The Role of Meningioma-1 (Mn1) Gene as Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: A Concise Review

Molecular markers are necessary for prognostic stratification and monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML) [1,2]. Cytogenetic aberrations have long been recognized as the most important prognostic variable in AML, and are still the major determinant for post-remission therapy [3]. Unfortunately, only 50-60% of AML patients present an abnormal karyotype at diagnosis, while the remaining cases display a Normal Karyotype (NK). NK AML patients are generally included in an “intermediate risk” prognostic group, that is however characterized by a heterogeneous clinical course. To stratify prognosis of NK AML patients, numerous studies have led, in the last decade, to the introduction of different molecular markers such as FLT3, NPM1, BAALC and CEBPA [4-7]. Still, their use to monitor disease, either defining remission status and detecting relapse as early as possible, is still somehow controversial, due to fluctuations during disease course, low incidence rates in AML and sensitivity of the technologies detecting the single marker [8-10]. These limitations have, to date, precluded a timely and precise quantification of disease in NK AML patients, thus preventing from a complete individualization of post-remission therapy and early treatment in case of impending relapse. In other words, in NK AML it has not been reached the precision achieved in BCR/ABL-positive chronic myeloid leukemia and PML/RAR alpha mutated acute promyelocytic leukemia

Predictive value of pretransplantation molecular minimal residual disease assessment by WT1 gene expression in FLT3-positive acute myeloid leukemia

The FMS-like tyrosine kinase 3 (FLT3) mutation in acute myeloid leukemia (AML) is a negative prognostic factor and, in these cases, allogeneic stem cell transplantation (allo-SCT) can represent an important therapeutic option, especially if performed in complete remission (CR). However, it is increasingly clear that not all cytological CRs (cCRs) are the same and that minimal residual disease (MRD) before allo-SCT could have an impact on AML outcome. Unfortunately, FLT3, due its instability of expression, is still not considered a good molecular MRD marker. We analyzed the outcome of allo-SCT in a population of FLT3-positive AML patients according to molecular MRD at the pretransplantation workup, assessed by the quantitative expression evaluation of the panleukemic marker Wilms\u2019 tumor (WT1) gene. Sixty-two consecutive AML FLT3-positive patients received allo-SCT between 2005 and 2016 in our center. The median age at transplantation was 55 years. The quantitative analysis of the WT1 gene expression (bone marrow samples) was available in 54 out of 62 (87%) cases, both at diagnosis (100% overexpressing WT1 with a mean of 9747 \ub1 8064 copies) and before allo-SCT (33 WT1-negative and 21 WT1-positive cases at the pretransplantation workup). Of these cases, 33/54 (61%) were both in cCR and molecular remission (WT1-negative) at the time of transplantation, 13/54 (24%) were in cCR but not in molecular remission (WT1-positive), and 8/54 (15%) showed a cytological evidence of disease (relapsed or refractory). Both post-allo-SCT overall survival (OS) and disease-free survival (DFS) were significantly better in patients who were WT1-negative (WT1 250 copies), with a median OS and DFS not reached in the WT1-negative group and 10.2 and 5.5 months, respectively, in the WT1-positive group (OS log\u2013rank p = 0.0005; hazard ratio [HR] = 3.7, 95% confidence interval [95% CI] = 1.5\u20139; DFS log\u2013rank p = 0.0001; HR = 4.38, 95% CI = 1.9\u201310). Patients with cCR who were WT1-positive had the same negative outcome as those with a cytological evidence of disease. The relapse rate after allo-SCT was 9% (3/33) in pre-allo-SCT WT1-negative cases and 54% (7/13) in WT1-positive cases (p = 0.002). At multivariate analysis, WT1 negativity before allo-SCT and grade <2 acute graft versus host disease were the only independent prognostic factors for improved OS and DFS. These data show that pre-allo-SCT molecular MRD evaluation through WT1 expression is a powerful predictor of posttransplantation outcomes (OS, DFS, relapse rate). Patients with both cCR and a WT1-negative marker before allo-SCT have a very good outcome with very low relapse rate; conversely, patients with positive molecular MRD and refractory/relapsed patients have a negative outcome. The WT1 MRD stratification in FLT3-positive AML is a valuable tool with which to identify patients who are at high risk of relapse and that could be considered from post-allo-SCT prophylaxis with FLT3 inhibitors or other strategies (donor lymphocyte infusion, tapering of immunosuppression, azacitidine). \ua9 2017 ISEH - International Society for Experimental Hematolog

Online Quantification of Criegee Intermediates of α-Pinene Ozonolysis by Stabilization with Spin Traps and Proton-Transfer Reaction Mass Spectrometry Detection

