New approaches to the management of adult acute lymphoblastic leukemia

Traditional treatment regimens for adult acute lymphoblastic leukemia, including allogeneic hematopoietic cell transplantation, result in an overall survival of about 40%, a figure hardly comparable with the extraordinary 80-90% cure rate currently reported in children. When translated to the adult setting, modern pediatric-type regimens improve the survival to about 60% in young adults. The addition of tyrosine kinase inhibitors for patients with Philadelphia chromosome positive disease and the measurement of minimal residual disease to guide risk stratification and post-remission approaches has led to further improvements in outcomes. Relapsed disease and treatment toxicity - sparing no patient but representing a major concern especially in the elderly - are the most critical current issues awaiting further therapeutic advancement. Recently, there has been considerable progress in understanding the disease biology, specifically the Philadelphia-like signature as well as other high-risk subgroups. In addition, there are several new agents that will undoubtedly contribute to further improvement in the current outcomes. The most promising agents are new the monoclonal antibodies, immunomodulators, and chimeric antigen receptor T cells and, to a lesser extent, several new drugs targeting key molecular pathways involved in leukemic cell growth and proliferation. This review examines the evidence supporting the increasing role of the new therapeutic tools and treatment options in different disease subgroups, including frontline and relapsed/refractory disease. It is now possible to define the best individual approach based on to the emerging concepts of precision medicine

Characteristics and energy dependence of recurrent galactic cosmic-ray flux depressions and of a forbush decrease with LISA Pathfinder

The final publication is available at IOS Press through http://dx.doi.org/10.3847/1538-4357/aaa774Galactic cosmic-ray (GCR) energy spectra observed in the inner heliosphere are modulated by the solar activity, the solar polarity and structures of solar and interplanetary origin. A high counting rate particle detector (PD) aboard LISA Pathfinder, meant for subsystems diagnostics, was devoted to the measurement of GCR and solar energetic particle integral fluxes above 70 MeV n-1 up to 6500 counts s-1. PD data were gathered with a sampling time of 15 s. Characteristics and energy dependence of GCR flux recurrent depressions and of a Forbush decrease dated 2016 August 2 are reported here. The capability of interplanetary missions, carrying PDs for instrument performance purposes, in monitoring the passage of interplanetary coronal mass ejections is also discussed.Peer ReviewedPreprin

Increasing the bandwidth of resonant gravitational antennas: The case of Explorer

Resonant gravitational wave detectors with an observation bandwidth of tens of hertz are a reality: the antenna Explorer, operated at CERN by the ROG collaboration, has been upgraded with a new read-out. In this new configuration, it exhibits an unprecedented useful bandwidth: in over 55 Hz about its frequency of operation of 919 Hz the spectral sensitivity is better than 10^{-20} /sqrt(Hz) . We describe the detector and its sensitivity and discuss the foreseable upgrades to even larger bandwidths.Comment: 4 pages- 4 figures Acceted for publication on Physical Review Letter

Optimizing the Earth-LISA "rendez-vous"

We present a general survey of heliocentric LISA orbits, hoping it might help in the exercise of rescoping the mission. We try to semi-analytically optimize the orbital parameters in order to minimize the disturbances coming from the Earth-LISA interaction. In a set of numerical simulations we include nonautonomous perturbations and provide an estimate of Doppler shift and breathing as a function of the trailing angle.Comment: 18 pages, 16 figures. Submitted on CQ

Reception frequency bandwidth of a gravitational resonant detector with optical readout

A gravitational resonant bar detector with a large scale Fabry-Perot cavity as an optical read out and a mechanical displacement transformer is considered. We calculate, in a fully analytical way, the final receiver bandwidth in which the potential sensitivity, limited only by the bar thermal noise, is maintained despite the additional thermal noise of the transformer and the additive noise of the optical readout. We discuss also an application to the OGRAN project, where the bar is instrumented with a 2m long FP cavity.Comment: 16 pages + 3 figures. Accepted for publicationi in Class. Quantum Gra

Dark Matter searches using gravitational wave bar detectors: quark nuggets and newtorites

Many experiments have searched for supersymmetric WIMP dark matter, with null results. This may suggest to look for more exotic possibilities, for example compact ultra-dense quark nuggets, widely discussed in literature with several different names. Nuclearites are an example of candidate compact objects with atomic size cross section. After a short discussion on nuclearites, the result of a nuclearite search with the gravitational wave bar detectors Nautilus and Explorer is reported. The geometrical acceptance of the bar detectors is 19.5 $\rm m^2$ sr, that is smaller than that of other detectors used for similar searches. However, the detection mechanism is completely different and is more straightforward than in other detectors. The experimental limits we obtain are of interest because, for nuclearites of mass less than $10^{-5}$ g, we find a flux smaller than that one predicted considering nuclearites as dark matter candidates. Particles with gravitational only interactions (newtorites) are another example. In this case the sensitivity is quite poor and a short discussion is reported on possible improvements.Comment: published on Astroparticle Physics Sept 25th 2016 replaced fig 1

