Measurement of the 2νßß Decay Half-Life of

We report on the results obtained with the global CUPID-0 background model, which combines the data collected in the two measurement campaigns for a total exposure of 8.82 kg×yr of ^{82}Se. We identify with improved precision the background sources within the 3 MeV energy region, where neutrinoless double ß decay of ^{82}Se and ^{100}Mo is expected, making more solid the foundations for the background budget of the next-generation CUPID experiment. Relying on the excellent data reconstruction, we measure the two-neutrino double ß-decay half-life of ^{82}Se with unprecedented accuracy: T_{1/2}^{2ν}=[8.69±0.05(stat)_{-0.06}^{+0.09}(syst)]×10^{19} yr.

Final Result on the Neutrinoless Double Beta Decay of

CUPID-0, an array of Zn^{82}Se cryogenic calorimeters, was the first medium-scale demonstrator of the scintillating bolometers' technology. The first project phase (March 2017-December 2018) allowed the most stringent limit on the neutrinoless double beta decay half-life of the isotope of interest, ^{82}Se, to be set. After a six month long detector upgrade, CUPID-0 began its second and last phase (June 2019-February 2020). In this Letter, we describe the search for neutrinoless double beta decay of ^{82}Se with a total exposure (phase I+II) of 8.82 kg yr^{-1} of isotope. We set a limit on the half-life of ^{82}Se to the ground state of ^{82}Kr of T_{1/2}^{0ν}(^{82}Se)>4.6×10^{24} yr (90% credible interval), corresponding to an effective Majorana neutrino mass m_{ßß}<(263-545) meV. We also set the most stringent lower limits on the neutrinoless decays of ^{82}Se to the 0_{1}^{+}, 2_{1}^{+}, and 2_{2}^{+} excited states of ^{82}Kr, finding 1.8×10^{23} yr, 3.0×10^{23} yr, and 3.2×10^{23} yr (90% credible interval) respectively.

Angular Momentum Removal by Neutron and γ-Ray Emissions during Fission Fragment Decays.

We investigate the angular momentum removal from fission fragments (FFs) through neutron and γ-ray emission, finding that about half the neutrons are emitted with angular momenta ≥1.5ℏ and that the change in angular momentum after the emission of neutrons and statistical γ rays is significant, contradicting usual assumptions. Per fission event, in our simulations, the neutron and statistical γ-ray emissions change the spin of the fragment by 3.5-5ℏ, with a large standard deviation comparable to the average value. Such wide angular momentum removal distributions can hide any underlying correlations in the fission fragment initial spin values. Within our model, we reproduce data on spin measurements from discrete transitions after neutron emissions, especially in the case of light FFs. The agreement further improves for the heavy fragments if one removes from the analysis the events that would produce isomeric states. Finally, we show that while in our model the initial FF spins do not follow a sawtoothlike behavior observed in recent measurements, the average FF spin computed after neutron and statistical γ emissions exhibits a shape that resembles a sawtooth. This suggests that the average FF spin measured after statistical emissions is not necessarily connected with the scission mechanism as previously implied.

Final Result of CUPID-0 Phase-I in the Search for the

CUPID-0 is the first pilot experiment of CUPID, a next-generation project for the measurement of neutrinoless double beta decay (0νDBD) with scintillating bolometers. The detector, consisting of 24 enriched and 2 natural ZnSe crystals, has been taking data at Laboratori Nazionali del Gran Sasso from June 2017 to December 2018, collecting a ^{82}Se exposure of 5.29 kg×yr. In this Letter we present the phase-I results in the search for 0νDBD. We demonstrate that the technology implemented by CUPID-0 allows us to reach the lowest background for calorimetric experiments: (3.5_{-0.9}^{+1.0})×10^{-3} counts/(keV kg yr). Monitoring 3.88×10^{25} ^{82}Se nuclei×yr we reach a 90% credible interval median sensitivity of T_{1/2}^{0ν}>5.0×10^{24} yr and set the most stringent limit on the half-life of ^{82}Se 0νDBD: T_{1/2}^{0ν}>3.5×10^{24} yr (90% credible interval), corresponding to m_{ßß}<(311-638) meV depending on the nuclear matrix element calculations.

