LIME -- a gas TPC prototype for directional Dark Matter search for the CYGNO experiment

The CYGNO experiment aims at the development of a large gaseous TPC with GEM-based amplification and an optical readout by means of PMTs and scientific CMOS cameras for 3D tracking down to O(keV) energies, for the directional detection of rare events such as low mass Dark Matter and solar neutrino interactions. The largest prototype built so far towards the realisation of the CYGNO experiment demonstrator is the 50 L active volume LIME, with 4 PMTs and a single sCMOS imaging a 33$\times$33 cm\textsuperscript{2} area for 50 cm drift, that has been installed in underground Laboratori Nazionali del Gran Sasso in February 2022. We will illustrate LIME performances as evaluated overground in Laboratori Nazionali di Frascati by means of radioactive X-ray sources, and in particular the detector stability, energy response and energy resolution. We will discuss the MC simulation developed to reproduce the detector response and show the comparison with actual data. We will furthermore examine the background simulation worked out for LIME underground data taking and illustrate the foreseen expected measurement and results in terms of natural and materials intrinsic radioactivity characterisation and measurement of the LNGS underground natural neutron flux. The results that will be obtained by underground LIME installation will be paramount in the optimisation of the CYGNO demonstrator, since this is foreseen to be composed by multiple modules with the same LIME dimensions and characteristics

Identification of clusters of asthma control: A preliminary analysis of the inspirers studies

This work was funded by ERDF (European Regional Development Fund) through the operations: POCI- -01-0145-FEDER-029130 (“mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases - generalisation and evaluation of gamification, peer support and advanced image processing technologies”) co-funded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).© 2020, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All rights reserved. Aims: To identify distinct asthma control clusters based on Control of Allergic Rhinitis and Asthma Test (CARAT) and to compare patients’ characteristics among these clusters. Methods: Adults and adolescents (≥13 years) with persistent asthma were recruited at 29 Portuguese hospital outpatient clinics, in the context of two observational studies of the INSPIRERS project. Demographic and clinical characteristics, adherence to inhaled medication, beliefs about inhaled medication, anxiety and depression, quality of life, and asthma control (CARAT, >24 good control) were collected. Hierarchical cluster analysis was performed using CARAT total score (CARAT-T). Results: 410 patients (68% adults), with a median (percentile 25–percentile 75) age of 28 (16-46) years, were analysed. Three clusters were identified [mean CARAT-T (min-max)]: cluster 1 [27(24-30)], cluster 2 [19(14-23)] and cluster 3 [10(2-13)]. Patients in cluster 1 (34%) were characterised by better asthma control, better quality of life, higher inhaler adherence and use of a single inhaler. Patients in clusters 2 (50%) and 3 (16%) had uncontrolled asthma, lower inhaler adherence, more symptoms of anxiety and depression and more than half had at least one exacerbation in the previous year. Further-more, patients in cluster 3 were predominantly female, had more unscheduled medical visits and more anxiety symp-toms, perceived a higher necessity of their prescribed inhalers but also higher levels of concern about taking these inhalers. There were no differences in age, body mass index, lung function, smoking status, hospital admissions or specialist physician follow-up time among the three clusters. Conclusion: An unsupervised method based on CARAT--T, identified 3 clusters of patients with distinct, clinically meaningful characteristics. The cluster with better asthma control had a cut-off similar to the established in the validation study of CARAT and an additional cut-off seems to distinguish more severe disease. Further research is necessary to validate the asthma control clusters identified.publishersversionpublishe