Signatures of photon and axion-like particle mixing in the gamma-ray burst jet

Photons couple to Axion-Like Particles (ALPs) or more generally to any pseudo Nambu-Goldstone boson in the presence of an external electromagnetic field. Mixing between photons and ALPs in the strong magnetic field of a Gamma-Ray Burst (GRB) jet during the prompt emission phase can leave observable imprints on the gamma-ray polarization and spectrum. Mixing in the intergalactic medium is not expected to modify these signatures for ALP mass > 10^(-14) eV and/or for < nG magnetic field. We show that the depletion of photons due to conversion to ALPs changes the linear degree of polarization from the values predicted by the synchrotron model of gamma ray emission. We also show that when the magnetic field orientation in the propagation region is perpendicular to the field orientation in the production region, the observed synchrotron spectrum becomes steeper than the theoretical prediction and as detected in a sizable fraction of GRB sample. Detection of the correlated polarization and spectral signatures from these steep-spectrum GRBs by gamma-ray polarimeters can be a very powerful probe to discover ALPs. Measurement of gamma-ray polarization from GRBs in general, with high statistics, can also be useful to search for ALPs.Comment: 17 pages, 3 figures. Accepted for publication in JCAP with minor change

Impact of Dapagliflozin Adjunctive Therapy on Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes and CKD Stage 2–5: A systematic review and meta-analysis

This meta-analysis was conducted by searching PubMed, Scopus, Cochrane, Ovid till November 2022 for randomized controlled trials (RCTs) that utilized dapagliflozin 10 mg as adjunctive therapy in patients with T2DM and CKD stage 2-5 and reported its renal efficacy in terms of mean change in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) from baseline. From 1682 identified records, nine studies representing 13,057 patients were selected for this study. Pooled estimate of five studies showed that dapagliflozin did not affect eGFR but caused significantly less chronic eGFR decline than placebo in two studies [Mean difference (MD) +2.74 (95% CI: 1.55, 3.92; p &lt; 0.00001)]. Pooled estimate of four studies showed that dapagliflozin significantly reduced UACR[-23.99 % MD (95% CI - 34.82, -13.15, p-value &lt; 0.0001; = 0%)]. This confirms that long-term dapagliflozin use significantly attenuates eGFR decline and reduces albuminuria in T2DM and CKD stages 2-5 patients. Keywords: Chronic kidney disease, Dapagliflozin, Estimated GFR, eGFR, SGLT2 inhibitors, Type 2 diabetes mellitus, Urine albumin to creatinine ratio, UACR

Raman-based Distributed Temperature Sensor Using Simplex Code And Gain Controlled Edfa

In this work we present a comparison between simplex coded and optical amplified simplex coded Raman based Distributed Temperature Sensing (DTS). An increase in performance is demonstrated using erbium doped fiber amplifier (EDFA) with proper gain control scheme that allows a DTS operates with simplex code. Using 63-bit simplex code and gain controlled EDFA we demonstrated the temperature resolution and dynamic range improvement in 16 degrees C @ 10 km and 4 dB, respectively.963

Quark nuggets search using 2350 Kg gravitational waves aluminum bar detectors

The gravitational wave resonant detectors can be used as detectors of quark nuggets, like nuclearites (nuclear matter with a strange quark). This search has been carried out using data from two 2350 Kg, 2 K cooled, aluminum bar detectors: NAUTILUS, located in Frascati (Italy), and EXPLORER, that was located in CERN Geneva (CH). Both antennas are equipped with cosmic ray shower detectors: signals in the bar due to showers are continuously detected and used to characterize the antenna performances. The bar excitation mechanism is based on the so called thermo-acoustic effect, studied on dedicated experiments that use particle beams. This mechanism predicts that vibrations of bars are induced by the heat deposited in the bar from the particle. The geometrical acceptance of the bar detectors is 19.5 $\rm m^2$ sr, that is smaller than that of other detectors used for similar searches. However, the detection mechanism is completely different and is more straightforward than in other detectors. We will show the results of ten years of data from NAUTILUS (2003-2012) and 7 years from EXPLORER (2003-2009). The experimental limits we obtain are of interest because, for nuclearites of mass less than $10^{-4}$ grams, we find a flux smaller than that one predicted considering nuclearites as dark matter candidates.Comment: presented to the 33rd International Cosmic Ray Conference Rio de Janeiro 201