Search

We present the model we developed to reconstruct the CUORE radioactive background based on the analysis of an experimental exposure of 1038.4 kg yr. The data reconstruction relies on a simultaneous Bayesian fit applied to energy spectra over a broad energy range. The high granularity of the CUORE detector, together with the large exposure and extended stable operations, allow for an in-depth exploration of both spatial and time dependence of backgrounds. We achieve high sensitivity to both bulk and surface activities of the materials of the setup, detecting levels as low as 10 nBq kg-1 and 0.1 nBq cm-2, respectively. We compare the contamination levels we extract from the background model with prior radio-assay data, which informs future background risk mitigation strategies. The results of this background model play a crucial role in constructing the background budget for the CUPID experiment as it will exploit the same CUORE infrastructure.

The current experiments searching for neutrinoless double-β (0νββ) decay also collect large statistics of Standard Model allowed two-neutrino double-β (2νββ) decay events. These can be used to search for Beyond Standard Model (BSM) physics via 2νββ decay spectral distortions. 100Mo has a natural advantage due to its relatively short half-life, allowing higher 2νββ decay statistics at equal exposures compared to the other isotopes. We demonstrate the potential of the dual read-out bolometric technique exploiting a 100Mo exposure of 1.47 kg × years, acquired in the CUPID-Mo experiment at the Modane underground laboratory (France). We set limits on 0νββ decays with the emission of one or more Majorons, on 2νββ decay with Lorentz violation, and 2νββ decay with a sterile neutrino emission. In this analysis, we investigate the systematic uncertainty induced by modeling the 2νββ decay spectral shape parameterized through an improved model, an effect never considered before. This work motivates searches for BSM processes in the upcoming CUPID experiment, which will collect the largest amount of 2νββ decay events among the next-generation experiments.

We study the effects of the first nontrivial hexaquark, $d^*$(2380), on theequation of state of dense neutron star matter and investigate the consequencesof its existence for neutron stars. The matter in the core regions of neutronstars is described using density-dependent relativistic mean-field theory. Ourresults show that within the parameter spaces examined in our paper, (i) thecritical density at which the $d^*$ condensate emerges lies between 4 and 5times the nuclear saturation density, (ii) $d^*$ hexaquarks are found to existonly in rather massive neutron stars, (iii) only relatively small fractions ofthe matter in the core of a massive neutron star may contain hexaquarks.

Neutrinoless double beta decay (0νββ) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νββ) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νββ decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.07±0.02(stat)±0.11(syst)]×10^{18}  yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νββ decay rate in ^{100}Mo. In addition, we constrain higher-order corrections to the spectral shape, which provides complementary nuclear structure information. We report a novel measurement of the shape factor ξ_{3,1}=0.45±0.03(stat)±0.05(syst) based on a constraint on the ratio of higher-order terms from theory, which can be reliably calculated. This is compared to theoretical predictions for different nuclear models. We also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νββ decay.

Background Mortality prediction in critically ill patients with cardiogenic shock can guide triage and selection of potentially high-risk treatment options. Methods and Results We developed and externally validated a checklist risk score to predict in-hospital mortality among adults admitted to the cardiac intensive care unit with Society for Cardiovascular Angiography & Interventions Shock Stage C or greater cardiogenic shock using 2 real-world data sets and Risk-Calibrated Super-sparse Linear Integer Modeling (RiskSLIM). We compared this model to those developed using conventional penalized logistic regression and published cardiogenic shock and intensive care unit mortality prediction models. There were 8815 patients in our training cohort (in-hospital mortality 13.4%) and 2237 patients in our validation cohort (in-hospital mortality 22.8%), and there were 39 candidate predictor variables. The final risk score (termed BOS,MA2) included maximum blood urea nitrogen ≥25 mg/dL, minimum oxygen saturation

CUPID is a next-generation bolometric experiment aiming at searching for neutrinoless double-beta decay with ∼250 kg of isotopic mass of 100Mo. It will operate at ∼10 mK in a cryostat currently hosting a similar-scale bolometric array for the CUORE experiment at the Gran Sasso National Laboratory (Italy). CUPID will be based on large-volume scintillating bolometers consisting of 100Mo-enriched Li2MoO4 crystals, facing thin Ge-wafer-based bolometric light detectors. In the CUPID design, the detector structure is novel and needs to be validated. In particular, the CUORE cryostat presents a high level of mechanical vibrations due to the use of pulse tubes and the effect of vibrations on the detector performance must be investigated. In this paper we report the first test of the CUPID-design bolometric light detectors with NTD-Ge sensors in a dilution refrigerator equipped with a pulse tube in an above-ground lab. Light detectors are characterized in terms of sensitivity, energy resolution, pulse time constants, and noise power spectrum. Despite the challenging noisy environment due to pulse-tube-induced vibrations, we demonstrate that all the four tested light detectors comply with the CUPID goal in terms of intrinsic energy resolution of 100 eV RMS baseline noise. Indeed, we have measured 70-90 eV RMS for the four devices, which show an excellent reproducibility. We have also obtained high energy resolutions at the 356 keV line from a 133Ba source, as good as Ge semiconductor γ detectors in this energy range.