Technical Design Report - TDR CYGNO-04/INITIUM

The aim of this Technical Design Report is to illustrate the technological choices foreseen to be implemented in the construction of the CYGNO-04 demonstrator, motivate them against the experiment physics goals of CYGNO-30 and demonstrate the financial sustainability of the project. CYGNO-04 represents PHASE 1 of the long term CYGNO roadmap, towards the development of large high precision tracking gaseous Time Projection Chamber (TPC) for directional Dark Matter searches and solar neutrino spectroscopy. The CYGNO project1 peculiarities reside in the optical readout of the light produced during the amplification of the primary ionization electrons in a stack of triple Gas Electron Multipliers (GEMs), thanks to the nice scintillation properties of the chosen He:CF4 gas mixture. To this aim, CYGNO is exploiting the fast progress in commercial scientific Active Pixel Sensors (APS) development for highly performing sCMOS cameras, whose high granularity and sensitivity allow to significantly boost tracking, improve particle identification and lower the energy threshold. The X-Y track project obtained from the reconstruction of the sCMOS images is combined with a PMT measurement to obtain a full 3D track reconstruction. In addition, several synergic R&Ds based on the CYGNO experimental approach are under development in the CYGNO collaboration (see Sec 2) to further enhance the light yield by means of electro luminescence after the amplification stage, to improve the tracking performances by exploiting negative ion drift operation within the INITIUM ERC Consolidator Grant, and to boost the sensitivity to O(GeV) Dark Matter masses by employing hydrogen rich target towards the development of PHASE 2 (see Sec. 1.2). While still under optimization and subject to possible significant improvements, the CYGNO experimental approach performances and capabilities demonstrated so far with prototypes allow to foresee the development of an O(30) m3 experiment by 2026 for a cost of O(10) MEUROs. A CYGNO-30 experiment would be able to give a significant contribution to the search and study of Dark Matter with masses below 10 GeV/c2 for both SI and SD coupling. In case of a Dark Matter observation claim by other experiments, the information provided by a directional detector such as CYGNO would be fundamental to positively confirm the galactic origin of the allegedly detected Dark Matter signal. CYGNO-30 could furthermore provide the first directional measurement of solar neutrinos from the pp chain, possibly extending to lower energies the Borexino measurement2. In order to reach this goal, the CYGNO project is proceeding through a staged approach. The PHASE 0 50 L detector (LIME, recently installed underground LNGS) will validate the full performances of the optical readout via APS commercial cameras and PMTs and the Montecarlo simulation of the expected backgrounds. The full CYGNO-04 demonstrator will be realized with all the technological and material choices foreseen for CYGNO-30, to demonstrate the scalability of the experimental approach and the potentialities of the large PHASE 2 detector to reach the expected physics goals. The first PHASE 1 design anticipated a 1 m3 active volume detector with two back-to-back TPCs with a central cathode and 500 mm drift length. Each 1 m2 readout area would have been composed by 9 + 9 readout modules having the LIME PHASE 0 dimensions and layout. Time (end of INITIUM project by March 2025) and current space availability at underground LNGS (only Hall F) forced the rescaling of the PHASE 1 active volume and design to a 0.4 m3, hence CYGNO-04. CYGNO-04 will keep the back-to-back double TPC layout with 500 mm drift length each, but with an 800 x 500 mm2 readout area covered by a 2 + 2 modules based on LIME design. The reduction of the detector volume has no impact on the technological objectives of PHASE 1, since the modular design with central cathode, detector materials and shieldings and auxiliary systems are independent of the total volume. The physics reach (which is a byproduct of PHASE 1 and NOT an explicit goal) will be only very partially reduced (less than a factor 2 overall) since a smaller detector volume implies also a reduced background from internal materials radioactivity. In addition, the cost reduction of CYGNO-04 of about 1⁄3 with respect to CYGNO-1 illustrated in the CDR effectively makes the overall project more financially sustainable (see CBS in the last section). In summary this document will explain: the physical motivation of the CYGNO project and the technical motivations of the downscale of the PHASE 1 to CYGNO-04, 400 liters of active volume, with respect to the demonstrator presented in the CDR; the results of R&D and the Montecarlo expectations for PHASE 0; the technical choices, procedures and the executive drawings of CYGNO-04 in the Hall F of the LNGS; safety evaluations and the interference/request to the LNGS services; Project management, WBS/WBC, WP, GANTT, ec

