Summary
Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) ...in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy‐based induction fell significantly, being largely replaced by bortezomib‐based regimens. The two‐year complete response rate increased from 22% to 42%. The five‐year progression‐free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.
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