Coded Raman distributed temperature sensor using gain controlled EDFA

Orientadores: Fabiano Fruett, João Batista RosolemDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de ComputaçãoResumo: Nesse trabalho apresentamos o estudo do uso de amplificadores do tipo EDFA (Erbium Dopped Fiber Amplifier) em aplicações de sensores distribuídos de temperatura (DTS) baseados no efeito Raman operando com codificação. Pretende-se com o uso dessa técnica aumentar o de-sempenho do sistema de medição de temperatura distribuída, através da melhoria do alcance e da resolução de temperatura do sistema. Primeiramente mostramos uma visão geral de sensores a fibra optica, apresentando as principais características, aplicações, vantagens e limitações além das técnicas de medição mais utilizadas para esse tipo de sensor. Em seguida, apresentamos uma bre-ve revisão do espalhamento Raman em fibras ópticas como base para o entendimento dos sensores distribuídos de temperatura que utilizam esse efeito como mecanismo de funcionamento. Discu-timos a necessidade do uso de técnicas de processamento digital de sinais para diminuição de ruído na implementação de um sensor distribuído de temperatura baseado no efeito Raman, atra-vés da exploração da baixa potência do sinal retroespalhado anti-Stokes. Também mostramos, através de simulações, dois métodos usados para diminuir o ruído desses sinais, sendo eles o mé-todo das médias e o método Scode. Mostramos, em seguida, o uso de EDFAs em conjunto com a técnica de codificação Simplex code, com foco na distorção dos sinais devido ao transiente do EDFA. Estudamos a mitigação desse efeito de forma experimental. Realizamos a comparação entre sensores distribuídos de temperatura operando de modo tradicional (pulso único) e codifi-cado (Simplex code) sem o uso de EDFA, nesse caso alcançamos uma extensão no alcance de cerca de 7.5 dB (12,2 km) e uma melhoria na resolução de temperatura de 100°C@5 km. Por fim, comparamos o sensor de temperatura distribuído operando com codificação (Simplex code) com e sem EDFA, usando o amplificador obtivemos uma extensão no alcance de 4 dB (6,5 km) e uma melhoria na resolução de temperatura de 30°C@10 kmAbstract: In this work we present the study of the use of EDFA (Erbium Doped Fiber Amplifier) in a coded distributed temperature sensor (DTS) based on the Raman effect. The aim of this technique is to increase the performance of the distributed temperature measurement system by improving the range and temperature resolution. First, we show an overview of fiber optic sensors, presenting the main characteristics, applications, advantages and limitations besides the measurement tech-niques most used for this type of sensor. Next, we present a brief review of Raman scattering in optical fibers as a basis for the understanding of distributed temperature sensors that use this effect as a mechanism of operation. We discuss the need to use digital signal processing techniques to reduce noise in the implementation of a distributed Raman effect temperature sensor by exploiting the low power of the anti-Stokes backscatter signal. We also show, through simulations, two meth-ods used to reduce the noise of these signals, being the method of the means and the method Scode. We show the use of EDFAs with the Simplex code technique, focusing on signal distortion due to EDFA transient effect. We studied the mitigation of this effect experimentally. We performed the comparison between distributed temperature sensors operating in traditional (single pulse) and coded (Simplex code) mode without the use of EDFA, in this case, we reached an extension in the range about 7.5 dB (12.2 km) and an improvement in the temperature resolution of 100°C@10km. Finally, we compared the distributed temperature sensor operating with Simplex code with and without EDFA, using the amplifier we obtained an extension in the range of 4 dB (6.5 km) and an improvement in the temperature resolution of 30°C@10kmMestradoEletrônica, Microeletrônica e OptoeletrônicaMestre em Engenharia Elétric

Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice : results from the NEUF study

Altres ajuts: Amgen (Europe) GmbHThis retrospective observational study (NEUF) included adult patients with B-cell acute lymphoblastic leukemia (B-cell ALL) who had received blinatumomab for the treatment of minimal residual disease-positive (MRD+) or relapsed/refractory (R/R) B-cell ALL via an expanded access program (EAP). Patients were eligible if blinatumomab was initiated via the EAP between January 2014 and June 2017. Patients were followed from blinatumomab initiation until death, entry into a clinical trial, the end of follow-up, or the end of the study period (December 31, 2017), whichever occurred first. Of the 249 adult patients included, 109 were MRD+ (83 Philadelphia chromosome-negative [Ph−] and 26 Philadelphia chromosome-positive [Ph+]) and 140 had a diagnosis of R/R B-cell ALL (106 Ph− and 34 Ph+). In the MRD+ group, within the first cycle of blinatumomab treatment, 93% (n = 49/53) of Ph− and 64% (n = 7/11) of Ph+ patients with evaluable MRD achieved an MRD response (MRD <0.01%). Median overall survival (OS) was not reached over a median follow-up time of 18.5 months (Ph−, 18.8 [range: 5.1-34.8] months; Ph+, 16.5 [range: 1.8-31.6] months). In the R/R group, within two cycles of blinatumomab, 51% of Ph− and 41% of Ph+ patients achieved complete hematologic remission (CR/CRh/CRi), and 83% of Ph− and 67% of Ph+ MRD-evaluable patients in CR/CRh/CRi achieved an MRD response. Median (95% confidence interval) OS was 12.2 (7.3-24.2) months in the R/R Ph− subgroup and 16.3 (5.3-not estimated) months in the R/R Ph+ subgroup. This large, real-world data set of adults with B-cell ALL treated with blinatumomab confirms efficacy outcomes from published studies

