A 1 mm Scintillating Fibre Tracker Readout by a Multi-anode Photomultiplier

This note describes a prototype particle tracking detector constructed with 1 mm plastic scintillating fibres with a 64 channel Hamamatsu H8500 flat-panel multi-anode photomultiplier readout. Cosmic ray tracks from an array of 11 gas-filled drift tubes were matched to signals in the scintillating fibres in order to measure the resolution and efficiency of tracks reconstructed in the fibre-based tracker. A GEANT4 detector simulation was also developed to compare cosmic ray data with MC results and is discussed in the note. Using the parameters measured in this experimental setup, modified fibre tracker designs are suggested to improve resolution and efficiency in future prototypes to meet modern detector specifications.Comment: Laboratori Nazionali Di Frascati SIDS-Pubblicazioni LNF - 10 / 21(P) October 26, 201

Optical Link of the Atlas Pixel Detector

The on-detector optical link of the ATLAS pixel detector contains radiation-hard receiver chips to decode bi-phase marked signals received on PIN arrays and data transmitter chips to drive VCSEL arrays. The components are mounted on hybrid boards (opto-boards). We present results from the irradiation studies with 24 GeV protons up to 32 Mrad (1.2 x 10^15 p/cm^2) and the experience from the production.Comment: 9th ICATPP Conference, Como, Ital

VFAT2: A front-end system on chip providing fast trigger information, digitized data storage and formatting for the charge sensitive readout of multi-channel silicon and gas particle detectors

The architecture, key design parameters and results for a highly integrated front-end readout system fabricated as a single ASIC are presented. The chip (VFAT2) comprises complex analog and digital functions traditionally designed as separate components. VFAT2 contains very low noise 128 channel front-end amplification with programmable internal calibration, intelligent “fast OR” trigger building outputs, digital data tagging and storage, data formatting and data packet transmission with error protection. VFAT2 is designed to work in the demanding radiation environments posed by modern H.E.P. experiments and in particular the TOTEM experiment of the LHC. Measured results are presented demonstrating full functionality and excellent analog performance despite intensive digital activity on the same piece of silicon

Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, distinct subtype of T-ALL characterized by genomic instability, a dismal prognosis and refractoriness to standard chemotherapy. Since its first description in 2009, the expanding knowledge of its intricate biology has led to the definition of a stem cell leukemia with a combined lymphoid-myeloid potential: the perfect trick. Several studies in the last decade aimed to better characterize this new disease, but it was recognized as a distinct entity only in 2016. We review current insights into the biology of ETP-ALL and discuss the pathogenesis, genomic features and their impact on the clinical course in the precision medicine era today

Can the new and old drugs exert an immunomodulatory effect in acute myeloid leukemia?

Acute myeloid leukemia (AML) is considered an immune-suppressive neoplasm capable of evading immune surveillance through cellular and environmental players. Increasing knowledge of the immune system (IS) status at diagnosis seems to suggest ever more attention of the crosstalk between the leukemic clone and its immunologic counterpart. During the last years, the advent of novel immunotherapeutic strategies has revealed the importance of immune dysregulation and suppression for leukemia fitness. Considering all these premises, we reviewed the “off-target” effects on the IS of different drugs used in the treatment of AML, focusing on the main advantages of this interaction. The data reported support the idea that a successful therapeutic strategy should consider tailored approaches for performing leukemia eradication by both direct blasts killing and the engagement of the IS

FLT3 mutational analysis in acute myeloid leukemia: Advantages and pitfalls with different approaches

FMS-like tyrosine kinase 3 (FLT3) is one of the most closely studied genes in blood diseases. Numerous methods have been adopted for analyses, mainly in acute myeloid leukemia (AML) diagnostic work-up. According to international recommendations, the current gold standard approach allows FLT3 canonical mutations to be investigated, providing the main information for risk assessment and treatment choice. However, the technological improvements of the last decade have permitted “black side” gene exploration, revealing numerous hidden aspects of its role in leukemogenesis. The advent of the next-generation sequencing era emphasizes lights and shadows of FLT3 conventional mutational analysis, highlighting the need for a more comprehensive study of the gene. However, more extensive analysis is opening new, unexplored questions whose impact on clinical outcomes is still unknown. The present work is focused on the main topics regarding FLT3 mutational analysis in AML, debating the strengths and weaknesses of the current gold standard approach. The rights and wrongs of NGS introduction in clinical practice will be discussed, showing that a more extensive knowledge of FLT3 mutational status could lead to reconsidering its role in AML management

Mitochondrial Content and Hepcidin are Increased in Obese Pregnant Mothers

OBJECTIVE: Maternal obesity is characterized by systemic low-grade inflammation and oxidative stress (OxS) with the contribution of fetal sex dimorphism. We recently described increased mitochondrial content (mtDNA) in placentas of obese pregnancies. Here, we quantify mtDNA and hepcidin as indexes of OxS and systemic inflammation in the obese maternal circulation. METHODS: Forty-one pregnant women were enrolled at elective cesarean section: 16 were normal weight (NW) and 25 were obese (OB). Obese women were further classified according to the presence/absence of maternal gestational diabetes mellitus (GDM); [OB/GDM(-)]: n\u2009=\u200915, [OB/GDM(+)]: n\u2009=\u200910. mtDNA and hepcidin were evaluated in blood (real-time PCR) and plasma (ELISA). RESULTS: mtDNA and hepcidin levels were significantly increased in OB/GDM(-) versus NW, significantly correlating with pregestational BMI. Male/female (M/F) ratio was equal in study groups, and overall F-carrying pregnancies showed significantly higher mtDNA and hepcidin levels than M-carrying pregnancies both in obese and normal weight mothers. CONCLUSIONS: Our results indicate a potential compensatory mechanism to increased obesity-related OxS and inflammation, indicated by the higher hepcidin levels found in obese mothers. Increased placental mitochondrial biogenesis, due to lipotoxic environment, may account for the greater mtDNA amount released in maternal circulation. This increase is namely related to F-carrying pregnancies, suggesting a gender-specific placental response

Nanopore Sequencing in Blood Diseases: A Wide Range of Opportunities

The molecular pathogenesis of hematological diseases is often driven by genetic and epigenetic alterations. Next-generation sequencing has considerably increased our genomic knowledge of these disorders becoming ever more widespread in clinical practice. In 2012 Oxford Nanopore Technologies (ONT) released the MinION, the first long-read nanopore-based sequencer, overcoming the main limits of short-reads sequences generation. In the last years, several nanopore sequencing approaches have been performed in various “-omic” sciences; this review focuses on the challenge to introduce ONT devices in the hematological field, showing advantages, disadvantages and future perspectives of this technology in the precision medicine era