An array of twelve 0.28 kg lithium molybdate (LMO) low-temperature bolometers equipped with 16 bolometric Ge light detectors, aiming at optimization of detector structure for CROSS and CUPID double-beta decay experiments, was constructed and tested in a low-background pulse-tube-based cryostat at the Canfranc underground laboratory in Spain. Performance of the scintillating bolometers was studied depending on the size of phonon NTD-Ge sensors glued to both LMO and Ge absorbers, shape of the Ge light detectors (circular vs. square, from two suppliers), in different light collection conditions (with and without reflector, with aluminum coated LMO crystal surface). The scintillating bolometer array was operated over 8 months in the low-background conditions that allowed to probe a very low, μBq/kg, level of the LMO crystals radioactive contamination by 228Th and 226Ra.

CUPID is a next-generation tonne-scale bolometric neutrinoless double beta decay experiment that will probe the Majorana nature of neutrinos and discover lepton number violation in case of observation of this singular process. CUPID will be built on experience, expertise and lessons learned in CUORE and will be installed in the current CUORE infra-structure in the Gran Sasso underground laboratory. The CUPID detector technology, successfully tested in the CUPID-Mo experiment, is based on scintillating bolometers of Li2MoO4 enriched in the isotope of interest 100Mo. In order to achieve its ambitious science goals, the CUPID collaboration aims to reduce the backgrounds in the region of interest by a factor 100 with respect to CUORE. This performance will be achieved by introducing the high efficient α/β discrimination demonstrated by the CUPID-0 and CUPID-Mo experiments, and using a high transition energy double beta decay nucleus such as 100Mo to minimize the impact of the gamma background. CUPID will consist of about 1500 hybrid heat-light detectors for a total isotope mass of 250 kg. The CUPID scientific reach is supported by a detailed and safe background model based on CUORE, CUPID-Mo and CUPID-0 results. The required performances have already been demonstrated and will be presented.

Next-generation experiments searching for rare events must satisfy increasingly stringent requirements on the bulk and surface radioactive contamination of their active and structural materials. The measurement of surface contamination is particularly challenging, as no existing technology is capable of separately measuring parts of the 232Th and 238U decay chains that are commonly found to be out of secular equilibrium. We will present the results obtained with a detector prototype consisting of 8 silicon wafers of 150 mm diameter instrumented as bolometers and operated in a low-background dilution refrigerator at the Gran Sasso Underground Laboratory of INFN, Italy. The prototype was characterized by a baseline energy resolution of few keV and a background

CUPID-Mo, located in the Laboratoire Souterrain de Modane (France), was a demonstrator for the next generation 0 νββ decay experiment, CUPID. It consisted of an array of 20 enriched Li 2100 MoO 4 bolometers and 20 Ge light detectors and has demonstrated that the technology of scintillating bolometers with particle identification capabilities is mature. Furthermore, CUPID-Mo can inform and validate the background prediction for CUPID. In this paper, we present a detailed model of the CUPID-Mo backgrounds. This model is able to describe well the features of the experimental data and enables studies of the 2 νββ decay and other processes with high precision. We also measure the radio-purity of the Li 2100 MoO 4 crystals which are found to be sufficient for the CUPID goals. Finally, we also obtain a background index in the region of interest of 3.7 -0.8+0.9 (stat) -0.7+1.5 (syst) ×10-3 counts/ Δ EFWHM/ mol iso/ year , the lowest in a bolometric 0 νββ decay experiment.

Digital health technologies have been in use for many years in a wide spectrum of healthcare scenarios. This narrative review outlines the current use and the future strategies and significance of digital health technologies in modern healthcare applications. It covers the current state of the scientific field (delineating major strengths, limitations, and applications) and envisions the future impact of relevant emerging key technologies. Furthermore, we attempt to provide recommendations for innovative approaches that would accelerate and benefit the research, translation and utilization of digital health technologies.

In this contribution we present the achievements of the CUORE experiment so far. It is the first tonne-scale bolometric detector and it is in stable data taking since 2018. We reached to collect about 1800 kg×yr of exposure of which more than 1 ton×year have been analysed. The CUORE detector is meant to search for the neutrinoless double β decay (0νββ) of the 130Te isotope. This is a beyond Standard Model process which could establish the nature of the neutrino to be Dirac or a Majorana particle. It is an alternative mode of the two-neutrinos double β decay, a rare decay which have been precisely measured by CUORE in the 130Te. We found no evidence of the 0νββ and we set a Bayesian lower limit of 2.2 ×1025yr on its half-life. The expertise achieved by CUORE set a milestone for any future bolometric detector, including CUPID, which is the planned next generation experiment searching for 0νββ with scintillating bolometers.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first cryogenic experiment searching for 0 νββ decay that has been able to reach the one-tonne mass scale. The detector, located at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, consists of an array of 988 TeO 2 crystals arranged in a compact cylindrical structure of 19 towers. CUORE began its first physics data run in 2017 at a base temperature of about 10 mK and in April 2021 released its 3 rd result of the search for 0 νββ, corresponding to a tonne-year of TeO 2 exposure. This is the largest amount of data ever acquired with a solid state detector and the most sensitive measurement of 0 νββ decay in 130Te ever conducted. We present the current status of CUORE search for 0 νββ with the updated statistics of one tonne-yr. We finally give an update of the CUORE background model and the measurement of the 130Te 2 νββ decay half-life and decay to excited states of 130Xe , studies performed using an exposure of 300.7 kg yr.

