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SUMMARY: BACKGROUND: Bortezomib, lenalidomide, and dexamethasone (VRd) is a standard therapy for newly diagnosed multiple myeloma (NDMM). Carfilzomib, a next-generation proteasome inhibitor, in combination with lenalidomide, and dexamethasone (KRd) has shown excellent efficacy in phase II trials and may improve outcomes compared with VRd. METHODS: In this randomized, open label, phase 3 trial, we recruited patients with NDMM, aged 18 years and older, who were not planned for immediate autologous stem-cell transplant (ASCT). Key inclusion was absence of the following high-risk features (del17p, t(14;16), t(14;20), plasma cell leukemia) and Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients were randomized (1:1) to receive VRd or KRd for 36 weeks followed by a 2(nd) randomization (1:1) to indefinite versus 2 years of lenalidomide maintenance. Allocation was stratified by intent to ASCT at disease progression and was not masked to investigators and patients. VRd regimen included bortezomib 1·3 mg/m(2) on days 1, 4, 8, and 11 (d 1, 8 for cycles 9–12), lenalidomide 25 mg daily on days 1–14, and dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, 12 for twelve 3-week cycles. KRd regimen included carfilzomib 36 mg/m(2) on days 1, 2, 8, 9, 15, 16, lenalidomide 25 mg daily on days 1–21 and dexamethasone 40 mg on days 1, 8, 15, and 22 for nine 4-week cycles. The primary endpoint was progression-free survival, defined as the time from first randomization to disease progression or death, analyzed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete, all patients have completed induction therapy, and patients continue on maintenance as per second randomization and follow up is ongoing. The trial is registered at ClinicalTrials.gov:NCT01863550. FINDINGS: Between December 6, 2013 and February 6, 2019, we randomly assigned 1087 patients at 272 participating institutions (542 to VRd, 545 to KRd). At an estimated median (IQR) follow-up of 9 (5–23) months from randomization, median PFS was 34·4 (95% CI 30·1-NE) months for VRd compared with 34·6 (95% CI 28·8–37·8) months for KRd; the PFS treatment hazard ratio (HR=KRd/VRd) was 1·04 (95% CI 0·83–1·31); P=0·74. The most common grade 3–4 non-hematologic adverse events included fatigue (34 [6%] vs. 29 [6%]), hyperglycemia (23 [4%] vs. 34[7%]), peripheral neuropathy (44 [8%]vs. 4 [

We report on a Game based learning system, in which players can freely explore consequential judgment and dynamic decision making tasks based on an inquiry learning paradigm. The simplified dynamic game model integrates and balances several game components allowing players reading and steering minds of in-game characters, and subsequently influencing game stories. We implemented parts of a leadership competency framework allowing players discovering and influencing key stakeholders in order to influence key outcomes.

The impact of converging technologies on legal practice and criminology is being investigated in a forward looking study intended for practitioners and policy makers in the field of legislation, crime prevention, and law enforcement. This report consists of three parts. The first part describes the state of the art and future expectations on nano-, bio-, ICT and cognitive science and technology, as well as their convergence. The second part describes the (future) applicability of converging technologies to our application domain, in particular in three cases. This part ends with scenarios that are used as a means to ‘visualize’ the developments and an input for the impact analysis. In the third part the scenarios are analysed on their ethical, legal and social implications. This part describes the major social and normative trends that are observed.

Although in many organisations projects are run according to a standard procedure many projects run out of time and budget, don't achieve the required quality standards, or don't even finish at all. This is especially the case for large and complex projects with large differences between the parties involved. Although there is much knowledge and experience on what the causes are of sub-optimal project performance, this knowledge is still rather experential and anecdotal. In this paper, we will present a systematic approach towards building knowledge on factors influencing multi-site project behaviour. For this purpose, we will consider projects as temporary organisations. We will identify three classes of problems, which may lead to project failure. The paper addresses part of the causes of problems, namely differences between project parties. Our research focuses on new product development projects performed at multiple sites. A model will be presented of essential classes of differences to take into account in managing a project. In addition, a learning approach towards supporting project management in identifying and managing differences will be presented. The approach is illustrated with examples from a longitudinal case study into Dutch-Mexican collaborative projects.