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Background: We examined the association between intellectual disabilities (ID) and pneumonia severity at admission. Methods: We extracted patients admitted to hospital for pneumonia from July 2010 to March 2018 using the Diagnosis Procedure Combination database. We measured pneumonia severity using the A-DROP system. After 1:4 cohort matching between patients with and without ID, we conducted conditional logistic regression and mediation analyses. Results: Of 1,141,158 patients, 531 had ID, and they had more severe pneumonia at admission (24.5% vs. 9.5%; P < 0.001). ID was significantly associated with severe pneumonia at admission (OR = 3.50; 95% CI: 2.68-4.58) and activities of daily living (ADL) mediated 73.8% (95% CI: 50.9%-105.0%) of the total association. Conclusions: Social barriers caused by reduced ADL may prevent patients with ID from accessing health care before their pneumonia becomes severe. Removing these barriers may decrease mortality from pneumonia among patients with ID by improving health care access.

Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [211At]PSMA-5 was administered to both normal male ICR mice (n = 85) and cynomolgus monkeys (n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day (n = 10 per group) and 14 days (n = 5 per group). Monkeys were observed 24 h post-administration of [211At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [211At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211At using a cyclotron supports its applicability for clinical use. [ABSTRACT FROM AUTHOR]

The effects of external forcing variation on the intrinsic variability in the upper-layer circulation occurring within the East Sea (Sea of Japan) and its physical mechanism are analyzed using numerical experiments. In this study, the experiments were conducted with climatological annual/monthly mean forcings (constant/seasonal forcings). The intrinsic variability is mainly distributed in the meandering regions around the main current path with the comparatively large variability limited to the southern region. The reason of greater intrinsic variability mainly in the southern part of the East Sea than in the northern part is that more energy is required from external forcings to change the thicker upper layer formed in the northern part due to seasonal forcings (strong wind stress and surface heat flux). Although the experiments show slight differences, westward propagation of the Rossby wave appears in areas where the variability is large. The transport of the eddy momentum flux associated with the Rossby wave modulates the strength of the eastward jet and the north–south shift of its axis. Among the external forcings, the volume transport through the Korea/Tsushima Strait is the most important driver of intrinsic variability, and wind stress plays an important role in expanding and strengthening intrinsic variability. Significance Statement: Intrinsic variability is an important factor in understanding the total variability in the upper-layer circulation in the East Sea (Sea of Japan). However, the physical mechanisms of intrinsic variability remain unclear. This study investigates the physical mechanisms of intrinsic variability occurring within the East Sea. The intrinsic variability occurs mainly around the main current path, especially the meandering current. Based on numerical experiments, the mechanism of the intrinsic variability is represented by the fluctuation in the strength of the eastward current or the north–south movement of its axis caused by the Rossby wave. [ABSTRACT FROM AUTHOR]