The CUORE experiment is a ton-scale array of TeO 2 cryogenic bolometers located at the underground Laboratori Nazionali del Gran Sasso of Istituto Nazionale di Fisica Nucleare (INFN), in Italy. The CUORE detector consists of 988 crystals operated as source and detector at a base temperature of ∼ 10 mK. Such cryogenic temperature is reached and maintained by means of a custom built cryogen-free dilution cryostat, designed with the aim of minimizing the vibrational noise and the environmental radioactivity. The primary goal of CUORE is the search for neutrinoless double beta decay of 130Te , but thanks to its large target mass and ultra-low background it is suitable for the study of other rare processes as well, such as the neutrinoless double beta decay of 128Te. This tellurium isotope is an attractive candidate for the search of this process, due to its high natural isotopic abundance of 31.75%. The transition energy at (866.7 ± 0.7) keV lies in a highly populated region of the energy spectrum, dominated by the contribution of the two-neutrino double beta decay of 130Te. As the first ton-scale infrastructure operating cryogenic TeO 2 bolometers in stable conditions, CUORE is able to achieve a factor > 10 higher sensitivity to the neutrinoless double beta decay of this isotope with respect to past direct experiments.

CUORE Upgrade with Particle IDentification (CUPID) is a foreseen ton-scale array of Li2MoO4 (LMO) cryogenic calorimeters with double readout of heat and light signals. Its scientific goal is to fully explore the inverted hierarchy of neutrino masses in the search for neutrinoless double beta decay of 100Mo. Pile-up of standard double beta decay of the candidate isotope is a relevant background. We generate pile-up heat events via injection of Joule heater pulses with a programmable waveform generator in a small array of LMO crystals operated underground in the Laboratori Nazionali del Gran Sasso, Italy. This allows to label pile-up pulses and control both time difference and underlying amplitudes of individual heat pulses in the data. We present the performance of supervised learning classifiers on data and the attained pile-up rejection efficiency.

The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νββ) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νββ decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νββ decay half-life of T_{1/2}>3.6×10^{24}  yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the most sensitive experiment searching for neutrinoless double-beta decay (0νββ) in 130Te. CUORE uses a cryogenic array of 988 TeO2 calorimeters operated at ∼10 mK with a total mass of 741 kg. To further increase the sensitivity, the detector response must be well understood. Here, we present a non-linear thermal model for the CUORE experiment on a detector-by-detector basis. We have examined both equilibrium and dynamic electro-thermal models of detectors by numerically fitting non-linear differential equations to the detector data of a subset of CUORE channels which are well characterized and representative of all channels. We demonstrate that the hot-electron effect and electric-field dependence of resistance in NTD-Ge thermistors alone are inadequate to describe our detectors' energy-dependent pulse shapes. We introduce an empirical second-order correction factor in the exponential temperature dependence of the thermistor, which produces excellent agreement with energy-dependent pulse shape data up to 6 MeV. We also present a noise analysis using the fitted thermal parameters and show that the intrinsic thermal noise is negligible compared to the observed noise for our detectors.

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT).MethodsPatients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation).ResultsThe two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p

The Cryogenic Underground Observatory for Rare Events (CUORE) is a large-scale cryogenic experiment searching for neutrinoless double-beta decay (0νββ) in Te130. The CUORE detector is made of natural tellurium, providing the possibility of rare event searches on isotopes other than Te130. In this work we describe a search for neutrinoless positron-emitting electron capture (β+EC) decay in Te120 with a total TeO2 exposure of 355.7 kg yr, corresponding to 0.2405 kg yr of Te120. Albeit 0νββ with two final-state electrons represents the most promising channel, the emission of a positron and two 511-keV γ's make 0νβ+EC decay signature extremely clear. To fully exploit the potential offered by the detector modularity we include events with different topology and perform a simultaneous fit of five selected signal signatures. Using blinded data we extract a median exclusion sensitivity of 3.4×1022 yr at 90% credibility interval (C.I.). After unblinding we find no evidence of 0νβ+EC signal and set a 90% C.I. Bayesian lower limit of 2.9×1022 yr on Te120 half-life. This result improves by an order of magnitude the existing limit from the combined analysis of CUORE-0 and Cuoricino.

The possibility that neutrinos may be their own antiparticles, unique among the known fundamental particles, arises from the symmetric theory of fermions proposed by Ettore Majorana in 19371. Given the profound consequences of such Majorana neutrinos, among which is a potential explanation for the matter-antimatter asymmetry of the universe via leptogenesis2, the Majorana nature of neutrinos commands intense experimental scrutiny globally; one of the primary experimental probes is neutrinoless double beta (0νββ) decay. Here we show results from the search for 0νββ decay of 130Te, using the latest advanced cryogenic calorimeters with the CUORE experiment3. CUORE, operating just 10 millikelvin above absolute zero, has pushed the state of the art on three frontiers: the sheer mass held at such ultralow temperatures, operational longevity, and the low levels of ionizing radiation emanating from the cryogenic infrastructure. We find no evidence for 0νββ decay and set a lower bound of the process half-life as 2.2 × 1025 years at a 90 per cent credibility interval. We discuss potential applications of the advances made with CUORE to other fields such as direct dark matter, neutrino and nuclear physics searches and large-scale quantum computing, which can benefit from sustained operation of large payloads in a low-radioactivity, ultralow-temperature cryogenic environment.

The CUORE experiment is searching for the neutrinoless double β decay of the 130Te using cryogenic calorimeters. The CUORE detector consists of 988 TeO2 crystals packed in 19 towers and placed in a cryogenic facility with a base temperature of 10 mK. Crystals are enriched in the isotope 130Te which is the candidate for the neutrinoless double β decay. It is taking data since 2017 at the Laboratori Nazionali del Gran Sasso in Italy. Such a long operation of a bolometric experiment in stable condition has no precedent: by reaching 1 tonne-year of exposure CUORE set a fundamental milestone for any future experiment using this technology. The CUORE collaboration investigated the neutrinoless double β decay of 130Te exploiting the updated 1 tonne-year of statistics, setting a limit of 2.2 × 1025 yr at the 90% of credibility interval on the half-life, with a median sensitivity of 2.8 × 1025 yr.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment searching for neutrino-less double-beta (0νββ) decay that has been able to reach the one-ton scale. The detector, located at the Laboratori Nazionali del Gran Sasso in Italy, consists of an array of 988 TeO2 crystals arranged in a compact cylindrical structure of 19 towers. Following the completion of the detector construction in August 2016, CUORE began its first physics data run in 2017 at a base temperature of about 10 mK. Following multiple optimization campaigns in 2018, CUORE is currently in stable operating mode. In 2019, CUORE released its second result of the search for 0νββ corresponding to a TeO2 exposure of 372.5 kgyr and a median exclusion sensitivity to a 130Te 0νββ decay half-life of 1.7 1025 yr. We find no evidence for 0νββ decay and set a 90% C.I. Bayesian lower limit of 3.2 1025 yr on the 130Te 0νββ decay half-life. We present the current status of CUORE's search for 0νββ. We give an update of the CUORE background model and the measurement of the 130Te two neutrino double-beta (2νββ) decay half-life. Eventually, we show the preliminary results on half-life limits from the analysis of 130Te 0νββ and 2νββ decay to the first 0+ excited state of 130Xe.

CUPID will be a next generation experiment searching for the neutrinolessdouble $\beta$ decay, whose discovery would establish the Majorana nature ofthe neutrino. Based on the experience achieved with the CUORE experiment,presently taking data at LNGS, CUPID aims to reach a background freeenvironment by means of scintillating Li$_{2}$$^{100}$MoO$_4$ crystals coupledto light detectors. Indeed, the simultaneous heat and light detection allows usto reject the dominant background of $\alpha$ particles, as proven by theCUPID-0 and CUPID-Mo demonstrators. In this work we present the results of thefirst test of the CUPID baseline module. In particular, we propose a newoptimized detector structure and light sensors design to enhance theengineering and the light collection, respectively. We characterized the heatdetectors, achieving an energy resolution of (5.9 $\pm$ 0.2) keV FWHM at the$Q$-value of $^{100}$Mo (about 3034 keV). We studied the light collection ofthe baseline CUPID design with respect to an alternative configuration whichfeatures gravity-assisted light detectors' mounting. In both cases we obtainedan improvement in the light collection with respect to past measures and wevalidated the particle identification capability of the detector, which ensuresan $\alpha$ particle rejection higher than 99.9%, fully satisfying therequirements for CUPID.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

CUPID will be a next generation experiment searching for the neutrinoless double β decay, whose discovery would establish the Majorana nature of the neutrino. Based on the experience achieved with the CUORE experiment, presently taking data at LNGS, CUPID aims to reach a background free environment by means of scintillating Li2100MoO4 crystals coupled to light detectors. Indeed, the simultaneous heat and light detection allows us to reject the dominant background of α particles, as proven by the CUPID-0 and CUPID-Mo demonstrators. In this work we present the results of the first test of the CUPID baseline module. In particular, we propose a new optimized detector structure and light sensors design to enhance the engineering and the light collection, respectively. We characterized the heat detectors, achieving an energy resolution of (5.9 ± 0.2) keV FWHM at the Q-value of 100Mo (about 3034 keV). We studied the light collection of the baseline CUPID design with respect to an alternative configuration which features gravity-assisted light detectors’ mounting. In both cases we obtained an improvement in the light collection with respect to past measures and we validated the particle identification capability of the detector, which ensures an α particle rejection higher than 99.9%, fully satisfying the requirements for CUPID.

Machine learning (ML) and artificial intelligence (AI) algorithms have the potential to derive insights from clinical data and improve patient outcomes. However, these highly complex systems are sensitive to changes in the environment and liable to performance decay. Even after their successful integration into clinical practice, ML/AI algorithms should be continuously monitored and updated to ensure their long-term safety and effectiveness. To bring AI into maturity in clinical care, we advocate for the creation of hospital units responsible for quality assurance and improvement of these algorithms, which we refer to as "AI-QI" units. We discuss how tools that have long been used in hospital quality assurance and quality improvement can be adapted to monitor static ML algorithms. On the other hand, procedures for continual model updating are still nascent. We highlight key considerations when choosing between existing methods and opportunities for methodological innovation.

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution – comparable to semiconductor detectors – and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined.

CUPID is the next generation experiment which will use scintillating cryogenic calorimeters to search for the neutrinoless double β decay. This unobserved process would shed light on the nature of the neutrino, which up to our knowledge could be a Majorana or a Dirac particle, and would give us an important hint to explain the lack of antimatter in the universe. This ambitious search needs a detector with unique characteristics such as an extremely low background level and an excellent energy resolution. CUPID is now in advanced R&D state to optimize the detector design in order to completely exploit the potentialities of scintillating cryogenic calorimeters. In the following I will describe the test performed at the LNGS (Laboratori Nazionali del Gran Sasso) of a single module of the future CUPID detector. In this contribution we present the performance obtained with a novel assembly concept, proving that it matches the requirements for CUPID.

In the past few years, attention has been drawn to the fact that a precision analysis of two-neutrino double beta decay (2νββ) allows the study of interesting physics cases like the emission of Majoron bosons and possible Lorentz symmetry violation. These processes modify the summed-energy distribution of the two electrons emitted in 2νββ. CUPID is a next-generation experiment aiming to exploit 100Mo-enriched scintillating Li2MoO4 crystals, operating as cryogenic calorimeters. Given the relatively fast half-life of 100Mo 2νββ and the large exposure that can be reached by CUPID, we expect to measure with very high precision the 100Mo 2νββ spectrum shape, reaching great sensitivities in the search for distortions induced by the physics beyond the Standard Model. In this contribution, we present the CUPID exclusion sensitivity for such New Physics processes, as well as the preliminary projected background of CUPID.

ObjectiveIn a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.MethodsWe performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.ResultsWe replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.ConclusionCollectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.

Precise characterization of detector time resolution is of crucial importance for next-generation cryogenic-bolometer experiments searching for neutrinoless double-beta decay, such as CUPID, in order to reject background due to pileup of two-neutrino double-beta decay events. In this paper, we describe a technique developed to study the pileup rejection capability of cryogenic bolometers. Our approach, which consists of producing controlled pileup events with a programmable wave-form generator, has the benefit that we can reliably and reproducibly control the time separation and relative energy of the individual components of the generated pileup events. The resulting data allow us to optimize and benchmark analysis strategies to discriminate between individual and pileup pulses. We describe a test of this technique performed with a small array of detectors at the Laboratori Nazionali del Gran Sasso, in Italy; we obtain a 90% rejection efficiency against pulser-generated pileup events with rise time of ∼15ms down to time separation between the individual events of about 2ms.

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay (0 νββ) in the isotope 130Te. In this work we present the latest results on two searches for the double beta decay (DBD) of 130Te to the first 02+ excited state of 130Xe : the 0 νββ decay and the Standard Model-allowed two-neutrinos double beta decay (2 νββ). Both searches are based on a 372.5 kg× yr TeO2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as S1/20ν=5.6×1024yr for the 0 νββ decay and S1/22ν=2.1×1024yr for the 2 νββ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at 90 % C.I. on the decay half lives is obtained as: (T1/2)02+0ν>5.9×1024yr for the 0 νββ mode and (T1/2)02+2ν>1.3×1024yr for the 2 νββ mode. These represent the most stringent limits on the DBD of 130Te to excited states and improve by a factor ∼ 5 the previous results on this process.

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay (0 νββ) in the isotope 130Te. In this work we present the latest results on two searches for the double beta decay (DBD) of 130Te to the first 02+ excited state of 130Xe : the 0 νββ decay and the Standard Model-allowed two-neutrinos double beta decay (2 νββ). Both searches are based on a 372.5 kg× yr TeO2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as S1/20ν=5.6×1024yr for the 0 νββ decay and S1/22ν=2.1×1024yr for the 2 νββ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at 90 % C.I. on the decay half lives is obtained as: (T1/2)02+0ν>5.9×1024yr for the 0 νββ mode and (T1/2)02+2ν>1.3×1024yr for the 2 νββ mode. These represent the most stringent limits on the DBD of 130Te to excited states and improve by a factor ∼ 5 the previous results on this process.

Precise characterization of detector time resolution is of crucial importance for next-generation cryogenic-bolometer experiments searching for neutrinoless double-beta decay, such as CUPID, in order to reject background due to pileup of two-neutrino double-beta decay events. In this paper, we describe a technique developed to study the pileup rejection capability of cryogenic bolometers. Our approach, which consists of producing controlled pileup events with a programmable wave-form generator, has the benefit that we can reliably and reproducibly control the time separation and relative energy of the individual components of the generated pileup events. The resulting data allow us to optimize and benchmark analysis strategies to discriminate between individual and pileup pulses. We describe a test of this technique performed with a small array of detectors at the Laboratori Nazionali del Gran Sasso, in Italy; we obtain a 90% rejection efficiency against pulser-generated pileup events with rise time of ∼15ms down to time separation between the individual events of about 2ms.

BackgroundMany pregnant people find no bridge to ongoing specialty or primary care after giving birth, even when clinical and social complications of pregnancy signal need. Black, indigenous, and all other women of color are especially harmed by fragmented care and access disparities, coupled with impacts of racism over the life course and in health care.MethodsWe launched the initiative "Bridging the Chasm between Pregnancy and Health across the Life Course" in 2018, bringing together patients, advocates, providers, researchers, policymakers, and systems innovators to create a National Agenda for Research and Action. We held a 2-day conference that blended storytelling, evidence analysis, and consensus building to identify key themes related to gaps in care and root causes of inequities. In 2019, more than 70 stakeholders joined six working groups to reach consensus on strategic priorities based on equity, innovation, effectiveness, and feasibility.FindingsWorking groups identified six key strategic areas for bridging the chasm. These include: 1) progress toward eliminating institutional and interpersonal racism and bias as a requirement for accreditation of health care institutions, 2) infrastructure support for community-based organizations, 3) extension of holistic team-based care to the postpartum year and beyond, with integration of doulas and community health workers on the team, 4) extension of Medicaid coverage and new quality and pay-for-performance metrics to link maternity care and primary care, 5) systems to preserve maternal narratives and data across providers, and 6) alignment of research with women's lived experiences.ConclusionsThe resulting agenda presents a path forward to remedy the structural chasms in women's health care, with key roles for advocates, policymakers, researchers, health care leaders, educators, and the media.

Despite being the feeblest and lightest of the known particles, the neutrinois one of the most abundant particles in the Universe and has played a criticalrole in its evolution. Within standard cosmological models, most of theneutrinos were produced in the Big Bang and completely decoupled from matterafter the first second. During that short time it is possible that through theprocess of Leptogenesis neutrinos helped to produce the matter/anti-matterasymmetry that sets the stage for all of the structures that we see in theuniverse today. However, these theories generally require the condition thatthe neutrino is a so-called Majorana particle, acting as its own anti-particle.The search for the extremely rare neutrinoless double-beta $(0\nu\beta\beta)$decay is currently the most practical way to address this question. Here wepresent the results of the first tonne-year exposure search for$0\nu\beta\beta$ decay of $^{130}$Te with CUORE. With a median half-lifeexclusion sensitivity of $2.8\times10^{25}$ yr, this is the most sensitivesearch for $0\nu\beta\beta$ decay in $^{130}$Te to date. We find no evidencefor $0\nu\beta\beta$ decay and set a lower bound of $T_{1/2} >2.2\times10^{25}$ yr at a 90% credibility interval. CUORE is the largest,coldest solid-state detector operating below 100mK in the world. Theachievement of 1 tonne-year of exposure demonstrates the long-term reliabilityand potential of cryogenic technology at this scale, with wide rangingapplications to next-generation rare-event searches, dark matter searches, andeven large-scale quantum computing.

A scintillating bolometer based on a large cubic Li$_{2}$$^{100}$MoO$_4$crystal (45 mm side) and a Ge wafer (scintillation detector) has been operatedin the CROSS cryogenic facility at the Canfranc underground laboratory inSpain. The dual-readout detector is a prototype of the technology that will beused in the next-generation $0\nu2\beta$ experiment CUPID. The measurementswere performed at 18 and 12 mK temperature in a pulse tube dilutionrefrigerator. This setup utilizes the same technology as the CUORE cryostatthat will host CUPID and so represents an accurate estimation of the expectedperformance. The Li$_{2}$$^{100}$MoO$_4$ bolometer shows a high energyresolution of 6 keV FWHM at the 2615 keV $\gamma$ line. The detection ofscintillation light for each event triggered by the Li$_{2}$$^{100}$MoO$_4$bolometer allowed for a full separation ($\sim$8$\sigma$) between$\gamma$($\beta$) and $\alpha$ events above 2 MeV. The Li$_{2}$$^{100}$MoO$_4$crystal also shows a high internal radiopurity with $^{228}$Th and $^{226}$Raactivities of less than 3 and 8 $\mu$Bq/kg, respectively. Taking also intoaccount the advantage of a more compact and massive detector array, which canbe made of cubic-shaped crystals (compared to the cylindrical ones), this testdemonstrates the great potential of cubic Li$_{2}$$^{100}$MoO$_4$ scintillatingbolometers for high-sensitivity searches for the $^{100}$Mo $0\nu2\beta$ decayin CROSS and CUPID projects.

A scintillating bolometer based on a large cubic Li$_{2}$$^{100}$MoO$_4$crystal (45 mm side) and a Ge wafer (scintillation detector) has been operatedin the CROSS cryogenic facility at the Canfranc underground laboratory inSpain. The dual-readout detector is a prototype of the technology that will beused in the next-generation $0u2\beta$ experiment CUPID. The measurementswere performed at 18 and 12 mK temperature in a pulse tube dilutionrefrigerator. This setup utilizes the same technology as the CUORE cryostatthat will host CUPID and so represents an accurate estimation of the expectedperformance. The Li$_{2}$$^{100}$MoO$_4$ bolometer shows a high energyresolution of 6 keV FWHM at the 2615 keV $\gamma$ line. The detection ofscintillation light for each event triggered by the Li$_{2}$$^{100}$MoO$_4$bolometer allowed for a full separation ($\sim$8$\sigma$) between$\gamma$($\beta$) and $\alpha$ events above 2 MeV. The Li$_{2}$$^{100}$MoO$_4$crystal also shows a high internal radiopurity with $^{228}$Th and $^{226}$Raactivities of less than 3 and 8 $\mu$Bq/kg, respectively. Taking also intoaccount the advantage of a more compact and massive detector array, which canbe made of cubic-shaped crystals (compared to the cylindrical ones), this testdemonstrates the great potential of cubic Li$_{2}$$^{100}$MoO$_4$ scintillatingbolometers for high-sensitivity searches for the $^{100}$Mo $0u2\beta$ decayin CROSS and CUPID projects.

A scintillating bolometer based on a large cubic Li2100MoO4 crystal (45 mm side) and a Ge wafer (scintillation detector) has been operated in the CROSS cryogenic facility at the Canfranc underground laboratory in Spain. The dual-readout detector is a prototype of the technology that will be used in the next-generation 0ν2β experiment CUPID . The measurements were performed at 18 and 12 mK temperature in a pulse tube dilution refrigerator. This setup utilizes the same technology as the CUORE cryostat that will host CUPID and so represents an accurate estimation of the expected performance. The Li2100MoO4 bolometer shows a high energy resolution of 6 keV FWHM at the 2615 keV γ line. The detection of scintillation light for each event triggered by the Li2100MoO4 bolometer allowed for a full separation (∼8σ) between γ(β) and α events above 2 MeV . The Li2100MoO4 crystal also shows a high internal radiopurity with 228Th and 226Ra activities of less than 3 and 8 μBq/kg, respectively. Taking also into account the advantage of a more compact and massive detector array, which can be made of cubic-shaped crystals (compared to the cylindrical ones), this test demonstrates the great potential of cubic Li2100MoO4 scintillating bolometers for high-sensitivity searches for the 100Mo 0ν2β decay in CROSS and CUPID projects.

The CUPID Collaboration is designing a tonne-scale, background-free detector to search for double beta decay with sufficient sensitivity to fully explore the parameter space corresponding to the inverted neutrino mass hierarchy scenario. One of the CUPID demonstrators, CUPID-Mo, has proved the potential of enriched Li2100MoO4 crystals as suitable detectors for neutrinoless double beta decay search. In this work, we characterised cubic crystals that, compared to the cylindrical crystals used by CUPID-Mo, are more appealing for the construction of tightly packed arrays. We measured an average energy resolution of (6.7 ± 0.6) keV FWHM in the region of interest, approaching the CUPID target of 5 keV FWHM. We assessed the identification of α particles with and without a reflecting foil that enhances the scintillation light collection efficiency, proving that the baseline design of CUPID already ensures a complete suppression of this α-induced background contribution. We also used the collected data to validate a Monte Carlo simulation modelling the light collection efficiency, which will enable further optimisations of the detector.

The CUPID Collaboration is designing a tonne-scale, background-free detectorto search for double beta decay with sufficient sensitivity to fully explorethe parameter space corresponding to the inverted neutrino mass hierarchyscenario. One of the CUPID demonstrators, CUPID-Mo, has proved the potential ofenriched Li$_{2}$$^{100}$MoO$_4$ crystals as suitable detectors forneutrinoless double beta decay search. In this work, we characterised cubiccrystals that, compared to the cylindrical crystals used by CUPID-Mo, are moreappealing for the construction of tightly packed arrays. We measured an averageenergy resolution of (6.7$\pm$0.6) keV FWHM in the region of interest,approaching the CUPID target of 5 keV FWHM. We assessed the identification of$\alpha$ particles with and without a reflecting foil that enhances thescintillation light collection efficiency, proving that the baseline design ofCUPID already ensures a complete suppression of this $\alpha$-inducedbackground contribution. We also used the collected data to validate a MonteCarlo simulation modelling the light collection efficiency, which will enablefurther optimisations of the detector.

A scintillating bolometer based on a large cubic Li2100MoO4 crystal (45 mm side) and a Ge wafer (scintillation detector) has been operated in the CROSS cryogenic facility at the Canfranc underground laboratory in Spain. The dual-readout detector is a prototype of the technology that will be used in the next-generation 0ν2β experiment CUPID . The measurements were performed at 18 and 12 mK temperature in a pulse tube dilution refrigerator. This setup utilizes the same technology as the CUORE cryostat that will host CUPID and so represents an accurate estimation of the expected performance. The Li2100MoO4 bolometer shows a high energy resolution of 6 keV FWHM at the 2615 keV γ line. The detection of scintillation light for each event triggered by the Li2100MoO4 bolometer allowed for a full separation (∼8σ) between γ(β) and α events above 2 MeV . The Li2100MoO4 crystal also shows a high internal radiopurity with 228Th and 226Ra activities of less than 3 and 8 μBq/kg, respectively. Taking also into account the advantage of a more compact and massive detector array, which can be made of cubic-shaped crystals (compared to the cylindrical ones), this test demonstrates the great potential of cubic Li2100MoO4 scintillating bolometers for high-sensitivity searches for the 100Mo 0ν2β decay in CROSS and CUPID projects.

The CUPID Collaboration is designing a tonne-scale, background-free detector to search for double beta decay with sufficient sensitivity to fully explore the parameter space corresponding to the inverted neutrino mass hierarchy scenario. One of the CUPID demonstrators, CUPID-Mo, has proved the potential of enriched Li2100MoO4 crystals as suitable detectors for neutrinoless double beta decay search. In this work, we characterised cubic crystals that, compared to the cylindrical crystals used by CUPID-Mo, are more appealing for the construction of tightly packed arrays. We measured an average energy resolution of (6.7 ± 0.6) keV FWHM in the region of interest, approaching the CUPID target of 5 keV FWHM. We assessed the identification of α particles with and without a reflecting foil that enhances the scintillation light collection efficiency, proving that the baseline design of CUPID already ensures a complete suppression of this α-induced background contribution. We also used the collected data to validate a Monte Carlo simulation modelling the light collection efficiency, which will enable further optimisations of the detector.

