La Polledrara di Cecanibbio (Rome, Italy), an example of protection and enhancement of a geosite of palaeontological and archaeological interest.

The middle Pleistocene site of La Polledrara di Cecanibbio, (NW of Rome, Italy), dated to about 300.000 years BP, is listed as one of Latium geosites. It was excavated since1985 and investigations are presently being completed. Two main depositional phases have been recognized at this site: an older one represented by a fluvial episode indicated by a segment of an ancient river bed where innumerable faunal remains (over 20,000), mainly referable to large mammals (Palaeoloxodon antiquus, Bos primigenius, Cervus elaphus, etc.), were found. During the second phase, the area became marshy; recent excavations in these levels uncovered the remains of an elephant, trapped in the mud, that had been exploited by humans (Homo heidelbergensis) as indicated by numerous lithic artifacts, used for butchering, recovered around the carcass. The archaeological deposit has been protected by a museum structure for its preservation and safeguard, allowing also enjoyment by a wider public

A Prospective, Multi Center Phase II Study Evaluating Predictive Factors for Lenalidomide Treatment in Relapse or Refractory Chronic Lymphocytic Leukemia Patients (LE.P.RE.): Preliminary Results about the First 20 Enrolled Patients

The aims of LE.P.RE. study include the identification of clinical and biological factors associated with clinical response and toxicity of lenalidomide monotherapy in relapsed/refractory CLL patients enrolled from 9 Italian centers. Lenalidomide treatment schedule starts with 5 mg daily and increases of 5 mg daily every two weeks, up to 25 mg daily or maximum tolerated dose. Therapy is scheduled to be administered for 12 courses (1 course = 4 weeks) unless disease progression or excessive toxicity are observed. Here we show preliminary results about the first 20 enrolled patients up to the 4th treatment course. Patients received a mean daily lenalidomide dose of 8 mg in the 1st course, 10 mg in the 2nd, 14 mg in the 3rd and 4th. Four patients left the study at the 1st course (1 acute renal failure ARF, 1 infection, 1 second neoplasia likely related to CLL, 1 consent withdrawal) and 3 patients at the 3rd (1 Tumor Flare Reaction TFR, 1 infection, 1 thrombocytopenia). The observed toxicities are listed in Table 1. After the 4th course, 13 patients were evaluable for response: 9 partial response (PR), 3 progressive disease (PD) and 1 stable disease (SD) [ORR 69%]. View this table: [in this window] [in a new window] Table 1 Hematological and extra hematological toxicities (n° tot cases=20) We compared the levels of several cytokines measured by ELISA in plasma of the 20 patients at baseline and day+8 of therapy. We observed a significant increase of IL2 Receptor (mean 55,31 vs 112,14 ng/ml; p<0,001), IL2 (14,15 vs 17,27 pg/ml; p=0,019), CCL3 (5,21 vs 21,23 pg/ml; p<0,001), CCL4 (24,76 vs 72,99 pg/ml; p=0,003), IL10 (2,65 vs 6,33 pg/ml; p=0,001), IL1b (0,94 vs 2,77 pg/ml; p=0,048), TNFa (35,00 vs 140,59 pg/ml; p<0,001) and IL8 (0,31 vs 3,50 pg/ml; p=0,037) and a decrease of Thrombospondin 1 (693 vs 488 ng/ml; p=0,037). Interestingly, we found that IL1b level decreased from baseline to day+8 in the 4 non responder (PD+SD) patients while increasing in the 9 responder (PR) patients. Moreover, we found that the 5 patients that experienced TFR or tumor lysis syndrome TLS had significantly higher CCL3 level at baseline than the other 15 patients (p=0,025). We also studied peripheral blood cell subsets (T, B, NK, monocyte, dendritic and endothelial cells) in the 20 patients by flow cytometry. From baseline to day+8 we observed a significant increase of the Thelper1/Thelper2 ratio (p<0,001), T cytotoxic1/Tcytotoxic2 ratio (p=0,001) and memory T cells % (p<0,001) as well as a decrease of naïve T cells % (p<0,001) and mean CD69 expression on T cells (p=0,016). Moreover, the expression of CD40 (p=0,001), CD80 (p=0,018), CD86 (p=0,003) and CD95 (p=0,008) were found to be increased on B-CLL cells. Finally, we observed a decrease of endothelial progenitors cells (EPC) (p=0,032) and live circulating endothelial cells (CEC) (p<0,001) and an increase of dead CEC (p<0,001). Interestingly, there was a significant difference in activated CEC (mean 53,57 vs 81,63 CEC %; p=0,031) and resting CEC (46,54 vs 18,37; p=0,031) at baseline between responders and non responders, respectively. Moreover, the patients exhibiting TFR or TLS showed a higher % of CD4+CD3+ cells (p=0,009) and CD4+CD8+ cells (p=0,036) at day+8 than the others. In conclusion: (i) the increase of inflammatory cytokines IL2R, IL2, CCL3, CCL4, IL10, IL1b and TNFa observed from baseline to day+8 suggests that lenalidomide can induce immune activation; (ii) the augmentation of IL2, IL2R and memory T cells and the decrease of naïve T cells noticed from baseline to day+8 indicate that lenalidomide can promote T cell activation; (iii) the shift toward Thelper1 and Tcytotoxic1 phenotypes and the increased expression of co-stimulatory molecules on B-CLL cells observed from baseline to day+8 suggest that lenalidomide can promote an active T cell response against leukemic cells; (iv) the alterations in EPC and CEC noticed from baseline to day+8 suggest that lenalidomide may also have an anti angiogenic action. Moreover, our preliminary data seem to show interesting biological differences among CLL patients that respond or do not respond to lenalidomide treatment, which if replicated in additional patients and with increasing time on therapy could give important information for predicting which patients may best respond to therapy or may experience TFR or TLS