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The CYGNO Experiment

The search for a novel technology able to detect and reconstruct nuclear and electron recoil events with the energy of a few keV has become more and more important now that large regions of high-mass dark matter (DM) candidates have been excluded. Moreover, a detector sensitive to incoming particle direction will be crucial in the case of DM discovery to open the possibility of studying its properties. Gaseous time projection chambers (TPC) with optical readout are very promising detectors combining the detailed event information provided by the TPC technique with the high sensitivity and granularity of latest-generation scientific light sensors. The CYGNO experiment (a CYGNus module with Optical readout) aims to exploit the optical readout approach of multiple-GEM structures in large volume TPCs for the study of rare events as interactions of low-mass DM or solar neutrinos. The combined use of high-granularity sCMOS cameras and fast light sensors allows the reconstruction of the 3D direction of the tracks, offering good energy resolution and very high sensitivity in the few keV energy range, together with a very good particle identification useful for distinguishing nuclear recoils from electronic recoils. This experiment is part of the CYGNUS proto-collaboration, which aims at constructing a network of underground observatories for directional DM search. A one cubic meter demonstrator is expected to be built in 2022/23 aiming at a larger scale apparatus (30 m$^3$--100 m$^3$) at a later stage

Medição da mobilidade de iões negativos em gases de interesse para NITPCs

Trabalho de Projeto do Mestrado Integrado em Engenharia Física apresentado à Faculdade de Ciências e TecnologiaDetetores gasosos são usados em diversas áreas desde física de altas energias até buscas de eventos raros devido às suas grandes capacidades de identificação e tracking de partículas. Para melhorar estas capacidades, vários esforços têm vindo a ser realizados para melhorar ou desenvolver novos sistemas de amplificação e leitura sensíveis à posição. Em detetores gasosos que recorrem à deriva de eletrões para fazer track e medir a energia de partículas ionizantes, uma das maiores restrições é a difusão dos eletrões. Isto é especialmente relevante em detetores gasosos de grande volume. Para ultrapassar esta limitação, as Câmaras de Projeção Temporal de Iões Negativos (em inglês, Negative Ion Time Projection Chambers, NITPCs) foram desenvolvidas. Em vez de fazerem uso de eletrões, estes detetores usam iões negativos como portadores de carga, explorando a sua menor difusão, comparando com a dos eletrões. Com a recente descoberta de portadores de carga minoritários, é esperado que nestas câmaras seja possível determinar a posição absoluta do evento ionizante ao longo da direção de deriva, analisando as diferenças no tempo de deriva das várias espécies de iões minoritários criados a partir do mesmo gás eletronegativo. Para apoiar o desenvolvimento de NITPCs, uma nova câmara capaz de medir a mobilidade de iões positivos e negativos foi desenvolvida no LIP: a Câmara de Deriva de Iões de Dupla-Polaridade (em inglês, Dual-Polarity Ion Drift Chamber, DP-IDC). A DP-IDC é uma câmara de deriva de iões que inclui um multiplicador de eletrões gasoso (em inglês, Gas Electron Multiplier, GEM) com um depósito de CsI (Iodeto de Césio) no centro da câmara, duas grelhas duplas em cada extremidade e um conjunto de anéis de campo elétrico que criam um campo elétrico uniforme em toda a região de deriva. O GEM, neste sistema, tem um ganho muito baixo pois o seu objetivo principal é apenas criar iões enquanto os eletrões atravessam os seus orifícios. Com uma lâmpada UV no topo, é possível produzir fotoeletrões junto do GEM quando o fotocátodo de CsI (depositado no elétrodo superior do GEM) sofre o impacto dos fotões UV, criando também o ponto temporal inicial da medição (trigger). Sabendo a distância de deriva e depois de analisar os espetros dos tempos de chegada, é possível determinar a velocidade dos iões e calcular a sua mobilidade reduzida para diferentes gases, pressões, temperaturas, entre outros parâmetros. O primeiro protótipo da DP-IDC mostrou algumas limitações importantes. Por esse motivo, para melhorar este detetor, várias modificações foram implementadas, nomeadamente o desenvolvimento de um novo componente central capaz de suportar o GEM e assegurar a uniformidade do campo elétrico em toda a região de deriva. Após esta modificação, a câmara foi testada através de vários estudos preliminares. Estes permitiram uma melhor compreensão da influência de diferentes variáveis no espetro de deriva. Estes estudos focaram-se na influência da pressão e na presença de aglomerados (clusters) de iões e impurezas do gás nas mobilidades obtidas. Para além destes tópicos, a influência do campo elétrico nos orifícios do GEM também foi cuidadosamente estudada. Provou-se que a diferença de potencial aplicada no GEM afeta fortemente o tipo de iões criados dentro da câmara. Outros estudos focados em, por exemplo, o sinal induzido pela lâmpada foram também realizados para que fosse possível compreender melhor o processo de formação de sinal com este sistema. Nesta tese, são apresentados os resultados obtidos com SF6 puro e misturas baseadas em SF6. Escolheu-se SF6 pois este é assumido como sendo um forte candidato para as próximas gerações de NITPCs. A preferência por SF6 vem do facto de que é esperada a presença de duas espécies distintas de iões (SF6- e SF5-) o que permite a determinação da posição z absoluta de um evento ionizante em NITPCs. Nesta