Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Damping signatures at JUNO, a medium-baseline reactor neutrino oscillation experiment

We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, nu(3) decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on tau(3)/m(3) in the nu(3) decay model, the width of the neutrino wave packet sigma(x), and the intrinsic relative dispersion of neutrino momentum sigma(rel)

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Model-independent Approach of the JUNO 8B Solar Neutrino Program

The physics potential of detecting 8B solar neutrinos will be exploited at the Jiangmen Underground Neutrino Observatory (JUNO), in a model-independent manner by using three distinct channels of the charged current (CC), neutral current (NC), and elastic scattering (ES) interactions. Due to the largest-ever mass of 13C nuclei in the liquid scintillator detectors and the expected low background level, 8B solar neutrinos are observable in the CC and NC interactions on 13C for the first time. By virtue of optimized event selections and muon veto strategies, backgrounds from the accidental coincidence, muon-induced isotopes, and external backgrounds can be greatly suppressed. Excellent signal-to-background ratios can be achieved in the CC, NC, and ES channels to guarantee the observation of the 8B solar neutrinos. From the sensitivity studies performed in this work, we show that JUNO, with 10 yr of data, can reach the 1σ precision levels of 5%, 8%, and 20% for the 8B neutrino flux, sin 2 θ 12 , and Δ m 21 2 , respectively. Probing the details of both solar physics and neutrino physics would be unique and helpful. In addition, when combined with the Sudbury Neutrino Observatory measurement, the world's best precision of 3% is expected for the measurement of the 8B neutrino flux

JUNO physics and detector

The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kton liquid scintillator detector in a laboratory at 700-m underground. An excellent energy resolution and a large fiducial volume offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. With six years of data, the neutrino mass ordering can be determined at a 3-4 sigma significance and the neutrino oscillation parameters sin(2 )theta(12), Delta m(21)(2), and vertical bar Delta m(32)(2)vertical bar can be measured to a precision of 0.6% or better, by detecting reactor antineutrinos from the Taishan and Yangjiang nuclear power plants. With ten years of data, neutrinos from all past core-collapse supernovae could be observed at a 3 sigma significance; a lower limit of the proton lifetime, 8.34 x 10(33) years (90% C.L.), can be set by searching for p -> (nu) over barK(+); detection of solar neutrinos would shed new light on the solar metallicity problem and examine the vacuum-matter transition region. A typical core-collapse supernova at a distance of 10 kpc would lead to similar to 5000 inverse-beta-decay events and similar to 2000 (300) all-flavor neutrino-proton (electron) elastic scattering events in JUNO. Geo-neutrinos can be detected with a rate of similar to 400 events per year. Construction of the detector is very challenging. In this review, we summarize the final design of the JUNO detector and the key R&D achievements, following the Conceptual Design Report in 2015 (Djurcic et al., 2015). All 20-inch PMTS have been procured and tested. The average photon detection efficiency is 28.9% for the 15,000 MCP PMTS and 28.1% for the 5000 dynode PMTS, higher than the JUNO requirement of 27%. Together with the >20 m attenuation length of the liquid scintillator achieved in a 20-ton pilot purification test and the >96% transparency of the acrylic panel, we expect a yield of 1345 photoelectrons per MeV and an effective relative energy resolution of 3.02%/root E(MeV) in simulations (Abusleme et al., 2021). To maintain the high performance, the underwater electronics is designed to have a loss rate <0.5% in six years. With degassing membranes and a micro-bubble system, the radon concentration in the 35 kton water pool could be lowered to <10 mBq/m(3). Acrylic panels of radiopurity <0.5 ppt U/Th for the 35.4-m diameter liquid scintillator vessel are produced with a dedicated production line. The 20 kton liquid scintillator will be purified onsite with Alumina filtration, distillation, water extraction, and gas stripping. Together with other low background handling, singles in the fiducial volume can be controlled to similar to 10 Hz. The JUNO experiment also features a double calorimeter system with 25,600 3-inch PMTS, a liquid scintillator testing facility OSIRIS, and a near detector TAO. (JUNO Collaboration

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

JUNO Sensitivity to Invisible Decay Modes of Neutrons

We explore the bound neutrons decay into invisible particles (e.g., $n\rightarrow 3 \nu$ or $nn \rightarrow 2 \nu$) in the JUNO liquid scintillator detector. The invisible decay includes two decay modes: $n \rightarrow { inv}$ and $nn \rightarrow { inv}$. The invisible decays of $s$-shell neutrons in $^{12}{\rm C}$ will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $\bar{\nu}_e$, natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $\tau/B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, {\rm yr}$ and $\tau/B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, {\rm yr}$.Comment: 28 pages, 7 figures, 4 table

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362