The YOPP Final Summit: Assessing Past and Forecasting Future Polar Prediction Research

The successes of YOPP from the presentations and keynote presentations included * a better understanding of the impact of key polar measurements (radiosondes and space-based instruments such as microwave radiometers), and recent advancements in the current NWP observing system, achieved through coordinated OSEs in both polar regions (e.g., Sandu et al. 2021);* enhanced understanding of the linkages between Arctic and midlatitude weather (e.g., Day et al. 2019);* advancements in the atmosphere–ocean–sea ice and atmosphere–land–cryosphere coupling in NWP, and in assessing and recognizing the added value of coupling in Earth system models (e.g., Bauer et al. 2016);* deployment of tailored polar observation campaigns to address yet-unresolved polar processes (e.g., Renfrew et al. 2019);* progress in verification and forecasting techniques for sea ice, including a novel headline score (e.g., Goessling and Jung 2018);* advances in process understanding and process-based evaluation with the establishment of the YOPPsiteMIP framework and tools (Svensson 2020);* better understanding of emerging societal and stakeholder needs in the Arctic and Antarctic (e.g., Dawson et al. 2017);and * innovative transdisciplinary methodologies for coproducing salient information services for various user groups (Jeuring and Lamers 2021). The YOPP Final Summit identified a number of areas worthy of prioritized research in the area of environmental prediction and services for the polar regions: * coupled atmosphere, sea ice, and ocean models with an emphasis on advanced parameterizations and enhanced resolution at which critical phenomena start to be resolved (e.g., ocean eddies);* improved definition and representation of stable boundary layer processes, including mixed-phase clouds and aerosols;incorporation of wave–ice–ocean interactions;* radiance assimilation over sea ice, land ice, and ice sheets;understanding of linkages between polar regions and lower latitudes from a prediction perspective;* exploring the limits of predictability of the atmosphere–cryosphere–ocean system;* an examination of the observational representativeness over land, sea ice, and ocean;better representation of the hydrological cycle;and * transdisciplinary work with the social science community around the use of forecasting services and operational decision-making to name but a few. The presentations and discussions at the YOPP Final Summit identified the major legacy elements of YOPP: the YOPPsiteMIP approach to enable easy comparison of collocated multivariate model and observational outputs with the aim of enhancing process understanding, the development of an international and multi-institutional community across many disciplines investigating aspects of polar prediction and services, the YOPP Data Portal3 (https://yopp.met.no/), and the education and training delivered to early-career polar researchers. Next steps Logistical issues, the COVID-19 pandemic, but also new scientific questions (e.g., the value of targeted observations in the Southern Hemisphere), as well as technical issues emerging toward the end of the YOPP Consolidation Phase, resulted in the decision to continue the following three YOPP activities to the end of 2023: (i) YOPP Southern Hemisphere (YOPP-SH);(ii) Model Intercomparison and Improvement Project (MIIP);of which YOPPSiteMIP is a critical element;and (iii) the Societal, Economics and Research Applications (PPP-SERA) Task Team.

IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

Introduction Multisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions and how expression changes over time. In this study, we investigated expression of immune-related genes in South African MIS-C patients and controls. Methods The cohort included 30 pre-treatment MIS-C cases and 54 healthy non-inflammatory paediatric controls. Other controls included 34 patients with juvenile systemic lupus erythematosus, Kawasaki disease or other inflammatory conditions. Longitudinal post-treatment MIS-C specimens were available at various timepoints. Expression of 80 immune-related genes was determined by real-time quantitative PCR. Results A total of 29 differentially expressed genes were identified in pre-treatment MIS-C compared to healthy controls. Up-regulated genes were found to be overrepresented in innate immune pathways including interleukin-1 processing and pyroptosis. Post-treatment follow-up data were available for up to 1,200 hours after first treatment. All down-regulated genes and 17/18 up-regulated genes resolved to normal levels in the timeframe, and all patients clinically recovered. When comparing MIS-C to other febrile conditions, only IL27 expression could differentiate these two groups with high sensitivity and specificity. Conclusions These data indicate a unique 29-gene signature of MIS-C in South African children. The up-regulation of interleukin-1 and pyroptosis pathway genes highlights the role of the innate immune system in MIS-C. IL-27 is a potent anti-inflammatory and antiviral cytokine that may distinguish MIS-C from other conditions in our setting.

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.

PURPOSE: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. METHODS: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 µg/kg/day. RESULTS: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. CONCLUSION: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

Perspectives From the Foot and Ankle Department at an Academic Orthopedic Hospital During the Surge Phase of the COVID-19 Pandemic in New York City

Category: Other Introduction/Purpose: Cases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (COVID-19) first emerged in Wuhan, China, in December 2019. Since then, the virus has spread globally at a rapid pace. The first case in New York City was reported on March 1, 2020, and the World Health Organization (WHO) declared a pandemic on March 11, 2020. New York City rapidly became the epicenter of the pandemic, with hospitals across the city making a number of changes to accommodate the influx of COVID-19 patients. Here, we describe our experience in adapting to the COVID-19 pandemic as a department consisting of 10 foot and ankle fellowship-trained surgeons with up to 28 years of individual experience in an academic orthopedic hospital. Methods: Information was obtained from direct interviews with surgeons in the Foot and Ankle Service and from our institution’s intranet. Additional information was obtained by viewing twice-weekly livestreams from March 27th, 2020 to May 1st, 2020 held by the Surgeon-In-Chief, which detailed hospital-wide policies and initiatives being implemented in the wake of the COVID-19 pandemic. Results: On March 17, 2020, all elective surgeries were suspended at our institution, and a list of essential procedures was established. In-person clinical visits were limited to new patients being evaluated for essential procedures and first postoperative visits for returning patients, with all patients receiving pre-visit and on-site screening for COVID-19. All other new patient and follow-up appointments were conducted via telehealth visits. Much of our main hospital was repurposed to accept transfers of both COVID-negative and COVID-positive patients. A postanesthesia care unit and a floor of 9 operating rooms were repurposed as negative-pressure rooms for the care of critical COVID-positive patients on ventilators. An Orthopedic Triage Center (OTC) was established to relieve the patient load in the emergency departments of other hospitals in the city. Conclusion: By changing the way we delivered foot and ankle care and repurposing the roles of our employees and our institution, we have adapted strategies to continue delivering care to our patients. As we transition toward a ‘new normal,’ our goals are to gradually progress toward normal operations while keeping our patients and employees safe. With these gradual steps, we hope to emerge from this pandemic stronger and ready to adapt to the ever-changing needs of our community.