Early peripheral clearance of leukemia-associated immunophenotypes in AML: centralized analysis of a randomized trial

Although genetics is a relevant risk factor in acute myeloid leukemia (AML), it can be minimally informative and/or not readily available for the early identification of patients at risk for treatment failure. In a randomized trial comparing standard vs high-dose induction (ClinicalTrials.gov 64NCT00495287), we studied early peripheral blast cell clearance (PBC) as a rapid predictive assay of chemotherapy response to determine whether it correlates with the achievement of complete remission (CR), as well as postremission outcome, according to induction intensity. Individual leukemia-associated immunophenotypes (LAIPs) identified pretherapy by flow cytometry were validated and quantified centrally after 3 days of treatment, expressing PBC on a logarithmic scale as the ratio of absolute LAIP1 cells on day 1 and day 4. Of 178 patients, 151 (84.8%) were evaluable. Patients in CR exhibited significantly higher median PBC (2.3 log) compared with chemoresistant patients (1.0 log; P&lt;.0001). PBC&lt;1.0 predicted the worst outcome (CR, 28%). With 1.5 log established as the most accurate cutoff predicting CR, 87.5% of patients with PBC .1.5 (PBChigh, n = 96) and 43.6% of patients with PBC 641.5 (PBClow, n = 55) achieved CR after single-course induction (P&lt;.0001). CR and PBChigh rates were increased in patients randomized to the high-dose induction arm (P 5 .04) and correlated strongly with genetic/cytogenetic risk. In multivariate analysis, PBC retained significant predictive power for CR, relapse risk, and survival. Thus, PBC analysis can provide a very early prediction of outcome, correlates with treatment intensity and disease subset, and may support studies of customized AML therapy

Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience

The addition of venetoclax to hypomethylating agents (HMA-V) improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive treatment. The aim of our study was to confirm data reported in literature, in a real-life multicenter experience. We retrospectively evaluated 56 naive AML patients who received HMA-V at 8 different collaborating Hematology Units in the North-East of Italy, from September 2018 to October 2020. Patients received azacitidine or decitabine at standard dose, adding venetoclax starting from cycle 1-3. The median time-to-response was 2 cycles and composite complete remission rate (CCR) was 67.9%. Thirteen out of 38 responders (34.2%) relapsed, with a median response duration of 13.7 months. Transfusion independence (TI) was obtained in 27 (87.0%) and 28 (90.3%) out of 31 patients for red blood cells and platelets, respectively. Median OS was 12.3 months (95% CI, 8.1-16.5), and median PFS was 11.3 months (95% CI, 4.6-17.9). Cytogenetic risk was the only variable impacting on survival, while no differences were observed stratifying patients by age, bone marrow blasts, WHO classification or type of HMA. In conclusion, our real-life multicenter experience indicates that HMA-V treatment allows achieving good response rates in naive AML patients, ineligible for intensive chemotherapy

Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults

BACKGROUND: Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.METHODS: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.RESULTS: Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1 plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).CONCLUSIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.)

14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia

Acute leukemias (ALs) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by coexpression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML, M0 or M1), T/myeloid mixed-phenotype acute leukemia (T/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32/BCL11B are the cytogenetic hallmark of this entity. In our screening of 915 hematological malignancies, there were 202 AML and 333 T-cell acute lymphoblastic leukemias (T-ALL: 58, ETP; 178, non-ETP; 8, T/M MPAL; 89, not otherwise specified). We identified 20 cases of immature leukemias (4% of AML and 3.6% of T-ALL), harboring 4 types of 14q32/BCL11B translocations: t(2,14)(q22.3;q32) (n = 7), t(6;14)(q25.3;q32) (n = 9), t(7;14)(q21.2;q32) (n = 2), and t(8;14)(q24.2;q32) (n = 2). The t(2;14) produced a ZEB2-BCL11B fusion transcript, whereas the other 3 rearrangements displaced transcriptionally active enhancer sequences close to BCL11B without producing fusion genes. All translocations resulted in the activation of BCL11B, a regulator of T-cell differentiation associated with transcriptional corepressor complexes in mammalian cells. The expression of BCL11B behaved as a disease biomarker that was present at diagnosis, but not in remission. Deregulation of BCL11B co-occurred with variants at FLT3 and at epigenetic modulators, most frequently the DNMT3A, TET2, and/or WT1 genes. Transcriptome analysis identified a specific expression signature, with significant downregulation of BCL11B targets, and clearly separating BCL11B AL from AML, T-ALL, and ETP-ALL. Remarkably, an ex vivo drug-sensitivity profile identified a panel of compounds with effective antileukemic activity

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings