107 research outputs found
Book review: crashed: how a decade of financial crises changed the world by Adam Tooze (part 2)
No full textIn Crashed: How a decade of financial crises changed the world, author Adam Tooze proposes a remarkably consistent narrative of the 2008 financial crisis and its political, geopolitical consequences - one that attempts a coherent interpretation of the global and European crises. In part two of his review of this seminal work, Shahin Vallée examines Tooze's take on the crisis of transatlantic finance and the existential crisis for Europe that ensued
Book review: crashed: how a decade of financial crises changed the world by Adam Tooze (part 1)
No full textIn Crashed: How a decade of financial crises changed the world, author Adam Tooze proposes a remarkably consistent narrative of the 2008 financial crisis and its political, geopolitical consequences - one that attempts a coherent interpretation of the global and European crises. In part one of his review of this seminal work, Shahin Vallée examines Tooze's take on the collapse of the financial system, and saving the economy at the cost of our politics
RCRC on Mortgage Finance for the Energy Transition
No full textJoin Regenerative Crisis Response Committee members Sarah Bloom Raskin (former Fed Governor) Adam Tooze (Foreign Policy Magazine Thinker of the Decade) and Stephanie Kelton (Author of \u27The Deficit Myth\u27) for a lively discussion of the role changing the definition of the American conforming mortgage could have in accelerating the energy transition
Comparative analysis of gene expression platforms for cell‐of‐origin classification of diffuse large B‐cell lymphoma shows high concordance
No full textCell‐of‐origin subclassification of diffuse large B cell lymphoma (DLBCL) into activated B cell‐like (ABC), germinal centre B cell‐like (GCB) and unclassified (UNC) or type III by gene expression profiling is recommended in the latest update of the World Health Organization’s classification of lymphoid neoplasms. There is, however, no accepted gold standard method or dataset for this classification. Here, we compare classification results using gene expression data for 68 formalin‐fixed paraffin‐embedded DLBCL samples measured on four different gene expression platforms (Illumina wG‐DASLTM arrays, Affymetrix PrimeView arrays, Illumina TrueSeq RNA sequencing and the HTG EdgeSeq DLBCL Cell of Origin Assay EU using an established platform agnostic classification algorithm (DAC) and the classifier native to the HTG platform, which is CE marked for in vitro diagnostic use (CE‐IVD). Classification methods and platforms show a high level of concordance, with agreement in at least 80% of cases and rising to much higher levels for classifications of high confidence. Our results demonstrate that cell‐of‐origin classification by gene expression profiling on different platforms is robust, and that the use of the confidence value alongside the classification result is important in clinical applications
A Replicative Self-Renewal Model for Long-Lived Plasma Cells: Questioning Irreversible Cell Cycle Exit
No full textA replicative self-renewal model for long-lived plasma cells: Questioning irreversible cell cycle exit.
No full textPlasma cells are heterogenous in terms of their origins, secretory products and lifespan. A current paradigm is that cell cycle exit in plasma cell differentiation is irreversible, following a pattern familiar in short-lived effector populations in other haemopoietic lineages. This paradigm no doubt holds true for many plasma cells whose lifespan can be measured in days following the completion of differentiation. Whether this holds true for long-lived bone marrow plasma cells that are potentially maintained for the lifespan of the organism is less apparent. Added to this the mechanisms that establish and maintain cell cycle quiescence in plasma cells are incompletely defined. Gene expression profiling indicates that in the transition of human plasmablasts to long-lived plasma cells a range of cell cycle regulators are induced in a pattern that suggests a quiescence program with potential for cell cycle re-entry. Here a model of relative quiescence with the potential for replicative self-renewal amongst long-lived plasma cells is explored. The implications of such a mechanism would be diverse, and the argument is made here that current evidence is not sufficiently strong that the possibility should be disregarded
Malignant adenomyoepithelioma of the breast metastasizing to the liver [Letter to the Editor]
No full textDifferential Efficacy From the Addition of Bortezomib to R-CHOP in Diffuse Large B-Cell Lymphoma According to the Molecular Subgroup in the REMoDL-B Study With a 5-Year Follow-Up.