First detection of the Crab Nebula at TeV energies with a Cherenkov telescope in a dual-mirror Schwarzschild-Couder configuration: the ASTRI-Horn telescope

International audienceWe report on the first detection of very high-energy gamma-ray emission from the Crab Nebula by a Cherenkov telescope in dual-mirror Schwarzschild-Couder (SC) configuration. This result has been achieved by means of the 4 m ASTRI-Horn telescope, operated on Mt. Etna, Italy, and developed in the context of the Cherenkov Telescope Array Observatory preparatory phase. The dual-mirror SC design is aplanatic and characterized by a small plate scale, which allows us to implement large cameras with a large field of view, with small-size pixel sensors and a high level of compactness. The curved focal plane of the ASTRI camera is covered by silicon photo-multipliers, managed by an unconventional front-end electronic system that is based on a customized peak-sensing detector mode. The system includes internal and external calibration systems, hardware and software for control and acquisition, and the complete data archiving and processing chain. These observations of the Crab Nebula were carried out in December 2018 during the telescope verification phase for a total observation time (after data selection) of 24.4 h, equally divided between on- and off-axis source exposure. The camera system was still under commission and its functionality was not yet completely exploited. Furthermore, due to recent eruptions of the Etna Volcano, the mirror reflection efficiency was reduced. Nevertheless, the observations led to the detection of the source with a statistical significance of 5.4σ above an energy threshold of ∼3 TeV. This result provides an important step toward the use of dual-mirror systems in Cherenkov gamma-ray astronomy. A pathfinder mini-array based on nine ASTRI-like telescopes with a large field-of-view is in the course of implementation.Key words: gamma rays: general / telescopes / techniques: miscellaneous / methods: data analysis / supernovae: individual: Crab Nebula⋆ Corresponding authors: S. Lombardi ([email protected]), O. Catalano ([email protected]), and S. Scuderi ([email protected])

