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])

A detailed study of the very-high-energy Crab pulsar emission with the LST-1

International audienceContext: There are currently three pulsars firmly detected by imaging atmospheric Cherenkov telescopes (IACTs), two of them reaching TeV energies, challenging models of very-high-energy (VHE) emission in pulsars. More precise observations are needed to better characterize pulsar emission at these energies. The LST-1 is the prototype of the Large-Sized Telescope, that will be part of the Cherenkov Telescope Array Observatory (CTAO). Its improved performance over previous IACTs makes it well suited for studying pulsars. Aims: To study the Crab pulsar emission with the LST-1, improving and complementing the results from other telescopes. These observations can also be used to characterize the potential of the LST-1 to study other pulsars and detect new ones. Methods: We analyzed a total of $\sim$103 hours of gamma-ray observations of the Crab pulsar conducted with the LST-1 in the period from September 2020 to January 2023. The observations were carried out at zenith angles less than 50 degrees. A new analysis of the Fermi-LAT data was also performed, including $\sim$14 years of observations. Results: The Crab pulsar phaseogram, long-term light-curve, and phase-resolved spectra are reconstructed with the LST-1 from 20 GeV to 450 GeV for P1 and up to 700 GeV for P2. The pulsed emission is detected with a significance of 15.2$\sigma$. The two characteristic emission peaks of the Crab pulsar are clearly detected (>10$\sigma$), as well as the so-called bridge emission (5.7$\sigma$). We find that both peaks are well described by power laws, with spectral indices of $\sim$3.44 and $\sim$3.03 respectively. The joint analysis of Fermi-LAT and LST-1 data shows a good agreement between both instruments in the overlapping energy range. The detailed results obtained in the first observations of the Crab pulsar with LST-1 show the potential that CTAO will have to study this type of sources

A detailed study of the very-high-energy Crab pulsar emission with the LST-1

International audienceContext: There are currently three pulsars firmly detected by imaging atmospheric Cherenkov telescopes (IACTs), two of them reaching TeV energies, challenging models of very-high-energy (VHE) emission in pulsars. More precise observations are needed to better characterize pulsar emission at these energies. The LST-1 is the prototype of the Large-Sized Telescope, that will be part of the Cherenkov Telescope Array Observatory (CTAO). Its improved performance over previous IACTs makes it well suited for studying pulsars. Aims: To study the Crab pulsar emission with the LST-1, improving and complementing the results from other telescopes. These observations can also be used to characterize the potential of the LST-1 to study other pulsars and detect new ones. Methods: We analyzed a total of $\sim$103 hours of gamma-ray observations of the Crab pulsar conducted with the LST-1 in the period from September 2020 to January 2023. The observations were carried out at zenith angles less than 50 degrees. A new analysis of the Fermi-LAT data was also performed, including $\sim$14 years of observations. Results: The Crab pulsar phaseogram, long-term light-curve, and phase-resolved spectra are reconstructed with the LST-1 from 20 GeV to 450 GeV for P1 and up to 700 GeV for P2. The pulsed emission is detected with a significance of 15.2$\sigma$. The two characteristic emission peaks of the Crab pulsar are clearly detected (>10$\sigma$), as well as the so-called bridge emission (5.7$\sigma$). We find that both peaks are well described by power laws, with spectral indices of $\sim$3.44 and $\sim$3.03 respectively. The joint analysis of Fermi-LAT and LST-1 data shows a good agreement between both instruments in the overlapping energy range. The detailed results obtained in the first observations of the Crab pulsar with LST-1 show the potential that CTAO will have to study this type of sources

A detailed study of the very-high-energy Crab pulsar emission with the LST-1

International audienceContext: There are currently three pulsars firmly detected by imaging atmospheric Cherenkov telescopes (IACTs), two of them reaching TeV energies, challenging models of very-high-energy (VHE) emission in pulsars. More precise observations are needed to better characterize pulsar emission at these energies. The LST-1 is the prototype of the Large-Sized Telescope, that will be part of the Cherenkov Telescope Array Observatory (CTAO). Its improved performance over previous IACTs makes it well suited for studying pulsars. Aims: To study the Crab pulsar emission with the LST-1, improving and complementing the results from other telescopes. These observations can also be used to characterize the potential of the LST-1 to study other pulsars and detect new ones. Methods: We analyzed a total of $\sim$103 hours of gamma-ray observations of the Crab pulsar conducted with the LST-1 in the period from September 2020 to January 2023. The observations were carried out at zenith angles less than 50 degrees. A new analysis of the Fermi-LAT data was also performed, including $\sim$14 years of observations. Results: The Crab pulsar phaseogram, long-term light-curve, and phase-resolved spectra are reconstructed with the LST-1 from 20 GeV to 450 GeV for P1 and up to 700 GeV for P2. The pulsed emission is detected with a significance of 15.2$\sigma$. The two characteristic emission peaks of the Crab pulsar are clearly detected (>10$\sigma$), as well as the so-called bridge emission (5.7$\sigma$). We find that both peaks are well described by power laws, with spectral indices of $\sim$3.44 and $\sim$3.03 respectively. The joint analysis of Fermi-LAT and LST-1 data shows a good agreement between both instruments in the overlapping energy range. The detailed results obtained in the first observations of the Crab pulsar with LST-1 show the potential that CTAO will have to study this type of sources

A detailed study of the very-high-energy Crab pulsar emission with the LST-1

International audienceContext: There are currently three pulsars firmly detected by imaging atmospheric Cherenkov telescopes (IACTs), two of them reaching TeV energies, challenging models of very-high-energy (VHE) emission in pulsars. More precise observations are needed to better characterize pulsar emission at these energies. The LST-1 is the prototype of the Large-Sized Telescope, that will be part of the Cherenkov Telescope Array Observatory (CTAO). Its improved performance over previous IACTs makes it well suited for studying pulsars. Aims: To study the Crab pulsar emission with the LST-1, improving and complementing the results from other telescopes. These observations can also be used to characterize the potential of the LST-1 to study other pulsars and detect new ones. Methods: We analyzed a total of $\sim$103 hours of gamma-ray observations of the Crab pulsar conducted with the LST-1 in the period from September 2020 to January 2023. The observations were carried out at zenith angles less than 50 degrees. A new analysis of the Fermi-LAT data was also performed, including $\sim$14 years of observations. Results: The Crab pulsar phaseogram, long-term light-curve, and phase-resolved spectra are reconstructed with the LST-1 from 20 GeV to 450 GeV for P1 and up to 700 GeV for P2. The pulsed emission is detected with a significance of 15.2$\sigma$. The two characteristic emission peaks of the Crab pulsar are clearly detected (>10$\sigma$), as well as the so-called bridge emission (5.7$\sigma$). We find that both peaks are well described by power laws, with spectral indices of $\sim$3.44 and $\sim$3.03 respectively. The joint analysis of Fermi-LAT and LST-1 data shows a good agreement between both instruments in the overlapping energy range. The detailed results obtained in the first observations of the Crab pulsar with LST-1 show the potential that CTAO will have to study this type of sources