Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer.

Human (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on Vδ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating Vδ2pos T cells purified from liver metastases (CLM) of patients affected by colorectal cancer (CRC) compared to those of sex- and age-matched healthy donors. The peripheral blood of CLM patients underwent CHT is characterized by decreased amounts of Vδ2pos T cells showing a relative increase of terminally-differentiated CD27neg/CD45RApos (TEMRA) cells. The enrichment of this latter subset is associated with an increased expression of the senescent marker CD57. The acquisition of CD57 on TEMRA Vδ2pos T cells is also coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. These features resemble the acquisition of an immune-senescent profile by Vδ2pos T cells from CLM patients that received CHT, a phenomenon that is also associated with the loss of the co-stimulatory marker CD28 and with the induced expression of CD16. The group of CLM patients underwent CHT and older than 60 years old showed higher frequencies of CD57pos and TEMRA Vδ2pos T cells. Similar results were found for tumor infiltrating Vδ2pos T cell subset purified from CLM specimens of patients treated with CHT. The toxicity of CHT regimens also affects the homeostasis of Vδ2pos T cells by inducing higher frequencies of circulating CD57pos TEMRA subset in CLM underwent CHT and younger than 60 years old. Taken together, our data demonstrate that the enrichment of senescent Vδ2pos T cells in CLM patients is not only induced by patients' aging but also by the toxicity of CHT that further accelerates the accumulation of CD57pos TEMRA cells highly dysfunctional in their anti-tumor activities. These results are important to both predict the clinical outcome of CLM and to optimize those protocols of cell cancer immunotherapy employing unconventional Vδ2pos T cells

Radiosondaggi atmosferici nell’area etnea

RADIOSONDAGGI ATMOSFERICI NELL’AREA ETNE

Monitoring and forecasting Etna volcanic plumes

In this paper we describe the results of a project ongoing at the Istituto Nazionale di Geofisica e Vulcanologia (INGV). The objective is to develop and implement a system for monitoring and forecasting volcanic plumes of Etna. Monitoring is based at present by multispectral infrared measurements from the Spin Enhanced Visible and Infrared Imager on board the Meteosat Second Generation geosynchronous satellite, visual and thermal cameras, and three radar disdrometers able to detect ash dispersal and fallout. Forecasting is performed by using automatic procedures for: i) downloading weather forecast data from meteorological mesoscale models; ii) running models of tephra dispersal, iii) plotting hazard maps of volcanic ash dispersal and deposition for certain scenarios and, iv) publishing the results on a web-site dedicated to the Italian Civil Protection. Simulations are based on eruptive scenarios obtained by analysing field data collected after the end of recent Etna eruptions. Forecasting is, hence, supported by plume observations carried out by the monitoring system. The system was tested on some explosive events occurred during 2006 and 2007 successfully. The potentiality use of monitoring and forecasting Etna volcanic plumes, in a way to prevent threats to aviation from volcanic ash, is finally discussed

A Statistical Approach to Evaluate the Tephra Deposit and Ash Concentration from Puff Model Forecasts

In this paper we present a new statistical approach able to provide tephra deposit load and ash concentration using PUFF, a lagrangian model widely used to forecast volcanic ash dispersal during volcanic crisis. We perform a parametric study in order to analyze the influence of each input parameter on model outputs. For this test, we simulate two eruptive scenarios like to the 2001 (Scenario 1) and 1998 (Scenario 2) Etna eruptions using high resolution weather data and a domain of 170 x 170 km. Results show that for both scenarios, we are able to calculate the tephra deposit load and ash concentration but the use of millions of particles is required. Specifically, up to 33 and 220 millions of particles were necessary to accurately predict the tephra deposit and ash concentration in air, respectively. This is approximately two orders of magnitude larger than values typically considered running PUFF. The parametric study shows that the horizontal diffusion coefficient, the time step of the simulations, the topography and the standard deviation of the particle distribution greatly affect the model outputs. We also validate the model by best fit procedures. Results show a good comparison between field data of the 2001 Etna eruption and PUFF simulations, being inside 5 and 1/5 times the observed data, comparable with results of Eulerian models. This work will allow to reliably outlining the areas of contaminated airspace using PUFF or any other lagrangian model in order to define the No Fly Zone and ensure the safety to aviation operations as required after the Eyjafjallajökull eruption

Eruption column height estimation of the 2011-2013 Etna lava fountains

In this paper, we use calibrated images collected by the video-surveillance system of the Istituto Nazionale di Geofisica e Vulcanologia, Osservatorio Etneo, to retrieve the height of the eruption column during the recent Etna explosive activity. The analysis is carried out on nineteen lava fountains from the New South East Crater dataset. The novel procedure described in this work is achieved in three main steps: at first we calibrated the camera, then we selected the images which recorded the maximum phase of the eruptive activity, and finally we applied an appropriate correction to account for the plume projection on the camera line of sight due to the wind. The results show that the column altitudes range between 6 and 9 km (upper limit of the camera system). The comparison with the plume height values estimated from the analysis of several SEVIRI and MODIS satellite images, show a good agreement. Finally, for nine events we also evaluated the thickness of the volcanic plumes in the umbrella region which ranges between 2 and 3 km

