1,721,465 research outputs found
Cytogenetic aspects of B- cell chronic lymphocytic leukemia: their correlation with clinical stage and different polyclonal mitogens
No full textBlood lymphocytes from 23 patients with B-cell chronic lymphocytic leukemia were stimulated with different mitogens (lipopolysaccharide from E coli, phorbol myristate acetate ester, Staphylococcus aureus, and phytohemagglutinin M form). Functional properties of stimulated cells (blastic transformation, mitotic index, cIg production, Ig secretion, and acid phosphatase positivity) were evaluated and correlated with the stage of disease and chromosomal findings. Early stages of the disease are characterized by a relatively homogeneous response to polyclonal B-cell and activators and by a restricted number of chromosomal aberrations. Advanced stages show a more heterogeneous pattern of response and a higher incidence of abnormal karyotypes suggesting an involvement of various subclonal lines
Analysis of uncertainties in compact plate-fin recuperators for microturbines
No full textThe current study aims to perform a stochastic analysis on microturbine compact recuperators to evaluate the impact of uncertainties in design parameters on their cost and volume, by using two different probabilistic approaches: Monte Carlo (MC) and Response Sensitivity Analysis (RSA). These two methods have been developed in Matlab® and then coupled with CHEOPE (Compact Heat Exchanger Optimisation and Performance Evaluation) software, which allows to analyze two different types of recuperators, used in microturbine applications: the furnace-brazed plate-fin type and the welded primary surface type. This paper focuses on an analysis of plate-fin type recuperators, for which the cost function adopted was tuned and verified in a previous study. Three main parameters of the recuperator have been considered as uncertain: effectiveness, hot side and cold side pressure drops. The uncertainties associated with these three parameters are based on industrial knowledge. The aforementioned stochastic methods have been used to propagate such uncertainties on the relevant outputs, such as cost and volume, allowing us to evaluate the least expensive and the most compact recuperator among those analysed
Response to ibrutinib of a refractory IgA lymphoplasmacytic lymphoma carrying the MYD88 L265P gene mutation.
No full textIntroduction. Lymphoplasmacytic lymphoma (LPL) is characterised by the proliferation of B
lymphocytes with varying degrees of plasmacytic differentiation involving bone marrow (BM), lymph
nodes or spleen. Waldenstrom macroglobulinemia (WM) is a subset of LPL in which the malignant clone
produces IgM paraprotein. LPL patients with IgA/IgG paraprotein account for less than 5% of LPLs.
MYD88 mutation triggers survival through BTK activation in WM, a disease responding to ibrutinib,
whereas nonIgM LPL has not been extensively investigated at the molecular level.
Case report. In 2014 a 66 yearold woman presented with symptomatic anaemia (Haemoglobin, Hb: 9
g/dl), with IgAk monoclonal spike (1.6 g/dl) (Figure 1) and an otherwise unremarkable serum chemistry
profile. A BM biopsy showed an 80% infiltrate by lymphocytes and lymphoplasmacytoid cells. A
computed tomography (CT) scan documented neither adenopathy nor splenomegaly. Diagnosis of IgAsecreting
LPL was made. The patient was treated with rituximabcyclophosphamidedexamethasone
(RCD) with minor response (Figure 1). Eighteen months later she presented with progressive disease
(Hb 8 g/dl, IgAk monoclonal spike 1.9 g/dl). After 5 cycles of bendamustine, the BM aspirate showed
90% lymphoid cells. Adenopathies, splenomegaly and ascites were noted on a CT scan. After 3 cycles
of cyclophosphamidedoxorubicinvincristineprednisone (CHOP) our patient developed
thrombocytopenia (Platelets, PLT: 30x10^9/L), transfusiondependent anaemia (Hb 7.7 g/dl) and clinical
deterioration (Figure 1). We performed genetic studies of peripheral blood lymphocytes with a targeted
NGS approach detecting mutations in 20 genes frequently mutated in CLL (ATM, BIRC3, BRAF,
CDKN2A, PTEN, CDH2, DDX3X, FBXW7, KIT, KLHL6, KRAS, MYD88, NOTCH1, NRAS, PIK3CA,
POT1, SF3B1, TP53, XPO1, ZMYM3). Given the identification of MYD88 L265P mutation in the
peripheral blood, ibrutinib appeared a reasonable option. In February 2018 our patient started ibrutinib
420 mg/die (Figure 1). Hb and PLT improved from day +35 (Hb 1012 g/dl, PLT > 100x10^9/L). In July
2018 no ascites and 50% reduction of adenopathies and spleen were shown on a CT scan. In April
2019 the patient was still on full dose ibrutinib with transfusion independence and good performance
status.
