A 50 l CYGNO prototype overground characterization

The nature of dark matter is still unknown and an experimental program to look for dark matter particles in our Galaxy should extend its sensitivity to light particles in the GeV mass range and exploit the directional information of the DM particle motion (Vahsen et al. in CYGNUS: feasibility of a nuclear recoil observatory with directional sensitivity to dark matter and neutrinos, arXiv:2008.12587, 2020). The CYGNO project is studying a gaseous time projection chamber operated at atmospheric pressure with a Gas Electron Multiplier (Sauli in Nucl Instrum Meth A 386:531, https://doi.org/10.1016/S0168-9002(96)01172-2, 1997) amplification and with an optical readout as a promising technology for light dark matter and directional searches. In this paper we describe the operation of a 50 l prototype named LIME (Long Imaging ModulE) in an overground location at Laboratori Nazionali di Frascati (LNF) of INFN. This prototype employs the technology under study for the 1 cubic meter CYGNO demonstrator to be installed at the Laboratori Nazionali del Gran Sasso (LNGS) (Amaro et al. in Instruments 2022, 6(1), https://www.mdpi.com/2410-390X/6/1/6, 2022). We report the characterization of LIME with photon sources in the energy range from few keV to several tens of keV to understand the performance of the energy reconstruction of the emitted electron. We achieved a low energy threshold of few keV and an energy resolution over the whole energy range of 10–20%, while operating the detector for several weeks continuously with very high operational efficiency. The energy spectrum of the reconstructed electrons is then reported and will be the basis to identify radio-contaminants of the LIME materials to be removed for future CYGNO detectors

Directional iDBSCAN to detect cosmic-ray tracks for the CYGNO experiment

The CYGNO experiment aims to study rare events related to the search for low-mass dark matter and solar neutrino events. One of the main components of background comes from cosmic rays that generate long tracks in the detector's images. The interaction of such particles with the gas releases a variable energy profile along its trajectory to form tracks with multiple cores that can be easily reconstructed erroneously by being split into more than one cluster. Thus, this work offers a newly adapted version of the well-known density-based spatial clustering of applications with noise (DBSCAN) algorithm, called iDDBSCAN, which exploits the directional characteristics of the clusters found by the DBSCAN to improve its clustering efficiency when dealing with multi-core tracks. This paper provides a detailed explanation of this algorithm, covering its parameter validation and evaluating its influence when integrated into the experiment's event selection routine. To generate background events, data acquisition was performed with the detector installed in an overground laboratory, leaving it exposed to natural radiation. To produce signals in the energy range of interest for the experiment, a 55Fe radioactive source was used. The achieved results showed that the iDDBSCAN algorithm is capable of improving the background rejection of the experiment, through a more accurate reconstruction of the tracks produced by natural radiation such as cosmic rays, without deteriorating its signal detection efficiency and energy estimation

50 litres TPC with sCMOS-based optical readout for the CYGNO project

The CYGNO project aims at realising a one cubic meter gaseous Time Projection Chamber (TPC) equipped with Scientific CMOS (sCMOS) commercial cameras to optically readout Gas Electron Multiplier (GEM) to be operated at the underground of Gran Sasso National Laboratory (LNGS). The purpose of the project is to study the technology needed for a large size gaseous TPC (30–100 m ) operated at atmospheric pressure for the directional search of low mass O(GeV) dark matter and low energy (eg solar) neutrinos astronomy. The roadmap of the project foresees the underground operation of a 50 litres TPC prototype, called LIME, the largest TPC realised with this technology, fully equipped with copper and water shielding. LIME is equivalent to about a 1/20 of the CYGNO demonstrator and aims to validate: The construction materials, the Monte Carlo simulations, the data reconstruction and the particle identification performances at low energy threshold. LIME is under installation at the LNGS and it is supposed to start data taking at the beginning of 2022. The detector description and installation will be presented, as well as the overground performance and limitations that require underground characterisation

Noise assessment of CMOS active pixel sensors for the CYGNO Experiment

Active Pixel sensors play a crucial role in enabling successful low-light scientific experiments due to their inherent advantages and capabilities. Such devices not only offer high spatial resolution but also feature individual pixels with integrated amplifiers, allowing for direct signal amplification at the pixel level. This results in reduced readout noise and improved signal-to-noise ratio (SNR), which are particularly vital when dealing with limited photon counts in low-light environments. This holds particularly true for scientific CMOS (sCMOS) sensors, acknowledged as an advanced evolution of Active Pixel sensors. However, despite their advantages, such sensors can still exhibit limitations such as higher cost and presence of noise artifacts that should be closely investigated. In particular, CYGNO project fits in a global effort aimed at direct detection of Dark Matter particles. CYGNO collaboration intends to build a detector based on a Time Projection Chamber making use of Gas Electron Multipliers for the amplification of ionization electrons. The GEM multiplication process produces photons that can be readout by a high-resolution sCMOS sensor. Such detection system is being designed to have enough sensitivity to detect low-energy particles and to measure released energy with enough granularity so to reconstruct direction and energy profile along their trajectories. The image sensor has an important role in the detector performance, having a direct impact on the SNR of the experiment. This work proposes a study on the performance of three different sCMOS sensors with respect to their sensitivity to low-energy particles and their intrinsic noise, which are of the utmost importance for various scientific experiments

The CYGNO experiment: a directional Dark Matter detector with optical readout

We are going to discuss the R&D and the prospects for the CYGNO project, towards the development of an innovative, high precision 3D tracking Time Projection Chamber with optical readout using He:CF4 gas at 1 bar. CYGNO uses a stack of triple thin GEMs for charge multiplication, this induces scintillation in CF4 gas, which is readout by PMTs and sCMOS cameras. High granularity and low readout noise of sCMOS along with high sampling of PMT allows CYGNO to have 3D tracking with head tail capability and particle identification down to O(keV) energy for directional Dark Matter searches and solar neutrino spectroscopy. We will present the most recent R&D results from the CYGNO project, and in particular the overground commissioning of the largest prototype developed so far, LIME with a 33×33 cm2 readout plane and 50 cm of drift length, for a total of 50 litres active volume. We will illustrate the LIME response characterisation between 3.7 keV and 44 keV by means of multiple X-ray sources, and the data Monte-Carlo comparison of simulated sCMOS images in this energy range. Furthermore, we will present current LIME installation, operation and data taking at underground Laboratori Nazionali del Gran Sasso (LNGS), serving as demonstrator for the development of a 0.4 m3 CYGNO detector. We will conclude by mentioning the technical choices and the prospects of the 0.4 m3 detector, as laid out in the Technical Design Report (TDR) recently produced by our collaboration

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial.

BackgroundTreatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.MethodsendTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.DiscussionThe lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.Trial registrationClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial

Abstract Background Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients. Methods endTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations. Discussion This internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen. Trial registration ClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023