Eruption column height estimation of the 2011-2013 Etna lava fountains

In this paper, we use calibrated images collected by the video-surveillance system of the Istituto Nazionale di Geofisica e Vulcanologia, Osservatorio Etneo, to retrieve the height of the eruption column during the recent Etna explosive activity. The analysis is carried out on nineteen lava fountains from the New South East Crater dataset. The novel procedure described in this work is achieved in three main steps: at first we calibrated the camera, then we selected the images which recorded the maximum phase of the eruptive activity, and finally we applied an appropriate correction to account for the plume projection on the camera line of sight due to the wind. The results show that the column altitudes range between 6 and 9 km (upper limit of the camera system). The comparison with the plume height values estimated from the analysis of several SEVIRI and MODIS satellite images, show a good agreement. Finally, for nine events we also evaluated the thickness of the volcanic plumes in the umbrella region which ranges between 2 and 3 km

Beam Dynamics Studies of Parallel-Bar Deflecting Cavities

We have performed three-dimensional simulations of beam dynamics for parallel-bar transverse electromagnetic mode (TEM) type RF separators: normal- and superconducting. The compact size of these cavities as compared to conventional TM110 type structures is more attractive particularly at low frequency. Highly concentrated electromagnetic fields between the parallel bars provide strong electrical stability to the beam for any mechanical disturbance. An array of eight 2-cell normal conducting cavities or a one- or two-cell superconducting structure are enough to produce the required vertical displacement at the Lambertson magnet. Both the normal and superconducting structures show very small emittance dilution due to the vertical kick of the beam

Improvement of ash plume monitoring, modeling and hazard assessment in the MED-SUV project

Volcanic ash clouds produced by explosive eruptions represent a strong problem for civil aviation, road transportation and other human activities. Since Etna volcano produced in the last 35 years more the 200 explosive eruptions of small and medium size. The INGV, liable for its volcano monitoring, developed since 2006 a specific system for forecasting and monitoring Etna’s volcanic ash plumes in collaboration with several national and international institutions. Between 12 January 2011 and 31 December 2013 Etna produced forty-six basaltic lava fountains. Every paroxysm produced an eruption column ranging from a few up to eleven kilometers of height above sea level. The ash cloud contaminated the controlled airspace (CTR) of Catania and Reggio Calabria airports and caused tephra fallout on eastern Sicily sometime disrupting the operations of these airports. In order to give prompt and detailed warnings to the Aviation and Civil Protection authorities, ash plumes monitoring at Osservatorio Etneo, the INGV department in Catania, is carried out using multispectral (from visible to infrared) satellite and ground-based video-surveillance images; seismic and infrasound signals processed in real-time, a Doppler RADAR (Voldorad IIB) able to detect the eruption column in all weather conditions and a LIDAR (AMPLE) for retrieving backscattering and depolarization values of the ash clouds. Forecasting is performed running tephra dispersal models using weather forecast data, and then plotting results on maps published on a dedicated website. 24/7 Control Room operators were able to timely nform Aviation and Civil Protection operators for an effective aviation safety management. A variety of multidisciplinary activities are planned in the MED-SUV project with reference to volcanic ash observations and studies. These include: 1) physical and analogue laboratory experiments on ash dispersal and aggregation; 2) integration of satellite data (e.g. METEOSAT, MODIS) and ground- based measurements (e.g., RADAR, LIDAR) of Etna’s volcanic plumes to quantify mass eruption rate, grain-size distribution at source, and ash cloud concentration; 3) improvement of tools and automatic procedures for the short-term forecasting of volcanic ash dispersal by adopting a multi-model and multi-scenario approach; 4) development of short-term forecasting tools able to use direct measurements of the plume and ash cloud in almost real time (now-casting); 5) development of long-term probabilistic ash fallout maps at the supersite volcanoes.PublishedVienna, Austria4V. Vulcani e ambienteope

Science Requirements and Conceptual Design for a Polarized Medium Energy Electron-Ion Collider at Jefferson Lab

This report presents a brief summary of the science opportunities and program of a polarized medium energy electron-ion collider at Jefferson Lab and a comprehensive description of the conceptual design of such a collider based on the CEBAF electron accelerator facility.Comment: 160 pages, ~93 figures This work was supported by the U.S. Department of Energy, Office of Nuclear Physics, under Contract No. DE-AC05-06OR23177, DE-AC02-06CH11357, DE-AC05-060R23177, and DESC0005823. The U.S. Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce this manuscript for U.S. Government purpose

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values. We found that the correlation of [Formula: see text] with the reference standard ([Formula: see text]/[Formula: see text] ratio) improves substantially when excluding [Formula: see text] and refer to this measure as [Formula: see text]. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that [Formula: see text] is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using [Formula: see text]. We demonstrate that [Formula: see text] is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power