Biogenic alkenes, which are among the most abundant volatile organic compounds in the atmosphere, are readily oxidized by ozone. Characterizing the reactivity and kinetics of the first-generation products of these reactions, carbonyl oxides (often named Criegee intermediates), is essential in defining the oxidation pathways of organic compounds in the atmosphere but is highly challenging due to the short lifetime of these zwitterions. Here, we report the development of a novel online method to quantify atmospherically relevant Criegee intermediates (CIs) in the gas phase by stabilization with spin traps and analysis with proton-transfer reaction mass spectrometry. Ozonolysis of α-pinene has been chosen as a proof-of-principle model system. To determine unambiguously the structure of the spin trap adducts with α-pinene CIs, the reaction was tested in solution, and reaction products were characterized with high-resolution mass spectrometry, electron paramagnetic resonance, and nuclear magnetic resonance spectroscopy. DFT calculations show that addition of the Criegee intermediate to the DMPO spin trap, leading to the formation of a six-membered ring adduct, occurs through a very favorable pathway and that the product is significantly more stable than the reactants, supporting the experimental characterization. A flow tube set up has been used to generate spin trap adducts with α-pinene CIs in the gas phase. We demonstrate that spin trap adducts with α-pinene CIs also form in the gas phase and that they are stable enough to be detected with online mass spectrometry. This new technique offers for the first time a method to characterize highly reactive and atmospherically relevant radical intermediates in situ.This work was funded by the European Research Council (ERC starting grant 279405). Authors thank four anonymous reviewers for helpful revision of the manuscript

Finding footy : female fan socialization and Australian rules football

The question of how, irrespective of gender, a person becomes a sports fan has been absent in sociological studies of sports supporters. Distinct from other studies of sport spectatorship that focus on the practices of already existing (and overwhelmingly male) fans, our research is the first to consider how women become supporters, and in doing so, it begins to redress the significant under-representation of women in sports fan research. From interviews with female supporters of the Australian Football League (AFL), this article identifies and critically assesses the modes by which women come to support sport. We propose four categories to explain the different ways women accomplish fandom, focusing on the importance of strong social ties and doxic actions in this process. The events, experiences and social relations that inform women\u27s first encounters with AFL offers a template for the wider consideration of women as social agents in the sporting landscape

BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the “GRUPPO TRIVENETO LMC”

We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087

Acute rhabdomyolysis and delayed pericardial effusion in an Italian patient with Ebola virus disease : a case report

Background: During the 2013-2016 West Africa Ebola virus disease (EVD) epidemic, some EVD patients, mostly health care workers, were evacuated to Europe and the USA. Case presentation: In May 2015, a 37-year old male nurse contracted Ebola virus disease in Sierra Leone. After Ebola virus detection in plasma, he was medically-evacuated to Italy. At admission, rhabdomyolysis was clinically and laboratory-diagnosed and was treated with aggressive hydration, oral favipiravir and intravenous investigational monoclonal antibodies against Ebola virus. The recovery clinical phase was complicated by a febrile thrombocytopenic syndrome with pericardial effusion treated with corticosteroids for 10days and indomethacin for 2months. No evidence of recurrence is reported. Conclusions: A febrile thrombocytopenic syndrome with pericardial effusion during the recovery phase of EVD appears to be uncommon. Clinical improvement with corticosteroid treatment suggests that an immune-mediated mechanism contributed to the pericardial effusion

Children and objects: affection and infection

This paper considers young children’s (aged 3–5 years) relations with objects, and in particular objects that are brought from home to school. We begin by considering the place of objects within early years classrooms and their relationship to children’s education before considering why some objects are often separated from their owners on entry to the classroom. We suggest that the ‘arrest’ of objects is as a consequence of them being understood as ‘infecting’ specific perceptions or constructs of young children. We further suggest that a focus on the dichotomy between affection/infection for and of certain objects may offer new possibilities for seeing and engaging with children, thus expanding the narrow imaginaries of children that are coded in developmental psychology, UK early years education policy and classroom practice

I rapporti tra IPRs e antitrust : funzioni, ancoraggi, bilanciamenti

Il lavoro affronta la questione del rapporto tra antitrust e propriet\ue0 intellettuale, ricordando la casistica, dalle origini alle applicazioni recenti, e individuando il riifiuto di licenza come la fattispecie in cui la tensione tra le funzioni delle due discipline \ue8 pi\uf9 intensa. Propone poi di esaminare la questione nella prospettiva delle scriminanti dell'abuso, con il test contenuto nel par. 3 dell'art. 101 TFUE. In questa chiave, rilegge i leading case della Corte Europea (Volvo, Magill, IMS e Microsoft) come casi il cui esito \ue8 determinato dalla possibilit\ue0 di vedere verificati il criterio della "congrua riserva di utili per i consumatori" e della "non eliminazione della concorrenza" e conclude individuando una valutazione comparativa di interessi, e non un impersonale calcolo degli effetti netti di efficienza, come criterio alla base delle pronunce della Corte e degli orientamenti della Commissione