dissertação, a mobilidade de iões de SF6 (SF6-, SF5- e, possivelmente, SF4-) foi medida para diferentes pressões (até 30 Torr) e para diferentes campo elétricos reduzidos (até 40 Td). As mobilidades obtidas mostraram-se em acordo com a informação publicada. Estudos similares com SF6-CF4 e SF6-N2 também foram realizados onde as mobilidades obtidas também se encontraram dentro do esperado, comparando tanto com a literatura disponível como com os valores teóricos obtidos com a lei de Blanc. A identificação de diferentes espécies de iões criados e o rácio entre eles, para cada conjunto de parâmetros, mostrou-se possível de realizar com a DP-IDC, usando SF6. Isto trata-se de uma característica fundamental para o desenvolvimento de detetores de deriva de iões negativos (tais como as NITPCs). Além disso, a verificação da boa performance da DP-IDC vai permitir que estudos ligados à deriva de iões negativos em diferentes misturas gasosas e diferentes condições de pressão e campo elétrico reduzido possam ser realizados, tão bem como estudos focados na difusão de iões.Gaseous detectors are widely used in many fields ranging from high energy physics to rare-event searches due to their high tracking and particle identification capabilities. To further improve these features, several efforts are being carried in order to improve or develop new position-sensitive electron amplification and readout systems. In gaseous detectors that resort to electron drift to track and measure the energy of ionizing particles, one of the biggest constraints is the electron diffusion. This is especially relevant in large volume gas radiation detectors. To surpass such limitation, Negative Ion Time Projection Chambers (NITPCs) were developed. Instead of making use of electrons, these detectors explore negative ions as charge carriers, exploiting their much smaller diffusion, when compared to electrons. With the recent discovery of minority charge carriers, these chambers are also expected to be able to determine the absolute position of the ionizing event along the drift direction by analysing the drift time differences between the several minority ion species created from the same electronegative gas. To support the development of NITPCs, a new chamber capable of measuring the ion mobility of both positive and negative ions was developed at LIP: the Dual-Polarity Ion Drift Chamber (DP-IDC). The DP-IDC is an ion drift chamber that includes a Gas Electron Multiplier (GEM) with a CsI deposit in the middle of the chamber, two double grids in each endcap and a series of electric field rings that create a uniform electric field throughout the drift region. The GEM, in this setup, has a very low gain as its main objective is to create ions while the electrons drift through its holes. With a UV-lamp on the top, it is possible to produce photoelectrons near the GEM when the CsI photocathode (deposited on the top electrode of the GEM) is hit by the UV photons, while also providing a trigger for the measurement. Knowing the drift distance and after analysing the time of arrival spectra, it is possible to determine the ions’ velocity and to calculate their reduced mobility for different gases, pressures, temperatures, amongst other parameters. The first prototype of the DP-IDC has shown several important limitations. Thus, to improve this detector, several modifications were implemented, namely the development of a new central component capable of both supporting/holding the GEM and ensuring a uniform electric field through the whole drift region. After this modification, the chamber was tested with several preliminary studies. These allowed to better understand the influence of different variables in the drift spectra. Such studies were focused on the influence of the pressure and the presence of ion clusters and gas impurities on the mobilities obtained. Together with these, the influence of the electric field in the GEM's holes was also carefully studied. The voltage applied on the GEM proved to strongly affect the type of ions created within the chamber. Other studies concerning, for instance, the lamp induced signal were also carried to better understand the signal formation with this experimental setup. In this work, the results obtained with pure SF6 and SF6 based mixtures are presented. SF6 was chosen as it is assumed to be a strong candidate for the next generation of NITPCs. The preference for SF6 relies on the fact that two distinct ion species are expected to be present (SF6- and SF5-) allowing therefore for the determination of the absolute z position of an ionization event in NITPCs. The mobility of SF6 ions (SF6-, SF5- and, possibly, SF4-) have been measured in this work for different pressures (up to 30 Torr) and different reduced electric fields (up to 40 Td). The mobilities obtained have shown to be in accordance with most of the published data. Similar studies with SF6-CF4 and SF6-N2 were also carried and the mobilities obtained are also within the expected, both comparing with the literature and theoretical values retrieved from Blanc's law. The identification of the different ion species created for each set of parameters as well as the ratio among themselves has proven to be attainable with the DP-IDC using SF6. This is a key feature for the development of negative ion drift detectors (such as NITPCs). Moreover, by verifying the initial great performance of the DP-IDC, further studies can be carried regarding negative ion drift in different gas mixtures and different conditions of pressure and reduced electric field as well as studies concerning ion diffusion and the presence of ion clusters