Conclusion. To the best of our knowledge this is the first case of response to ibrutinib in a refractory IgA
LPL with MYD88 mutation
RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: CHEMOIMMUNOTHERAPY, TREATMENT UNTIL PROGRESSION WITH MECHANISM-DRIVEN AGENTS OR FINITE-DURATION THERAPY?
Full text linkTreatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) has dramatically improved thanks to the development of mechanism-driven agents including drugs that inhibit kinases in the BCR pathway or BCL2. The treating physician has now the opportunity to decide i) which patient can be still offered chemoimmunotherapy as salvage treatment, ii) which patient is a candidate to receiving at relapse continuous treatment with ibrutinib, idelalisib and rituximab or venetoclax and iii) which patient may benefit from a fixed-duration treatment using the BCL2 antagonist venetoclax in association with rituximab.
Ibrutinib is the most actively investigated drug in R/R CLL and data at a 7-year follow-up were reported, showing durable efficacy and favorable efficacy profile. The patients with cardiac disease, hypertension and on anticoagulant therapy are not ideal candidates for continuous therapy with this agent. Idelalisib and rituximab was tested in patients with unfavorable characteristics including cytopenias. The short follow-up and treatment emergent adverse events limit its role to patients unlikely to get a benefit with other agents. Venetoclax and rituximab is the only effective chemo-free approach for the treatment of R/R with a fixed duration (up to 24 months) schedule capable of inducing deep responses in the majority of cases with a reassuring safety profile.
While a deep knowledge of the growing body of scientific evidence is required to inform and guide the appropriate treatment choice and management, physicians cannot disregard the growing problem of sustainabilit
Immunophenotypic heterogeneity of mesenchymal stromal cells
No full textThe immunophenotypic analysis of ex vivo-expanded mesenchymal stromal cells (MSC) has so far been confined to single or dual staining analysis in normal subjects. In this study, using a four-color cytofluorimetric protocol, we demonstrated that cultured MSC derived from the bone marrow of patients with hematologic malignancies showed alterations in the expression of CD105, CD90, CD184, and HLA-DR molecules. The decrease in the percentage of CD105+ and CD90+ MSC correlated with an increased bone marrow angiogenesis. This paper provides evidence that multiparametric flow cytometry is essential for the establishment of a standardized protocol to identify various MSCs subsets and aberrant phenotypes
Gas turbine size optimization in a hybrid system considering SOFC degradation
No full textThe coupling of a pressurized solid oxide fuel cell (SOFC) and a gas turbine has been proven to result in extremely high efficiency and reduced emissions. The presence of the gas turbine can improve system durability compared to a standalone SOFC, because the turbomachinery can supply additional power as the fuel cell degrades to meet the power request. Since performance degradation is an obstacles to SOFC systems commercialization, the optimization of the hybrid system to mitigate SOFC degradation effects is of great interest. In this work, an optimization approach was used to innovatively study the effect of gas turbine size on system durability for a 400 kW fuel cell stack. A larger turbine allowed a bigger reduction in SOFC power before replacing the stack, but increased the initial capital investment and decreased the initial turbine efficiency. Thus, the power ratio between SOFC and gas turbine significantly influenced system economic results.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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