Precompetitive consensus building to facilitate the use of digital health technologies to support Parkinson Disease drug development through regulatory science

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson’s Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies

Search for astrophysical electron antineutrinos in Super-Kamiokande with 0.01wt% gadolinium-loaded water

We report the first search result for the flux of astrophysical electron antineutrinos for energies O(10) MeV in the gadolinium-loaded Super-Kamiokande (SK) detector. In June 2020, gadolinium was introduced to the ultra-pure water of the SK detector in order to detect neutrons more efficiently. In this new experimental phase, SK-Gd, we can search for electron antineutrinos via inverse beta decay with efficient background rejection and higher signal efficiency thanks to the high efficiency of the neutron tagging technique. In this paper, we report the result for the initial stage of SK-Gd with a $22.5\times552$ $\rm kton\cdot day$ exposure at 0.01% Gd mass concentration. No significant excess over the expected background in the observed events is found for the neutrino energies below 31.3 MeV. Thus, the flux upper limits are placed at the 90% confidence level. The limits and sensitivities are already comparable with the previous SK result with pure-water ($22.5 \times 2970 \rm kton\cdot day$) owing to the enhanced neutron tagging

Performance of SK-Gd's upgraded real-time supernova monitoring system

Among multi-messenger observations of the next galactic core-collapse supernova, Super-Kamiokande (SK) plays a critical role in detecting the emitted supernova neutrinos, determining the direction to the supernova (SN), and notifying the astronomical community of these observations in advance of the optical signal. On 2022, SK has increased the gadolinium dissolved in its water target (SK-Gd) and has achieved a Gd concentration of 0.033%, resulting in enhanced neutron detection capability, which in turn enables more accurate determination of the supernova direction. Accordingly, SK-Gd's real-time supernova monitoring system (Abe te al. 2016b) has been upgraded. SK_SN Notice, a warning system that works together with this monitoring system, was released on December 13, 2021, and is available through GCN Notices (Barthelmy et al. 2000). When the monitoring system detects an SN-like burst of events, SK_SN Notice will automatically distribute an alarm with the reconstructed direction to the supernova candidate within a few minutes. In this paper, we present a systematic study of SK-Gd's response to a simulated galactic SN. Assuming a supernova situated at 10 kpc, neutrino fluxes from six supernova models are used to characterize SK-Gd's pointing accuracy using the same tools as the online monitoring system. The pointing accuracy is found to vary from 3-7∘ depending on the models. However, if the supernova is closer than 10 kpc, SK_SN Notice can issue an alarm with three-degree accuracy, which will benefit follow-up observations by optical telescopes with large fields of view

Measurements of the charge ratio and polarization of cosmic-ray muons with the Super-Kamiokande detector

We present the results of the charge ratio (R) and polarization (Pμ0) measurements using the decay electron events collected from 2008 September to 2022 June by the Super-Kamiokande detector. Because of its underground location and long operation, we performed high precision measurements by accumulating cosmic-ray muons. We measured the muon charge ratio to be R=1.32±0.02 (stat.+syst.) at EμcosθZenith=0.7+0.3−0.2 TeV, where Eμ is the muon energy and θZenith is the zenith angle of incoming cosmic-ray muons. This result is consistent with the Honda flux model while this suggests a tension with the πK model of 1.9σ. We also measured the muon polarization at the production location to be Pμ0=0.52±0.02 (stat.+syst.) at the muon momentum of 0.9+0.6−0.1 TeV/c at the surface of the mountain; this also suggests a tension with the Honda flux model of 1.5σ. This is the most precise measurement ever to experimentally determine the cosmic-ray muon polarization near 1 TeV/c. These measurement results are useful to improve the atmospheric neutrino simulations

ADA package specifications, path expressions and monitors

SIGLELD:7056.15(DOC--81/25). / BLDSC - British Library Document Supply CentreGBUnited Kingdo