Evidence of Single State Dominance in the Two-Neutrino Double-ß Decay of

We report on the measurement of the two-neutrino double-ß decay of ^{82}Se performed for the first time with cryogenic calorimeters, in the framework of the CUPID-0 experiment. With an exposure of 9.95 kg yr of Zn^{82}Se, we determine the two-neutrino double-ß decay half-life of ^{82}Se with an unprecedented precision level, T_{1/2}^{2ν}=[8.60±0.03(stat) _{-0.13}^{+0.19}(syst)]×10^{19} yr. The very high signal-to-background ratio, along with the detailed reconstruction of the background sources allowed us to identify the single state dominance as the underlying mechanism of such a process, demonstrating that the higher state dominance hypothesis is disfavored at the level of 5.5σ.

First Result on the Neutrinoless Double-ß Decay of

We report the result of the search for neutrinoless double beta decay of ^{82}Se obtained with CUPID-0, the first large array of scintillating Zn^{82}Se cryogenic calorimeters implementing particle identification. We observe no signal in a 1.83 kg yr ^{82}Se exposure, and we set the most stringent lower limit on the 0νßß ^{82}Se half-life T_{1/2}^{0ν}>2.4×10^{24} yr (90% credible interval), which corresponds to an effective Majorana neutrino mass m_{ßß}<(376-770) meV depending on the nuclear matrix element calculations. The heat-light readout provides a powerful tool for the rejection of α particles and allows us to suppress the background in the region of interest down to (3.6_{-1.4}^{+1.9})×10^{-3} counts/(keV kg yr), an unprecedented level for this technique.

MeV-energy x rays from inverse compton scattering with laser-wakefield accelerated electrons.

We report the generation of MeV x rays using an undulator and accelerator that are both driven by the same 100-terawatt laser system. The laser pulse driving the accelerator and the scattering laser pulse are independently optimized to generate a high energy electron beam (>200 MeV) and maximize the output x-ray brightness. The total x-ray photon number was measured to be ∼1×10(7), the source size was 5 µm, and the beam divergence angle was ∼10 mrad. The x-ray photon energy, peaked at 1 MeV (reaching up to 4 MeV), exceeds the thresholds of fundamental nuclear processes (e.g., pair production and photodisintegration).

Detecting and characterizing special nuclear material for nuclear nonproliferation applications.

There is an urgent need for new, better instrumentation and techniques for detecting and characterizing special nuclear material (SNM), i.e., highly enriched uranium and plutonium. The development of improved instruments and techniques requires experiments performed with the SNM itself, which is of limited availability. This paper describes the findings of experiments performed at the National Criticality Experiments Research Center conducted using new instruments and techniques on unclassified, kg-quantity SNM objects. These experiments, performed in the framework of the Department of Energy, National Nuclear Security Administration Consortium for Monitoring, Technology, and Verification, focused on detecting, characterizing, and localizing SNM samples with masses ranging from 3.3 to 13.8 kg, including plutonium and highly enriched uranium using prototype detectors and techniques. The work demonstrates SNM detection and characterization using recently-developed prototype detection systems. Specifically, we present new results in passive detection and imaging of plutonium and uranium objects using gamma-ray and dual particle (fast neutron and gamma-ray) imaging. We also present a new analysis of the delayed neutron emissions during active interrogation of uranium using a neutron generator.

Characterization of a kg-scale archaeological lead-based PbWO4 cryogenic detector for the RES-NOVA experiment.

Core-collapse Supernovae (SNe) are one of the most energetic events in the Universe, during which almost all the star's binding energy is released in the form of neutrinos. These particles are direct probes of the processes occurring in the stellar core and provide unique insights into the gravitational collapse. RES-NOVA will revolutionize how we detect neutrinos from astrophysical sources, by deploying the first ton-scale array of cryogenic detectors made from archaeological lead. Pb offers the highest neutrino interaction cross-section via coherent elastic neutrino-nucleus scattering (CEνNS). Such process will enable RES-NOVA to be equally sensitive to all neutrino flavours. For the first time, we propose the use archaeological Pb as sensitive target material in order to achieve an ultra-low background level in the region of interest (O(1 keV)). All these features make possible the deployment of the first cm-scale neutrino telescope for the investigation of astrophysical sources. In this contribution, we will characterize the radiopurity level and the performance of a small-scale proof-of-principle detector of RES-NOVA, consisting in a PbWO4 crystal made from archaeological-Pb operated as cryogenic detector.

Metformin exposure affects human and mouse fetal testicular cells.

BACKGROUND: Metformin is a drug used in the treatment of diabetes and of some disorders related to insulin resistance, such as polycystic ovary syndrome. Gestational diabetes can cause complications for both mother and child, and some studies have shown a beneficial effect of metformin during pregnancy without an increase in perinatal complications. However, the effects on the gonads have not been properly studied. Here we investigated the effect of metformin administered during pregnancy on the development and function of the fetal testis. METHODS: A dual approach in vitro and in vivo using human and mouse models was chosen. Cultures of human and murine organotypic testes were made and in vivo embryonic testes were analysed after oral administration of metformin to pregnant mice. RESULTS: In human and mouse organotypic cultures in vitro, metformin decreased testosterone secretion and mRNA expression of the main factors involved in steroid production. In vitro, the lowest observed effect concentration (LOEC) on testosterone secretion was 50 µM in human, whereas it was 500 µM in mouse testis. Lactate secretion was increased in both human and mouse organotypic cultures with the same LOEC at 500 µM as observed in other cell culture models after metformin stimulation. In vivo administration of metformin to pregnant mice reduced the testicular size of the fetal and neonatal testes exposed to metformin during intrauterine life. Although the number of germ cells was not affected by the metformin treatment, the number of Sertoli cells, the nurse cells of germ cells, was slightly yet significantly reduced in both periods (fetal period: P = 0.007; neonatal period: P = 0.03). The Leydig cell population, which produces androgens, and the testosterone content were diminished only in the fetal period at 16 days post-coitum. CONCLUSIONS: This study showed a potentially harmful effect of metformin treatment on the development of the fetal testis and should encourage future human epidemiological studies.

Mechanical Stress Analysis of Different Configurations of the All-on-4 Concept in Atrophic Mandible: A 3D Finite Element Study.

PURPOSE: This study evaluated the mechanical behavior of different configurations of the All-on-4 treatment concept designed with straight short (6-mm-length), straight standard (11-mm-length), or tilted standard (30-degree angled; 11-mm-length) posterior implants. MATERIALS AND METHODS: The All-on-4 configurations were performed in atrophic mandible models and consisted of anterior straight standard and posterior tilted standard implants (H1 model), anterior straight standard and posterior straight short implants (H2 model), and anterior and posterior straight standard implants (H3 model). Three oblique forces of 100 N were simulated in the posterior region of the prosthetic bar. The values of stress were obtained for the ductile materials using the von Mises equivalent stress (σvm) criteria. The stress peaks in the peri-implant bone crest were measured by the maximum (σmax) and minimum (σmin) principal stresses. The two-way analysis of variance (two-way ANOVA) and Tukey post hoc tests determined significant differences (P < .01) of stress values among the ductile materials (implant and prosthetic components). RESULTS: The use of tilted standard posterior implants (H1 model) showed the lowest values of σmax and σmin in the posterior region of the peri-implant bone area. On the other hand, the use of straight short (H2 model) or straight standard (H3 model) posterior implants significantly reduced the von Mises mean stresses in the bar screws, abutments, and abutment screws (P < .01). CONCLUSION: The higher odds of technical failures (screw fracture/loosening) may be expected when the All-on-4 configuration is performed with tilted standard posterior implants. Also, peri-implant bone overload may occur when the All-on-4 design is performed with straight short or straight standard posterior implants in atrophic mandibles.

Background identification in cryogenic calorimeters through α - α delayed coincidences.

Localization and modeling of radioactive contaminations is a challenge that ultra-low background experiments are constantly facing. These are fundamental steps both to extract scientific results and to further reduce the background of the detectors. Here we present an innovative technique based on the analysis of α - α delayed coincidences in 232 Th and 238 U decay chains, developed to investigate the contaminations of the ZnSe crystals in the CUPID-0 experiment. This method allows to disentangle surface and bulk contaminations of the detectors relying on the different probability to tag delayed coincidences as function of the α decay position.

Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story.

BACKGROUND: Improved treatment have modified survival outcome in patients with diffuse large B-cell lymphoma (DLBCL) and altered the importance of previously recognized prognostic markers. DESIGN AND METHODS: To evaluate International Prognostic Index (IPI) score before and after rituximab introduction and to validate the absolute lymphocyte count (ALC)/revised International Prognostic Index (R-IPI) model, we carried out a retrospective analysis on a total of 831 patients with DLBCL. RESULTS: Our results show that IPI lost its discriminating power with the introduction of rituximab. The analysis of our second set allowed us to validate the ALC/R-IPI model. The R-IPI and ALC/R-IPI could still be used for designing clinical trials, but both have difficulty recognizing a high percentage of poor prognosis patients, though it remains an important goal of a good prognostic model considering the modest impact of salvage treatments on survival. CONCLUSIONS: A new model on the basis of significant variables in the rituximab era and built on a large database of patients treated with rituximab is urgently needed. As prognostic models are changing with the efficacy and mechanisms of action of treatment utilized, looking for a new prognostic score is a never-ending story in which researchers are trying to hit a continuously moving target.

DUAL-PARTICLE DOSEMETER BASED ON ORGANIC SCINTILLATOR.

Traditionally available handheld dosemeters are generally sensitive to only one type of radiation: neutrons or photons. Some dosemeters also rely on very specific attenuation correlations between response and dose, are not scalable in size and multiple dosemeters are required to characterise mixed-particle fields. The research presented here serves as a proof-of-concept for a method to simultaneously measure dose rates from neutrons and photons using a particle discriminating organic scintillation detector without the need for spectral deconvolution. The method was compared with traditional instruments and to simulation. Isotopic photon dose rates measured with this method were within 4% of simulated truth, whereas fission spectrum neutron dose rates were measured within 21%. Measurements of dose rates from both particles agree with simulated truth better than traditional instruments. This new method allows for measurement of dose equivalent from both neutrons and photons with a single instrument and no reliance on spectral deconvolution.

Angular distribution of neutron production by proton and carbon-ion therapeutic beams.

Carbon-ion beams are increasingly used in the clinical practice for external radiotherapy treatments of deep-seated tumors. At therapeutic energies, carbon ions yield significant secondary products, including neutrons, which may be of concern for the radiation protection of the patient and personnel. We simulated the neutron yield produced by proton and carbon-ion pencil beams impinging on a clinical phantom at three different angles: 15°, 45° and 90°, with respect to the beam axis. We validated the simulated results using the measured response of organic scintillation detectors. We compared the results obtained with FLUKA 2011.2 and MCNPX 2.7.0 based on three different physics models: Bertini, Isabel, and CEM. Over the different ions, energies, and angles, the FLUKA simulation results agree better with the measured data, compared to the MCNPX results. Simulations of carbon ions at low angles exhibit both the highest deviation from measured data and inter-model discrepancy, which is probably due to the different treatment of the pre-equilibrium stage. The reported neutron yield results could help in the comparison of carbon-ion and proton treatments in terms of secondary neutron production for radiation protection applications.

EVALUATION OF REPRESENTATIVENESS OF SAMPLES USED FOR INDOOR RADON SURVEYS.

The estimation of the indoor radon exposure of the population of a country is generally carried out by the means of surveys designed in order to have sample representativeness as a target (population-based survey). However, the estimates of radon concentration distributions could be affected by biases if sampling was not random or in case of differences between sample and target population characteristics. In this work, we performed a preliminary check of the representativeness of the sample used for the second Italian national survey aimed to evaluate radon concentration distribution in each Province. We found that sampled dwellings are mostly located in the main administrative centres, where average radon concentration is generally lower, as compared with the other towns of the Province. The potential source of bias identified in this work suggests to carefully control the occurrence of a sampling imbalance between 'main' cities and other cities of Province and to take it into account in data analysis.