No full textClinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The REMoDL-B phase III adaptive trial compared rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) versus R-CHOP + bortezomib (RB-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL), stratified by molecular subtype. Primary analysis at a median follow-up of 30 months found no effect of bortezomib on progression-free survival (PFS) or overall survival (OS). Retrospective analysis using a gene expression-based classifier identified a molecular high-grade (MHG) group with worse outcomes. We present an updated analysis for patients successfully classified by the gene expression profile (GEP). Eligible patients were age older than 18 years with untreated DLBCL, fit enough for full-dose chemotherapy, and with adequate biopsies for GEP. Of 1,077 patients registered, 801 were identified with Activated B-Cell (ABC), Germinal Center B-cell, or MHG lymphoma. At a median follow-up of 64 months, there was no overall benefit of bortezomib on PFS or OS (5-year PFS hazard ratio [HR], 0.81; P = .085; OS HR, 0.86; P = .32). However, improved PFS and OS were seen in ABC lymphomas after RB-CHOP: 5-year OS 67% with R-CHOP versus 80% with RB-CHOP (HR, 0.58; 95% CI, 0.35 to 0.95; P = .032). Five-year PFS was higher in MHG lymphomas: 29% versus 55% (HR, 0.46; 95% CI, 0.26 to 0.84). Patients with ABC and MHG DLBCL may benefit from the addition of bortezomib to R-CHOP in initial therapy
Gene expression profiling in an open-label randomised phase 3 trial (REMoDL-B) of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma
No full textBackground: Biologically distinct sub-types of diffuse large B-cell lymphoma (DLBCL) can be identified using gene expression analysis to determine their cell of origin (COO), corresponding to germinal centre (GCB) or activated B‐cells (ABC). This study investigated whether adding bortezomib(B) to standard therapy could improve outcomes in these subtypes.Methods: The REMoDL-B trial is an open-label adaptive two-stage randomised controlled trial at 107 centres in the United Kingdom and Switzerland. Eligible patients (pts) had previously untreated, histologically confirmed DLBCL with sufficient diagnostic material for gene expression profiling and pathology review; age 18 years or older; Eastern Cooperative Oncology Group performance status of ≤2; bulky stage I or stage II-IV requiring full course chemotherapy; measurable disease, and cardiac, lung, renal and liver function sufficient to tolerate chemotherapy. Pts initially received 1 cycle of standard R‐CHOP. During this time, gene expression profiling by whole genome cDNA-mediated annealing, selection, extension and ligation assay was performed on routine diagnostic biopsy material. Patients were then centrally assigned (1:1) via a web-based system, with block randomisation stratified by international prognostic index and COO subtype to continue R‐CHOP +/‐ bortezomib (1.3 mg/m2 IV or 1.6 mg/m2 SC) days 1+8 for cycles 2‐6. The primary endpoint was 30 month progression‐free survival (PFS) for the GCB + ABC population. The primary analysis was intention-to-treat. The safety population consisted of all participants who received at least one dose of study drug. The study was registered at ClinicalTrials.gov: NCT01324596. We report the PFS and safety outcomes for patients in the follow-up phase after the required number of events occurred. Recruitment and treatment has completed for all participants, with long-term follow-up continuingFindings: Between June 2011 and June 2015, 1128 eligible pts were registered and a total of 918 randomised. There was no evidence for a difference in PFS in the combined GCB + ABC population between R‐CHOP (N=361)and RB‐CHOP (N=358) (30 month PFS: 70.6% vs 75.2% respectively) adjusted HR = 0.82, 95% CI 0.63 - 1.08; P=0.16. The most common Grade ≥3 adverse event experienced was haematological toxicity, with 178 (39.8%) and 187 (42.1%) of pts receiving R-CHOP and RB-CHOP experienced, respectively. However, RB‐CHOP was not associated with increased haematological toxicity and 87% of pts completed 6 cycles; Grade ≥3 neuropathy occurred in 3.8% RB‐CHOP vs 1.8% R‐CHOP pts. Serious adverse events occurred in 190 (42.5%) and 223 (50.2%) of pts, including 5 and 4 treatment-related deaths in pts receiving R-CHOP and RB-CHOP, respectively.Interpretation: This is the first large-scale study in DLBCL to use real-time molecular characterisation for prospective stratification and randomisation, and subsequent analysis of biologically distinct subgroups. The addition of bortezomib did not improve outcomes in the ABC subgroup as expected, but proteosome inhibition could be investigated as a possible means to improve the treatment of cytogenetic 'double-hit' DLBCL.Funding: Janssen-Cilag, Bloodwise and Cancer Research UK. <br/
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