LIME. A gas TPC prototype for directional Dark Matter search for the CYGNO experiment

The CYGNO experiment aims at the development of a large gaseous TPC with GEM-based amplification and an optical readout by means of PMTs and scientific CMOS cameras for 3D tracking down to O(keV) energies, for the directional detection of rare events such as low mass Dark Matter and solar neutrino interactions. The largest prototype built so far towards the realisation of the CYGNO experiment demonstrator is the 50 L active volume LIME, with 4 PMTs and a single sCMOS imaging a 33×33 cm2 area for 50 cm drift, that has been installed in underground Laboratori Nazionali del Gran Sasso in February 2022. We will illustrate LIME performances as evaluated overground in Laboratori Nazionali di Frascati by means of radioactive X-ray sources, and in particular the detector stability, energy response and energy resolution. We will discuss the MC simulation developed to reproduce the detector response and show the comparison with actual data. We will furthermore examine the background simulation worked out for LIME underground data taking and illustrate the foreseen expected measurement and results in terms of natural and materials intrinsic radioactivity characterisation and measurement of the LNGS underground natural neutron flux. The results that will be obtained by underground LIME installation will be paramount in the optimisation of the CYGNO demonstrator, since this is foreseen to be composed by multiple modules with the same LIME dimensions and characteristic

The CYGNO experiment, a directional detector for direct Dark Matter searches

The CYGNO project aims at the development of a high precision optical readout gaseous Tima Projection Chamber (TPC) for directional dark matter (DM) searches, to be hosted at Laboratori Nazionali del Gran Sasso (LNGS). CYGNO employs a He:CF gas mixture at atmospheric pressure with a Gas Electron Multiplier (GEM) based amplification structure coupled to an optical readout comprised of sCMOS cameras and photomultiplier tubes (PMTs). This experimental setup allows to achieve 3D tracking and background rejection down to O(1) keV energy, to boost sensitivity to low WIMP masses. The characteristics of the optical readout approach in terms of the light yield will be illustrated along with the particle identification properties. The project timeline foresees, in the next 2–3 years, the realisation and installation of a 0.4 m3 TPC in the underground laboratories at LNGS to act as a demonstrator. Finally, the studies of the expected DM sensitivities of the CYGNO demonstrator will be presented