Working from home during the COVID-19 pandemic: surveys of the Society for Pediatric Radiology and the Society of Chiefs of Radiology at Children's Hospitals.

BACKGROUND: Due to the COVID-19 pandemic, some pediatric radiologists have shifted to working from home; the long-term ramifications for pediatric radiologists and departments have not yet been defined. OBJECTIVE: To characterize experiences of working from home associated with the COVID-19 pandemic and guide expectations after the pandemic is controlled, via separate surveys of Society for Pediatric Radiology (SPR) and Society of Chiefs of Radiology at Children's Hospitals (SCORCH) members. MATERIALS AND METHODS: Two separate surveys were conducted. In the first, SPR members were surveyed Jan. 11 through Feb. 8, 2021. The response rate was 17.0% (255 of 1,501). Survey questions included demographics, information on the ability to work from home and subjective experiences ranked on a scale of 0 to 10. The survey enabled segregation and comparison of responses between those with and without home PACS. In the second survey, SCORCH members were surveyed Dec. 8, 2020, through Jan. 8, 2021. The response rate was 51.5% (51/99). Survey questions included the logistics of working from home, technical specifications and the expectations on clinical duties performed from home. The Wilcoxon rank test was used to determine statistical significance of compared variables between respondents with and without home PACS in SPR members, and expectations between SPR and SCORCH members. Descriptive statistics summarized demographic questions and free text responses. RESULTS: The majority of member respondents (81.2%, 207/255) had a home PACS and most departments provided home PACS to faculty (94.1%, 48/51). Overall, radiologists who could work from home were satisfied with their ability to work from home (mean rating: 8.3/10) and were significantly more satisfied than predicted by those without home PACS (5.9/10, P<0.0001). Respondents overwhelmingly indicated they were less able to teach trainees (mean rating: 2.7/10) and had decreased emotional engagement (mean rating: 4.4/10), but had improved research productivity and cognitive ability for research when working from home (mean rating for both: 5.3/10). Regarding the expectations of the ability to work from home after no longer needing to address the pandemic, department chairs generally favored fewer rotations from home, with 97.9% (47/48) indicating working from home should be 60% or fewer assignments, compared with 84.1% (164/195) of individual radiologists (P=0.071). CONCLUSIONS: Due to the COVID-19 pandemic, there has been a shift to working from home using PACS. Results of these SPR and SCORCH member surveys can help inform future decisions regarding pediatric radiologists working from home once the pandemic has been controlled.

The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase.

γ-secretase is responsible for the proteolysis of amyloid precursor protein (APP) into short, aggregation-prone amyloid-beta (Aß) peptides, which are centrally implicated in the pathogenesis of Alzheimer's disease (AD). Despite considerable interest in developing γ-secretase targeting therapeutics for the treatment of AD, the precise mechanism by which γ-secretase produces Aß has remained elusive. Herein, we demonstrate that γ-secretase catalysis is driven by the stabilization of an enzyme-substrate scission complex via three distinct amino-acid-binding pockets in the enzyme's active site, providing the mechanism by which γ-secretase preferentially cleaves APP in three amino acid increments. Substrate occupancy of these three pockets occurs after initial substrate binding but precedes catalysis, suggesting a conformational change in substrate may be required for cleavage. We uncover and exploit substrate cleavage preferences dictated by these three pockets to investigate the mechanism by which familial Alzheimer's disease mutations within APP increase the production of pathogenic Aß species.