The CUORE experiment is a large bolometric array searching for the leptonnumber violating neutrino-less double beta decay ($0u\beta\beta$) in theisotope $\mathrm{^{130}Te}$. In this work we present the latest results on twosearches for the double beta decay (DBD) of $\mathrm{^{130}Te}$ to the first$0^{+}_2$ excited state of $\mathrm{^{130}Xe}$: the $0u\beta\beta$ decay andthe Standard Model-allowed two-neutrinos double beta decay ($2u\beta\beta$).Both searches are based on a 372.5 kg$\times$yr TeO$_2$ exposure. Thede-excitation gamma rays emitted by the excited Xe nucleus in the final stateyield a unique signature, which can be searched for with low background bystudying coincident events in two or more bolometers. The closely packedarrangement of the CUORE crystals constitutes a significant advantage in thisregard. The median limit setting sensitivities at 90\% Credible Interval (C.I.)of the given searches were estimated as $\mathrm{S^{0u}_{1/2} = 5.6 \times10^{24} \: \mathrm{yr}}$ for the ${0u\beta\beta}$ decay and$\mathrm{S^{2u}_{1/2} = 2.1 \times 10^{24} \: \mathrm{yr}}$ for the${2u\beta\beta}$ decay. No significant evidence for either of the decay modeswas observed and a Bayesian lower bound at $90\%$ C.I. on the decay half livesis obtained as: $\mathrm{(T_{1/2})^{0u}_{0^+_2} > 5.9 \times 10^{24} \:\mathrm{yr}}$ for the $0u\beta\beta$ mode and$\mathrm{(T_{1/2})^{2u}_{0^+_2} > 1.3 \times 10^{24} \: \mathrm{yr}}$ for the$2u\beta\beta$ mode. These represent the most stringent limits on the DBD of$^{130}$Te to excited states and improve by a factor $\sim5$ the previousresults on this process.

The CUORE experiment is a large bolometric array searching for the leptonnumber violating neutrino-less double beta decay ($0\nu\beta\beta$) in theisotope $\mathrm{^{130}Te}$. In this work we present the latest results on twosearches for the double beta decay (DBD) of $\mathrm{^{130}Te}$ to the first$0^{+}_2$ excited state of $\mathrm{^{130}Xe}$: the $0\nu\beta\beta$ decay andthe Standard Model-allowed two-neutrinos double beta decay ($2\nu\beta\beta$).Both searches are based on a 372.5 kg$\times$yr TeO$_2$ exposure. Thede-excitation gamma rays emitted by the excited Xe nucleus in the final stateyield a unique signature, which can be searched for with low background bystudying coincident events in two or more bolometers. The closely packedarrangement of the CUORE crystals constitutes a significant advantage in thisregard. The median limit setting sensitivities at 90\% Credible Interval (C.I.)of the given searches were estimated as $\mathrm{S^{0\nu}_{1/2} = 5.6 \times10^{24} \: \mathrm{yr}}$ for the ${0\nu\beta\beta}$ decay and$\mathrm{S^{2\nu}_{1/2} = 2.1 \times 10^{24} \: \mathrm{yr}}$ for the${2\nu\beta\beta}$ decay. No significant evidence for either of the decay modeswas observed and a Bayesian lower bound at $90\%$ C.I. on the decay half livesis obtained as: $\mathrm{(T_{1/2})^{0\nu}_{0^+_2} > 5.9 \times 10^{24} \:\mathrm{yr}}$ for the $0\nu\beta\beta$ mode and$\mathrm{(T_{1/2})^{2\nu}_{0^+_2} > 1.3 \times 10^{24} \: \mathrm{yr}}$ for the$2\nu\beta\beta$ mode. These represent the most stringent limits on the DBD of$^{130}$Te to excited states and improve by a factor $\sim5$ the previousresults on this process.

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution – comparable to semiconductor detectors – and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined.

Precise characterization of detector time resolution is of crucial importancefor next-generation cryogenic-bolometer experiments searching for neutrinolessdouble-beta decay, such as CUPID, in order to reject background due to pile-upof two-neutrino double-beta decay events. In this paper, we describe atechnique developed to study the pile-up rejection capability of cryogenicbolometers. Our approach, which consists of producing controlled pile-up eventswith a programmable waveform generator, has the benefit that we can reliablyand reproducibly control the time separation and relative energy of theindividual components of the generated pile-up events. The resulting data allowus to optimize and benchmark analysis strategies to discriminate betweenindividual and pile-up pulses. We describe a test of this technique performedwith a small array of detectors at the Laboratori Nazionali del Gran Sasso, inItaly; we obtain a 90% rejection efficiency against pulser-generated pile-upevents with rise time of ~15ms down to time separation between the individualevents of about 2ms.

Precise characterization of detector time resolution is of crucial importancefor next-generation cryogenic-bolometer experiments searching for neutrinolessdouble-beta decay, such as CUPID, in order to reject background due to pile-upof two-neutrino double-beta decay events. In this paper, we describe atechnique developed to study the pile-up rejection capability of cryogenicbolometers. Our approach, which consists of producing controlled pile-up eventswith a programmable waveform generator, has the benefit that we can reliablyand reproducibly control the time separation and relative energy of theindividual components of the generated pile-up events. The resulting data allowus to optimize and benchmark analysis strategies to discriminate betweenindividual and pile-up pulses. We describe a test of this technique performedwith a small array of detectors at the Laboratori Nazionali del Gran Sasso, inItaly; we obtain a 90% rejection efficiency against pulser-generated pile-upevents with rise time of ~15ms down to time separation between the individualevents of about 2ms.