Galactic transient sources with the Cherenkov Telescope Array

International audienceA wide variety of Galactic sources show transient emission at soft and hard X-ray energies: low-mass and high-mass X-ray binaries containing compact objects (e.g., novae, microquasars, transitional millisecond pulsars, supergiant fast X-ray transients), isolated neutron stars exhibiting extreme variability as magnetars as well as pulsar wind nebulae. Although most of them can show emission up to MeV and/or GeV energies, many have not yet been detected in the TeV domain by Imaging Atmospheric Cherenkov Telescopes. In this paper, we explore the feasibility of detecting new Galactic transients with the Cherenkov Telescope Array (CTA) and the prospects for studying them with Target of Opportunity observations. We show that CTA will likely detect new sources in the TeV regime, such as the massive microquasars in the Cygnus region, low-mass X-ray binaries with low-viewing angle, flaring emission from the Crab pulsar-wind nebula or other novae explosions, among others. We also discuss the multi-wavelength synergies with other instruments and large astronomical facilities

Dark Matter Line Searches with the Cherenkov Telescope Array

International audienceMonochromatic gamma-ray signals constitute a potential smoking gun signature for annihilating or decaying dark matter particles that could relatively easily be distinguished from astrophysical or instrumental backgrounds. We provide an updated assessment of the sensitivity of the Cherenkov Telescope Array (CTA) to such signals, based on observations of the Galactic centre region as well as of selected dwarf spheroidal galaxies. We find that current limits and detection prospects for dark matter masses above 300 GeV will be significantly improved, by up to an order of magnitude in the multi-TeV range. This demonstrates that CTA will set a new standard for gamma-ray astronomy also in this respect, as the world's largest and most sensitive high-energy gamma-ray observatory, in particular due to its exquisite energy resolution at TeV energies and the adopted observational strategy focussing on regions with large dark matter densities. Throughout our analysis, we use up-to-date instrument response functions, and we thoroughly model the effect of instrumental systematic uncertainties in our statistical treatment. We further present results for other potential signatures with sharp spectral features, e.g.~box-shaped spectra, that would likewise very clearly point to a particle dark matter origin

Galactic transient sources with the Cherenkov Telescope Array

International audienceA wide variety of Galactic sources show transient emission at soft and hard X-ray energies: low-mass and high-mass X-ray binaries containing compact objects (e.g., novae, microquasars, transitional millisecond pulsars, supergiant fast X-ray transients), isolated neutron stars exhibiting extreme variability as magnetars as well as pulsar wind nebulae. Although most of them can show emission up to MeV and/or GeV energies, many have not yet been detected in the TeV domain by Imaging Atmospheric Cherenkov Telescopes. In this paper, we explore the feasibility of detecting new Galactic transients with the Cherenkov Telescope Array (CTA) and the prospects for studying them with Target of Opportunity observations. We show that CTA will likely detect new sources in the TeV regime, such as the massive microquasars in the Cygnus region, low-mass X-ray binaries with low-viewing angle, flaring emission from the Crab pulsar-wind nebula or other novae explosions, among others. We also discuss the multi-wavelength synergies with other instruments and large astronomical facilities

Galactic transient sources with the Cherenkov Telescope Array

International audienceA wide variety of Galactic sources show transient emission at soft and hard X-ray energies: low-mass and high-mass X-ray binaries containing compact objects (e.g., novae, microquasars, transitional millisecond pulsars, supergiant fast X-ray transients), isolated neutron stars exhibiting extreme variability as magnetars as well as pulsar wind nebulae. Although most of them can show emission up to MeV and/or GeV energies, many have not yet been detected in the TeV domain by Imaging Atmospheric Cherenkov Telescopes. In this paper, we explore the feasibility of detecting new Galactic transients with the Cherenkov Telescope Array (CTA) and the prospects for studying them with Target of Opportunity observations. We show that CTA will likely detect new sources in the TeV regime, such as the massive microquasars in the Cygnus region, low-mass X-ray binaries with low-viewing angle, flaring emission from the Crab pulsar-wind nebula or other novae explosions, among others. We also discuss the multi-wavelength synergies with other instruments and large astronomical facilities