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial.

BACKGROUND: Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS: Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patient's death or ending of the study. RESULTS: Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS: Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

Lymphocyte subsets recovery following allogeneic bone marrow transplantation (BMT): CD4+ cell count and transplant-related mortality.

To assess the kinetics of lymphocyte subset recovery, 758 allografted patients were monitored by surface markers (CD3, CD4, CD8, CD56), with a 5-year follow-up. The donor was a matched sibling donor (MSD) (n=502) or an alternative donor (family mismatched or unrelated, AD) (n=256). The stem cell source was bone marrow for all patients. CD4+ cell recovery was influenced -- in univariate analysis -- by three factors: donor type, patient age and GvHD. This was not the case for CD8+ and CD56+ cells. The median CD4+ cell count on day +35 after HSCT was 86/mul. Patients achieving this CD4+ cell count had significantly lower transplant-related mortality (TRM) compared to patients who did not achieve this CD4+ cell count (20 vs 39%, P=0.00001), due to a lower risk of lethal infections (24 vs 47%, P=0.0003). In multivariate analysis MSD (RR 3.45, P=0.0001) and recipient age less than 16 years (RR 3.23, P=0.003) were significantly associated with a better CD4+ cell recovery. CD4+ counts on day +35 was predicted TRM (RR=1.97, P=0.0017) together with acute GvHD grade II-IV (RR 1.59, P=0.0097). No difference of TRM was observed for CD8+ and CD56+ cell counts.

Spectroscopic magnetic resonance imaging of the brain: voxel localisation and tissue segmentation in the follow up of brain tumour.

The field of application of magnetic resonance spectroscopy (MRS) in biomedical research is expanding all the time and providing opportunities to investigate tissue metabolism and function. The data derived can be integrated with the information on tissue structure gained from conventional and non-conventional magnetic resonance imaging (MRI) techniques. Clinical MRS is also strongly expected to play an important role as a diagnostic tool. Essential for the future success of MRS as a clinical and research tool in biomedical sciences, both in vivo and in vitro, is the development of an accurate, biochemically relevant and physically consistent and reliable data analysis standard. Stable and well established analysis algorithms, in both the time and the frequency domain, are already available, as is free commercial software for implementing them. In this study, we propose an automatic algorithm that takes into account anatomical localisation, relative concentrations of white matter, grey matter, cerebrospinal fluid and signal abnormalities and inter-scan patient movement. The endpoint is the collection of a series of covariates that could be implemented in a multivariate analysis of covariance (MANCOVA) of the MRS data, as a tool for dealing with differences that may be ascribed to the anatomical variability of the subjects, to inaccuracies in the localisation of the voxel or slab, or to movement, rather than to the pathology under investigation. The aim was to develop an analysis procedure that can be consistently and reliably applied in the follow up of brain tumour. In this study, we demonstrate that the inclusion of such variables in the data analysis of quantitative MRS is fundamentally important (especially in view of the reduced accuracy typical of MRS measures compared to other MRI techniques), reducing the occurrence of false positives.

Search of the neutrino-less double beta decay of 82 Se into the excited states of 82 Kr with CUPID-0.

The CUPID-0 experiment searches for double beta decay using cryogenic calorimeters with double (heat and light) read-out. The detector, consisting of 24 ZnSe crystals 95 % enriched in 82 Se and two natural ZnSe crystals, started data-taking in 2017 at Laboratori Nazionali del Gran Sasso. We present the search for the neutrino-less double beta decay of 82 Se into the 0 1 + , 2 1 + and 2 2 + excited states of 82 Kr with an exposure of 5.74 kg · yr (2.24 × 10 25  emitters · yr). We found no evidence of the decays and set the most stringent limits on the widths of these processes: Γ ( 82 Se → 82 Kr 0 1 + )8.55 × 10 - 24  yr - 1 , Γ ( 82 Se → 82 Kr 2 1 + ) < 6.25 × 10 - 24  yr - 1 , Γ ( 82 Se → 82 Kr 2 2 + )8.25 × 10 - 24  yr - 1 (90 % credible interval).