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BackgroundThe endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic adjuvant treatment strategies for women with endometrial cancer.Primary Objective(s)The RAINBO program of clinical trials will investigate four molecular class-directed adjuvant treatment strategies following surgical resection to either increase cure rates through the addition of novel targeted therapies or safely reduce toxicity and improve quality of life through treatment de-escalation.Study HypothesisMolecular-directed adjuvant treatment strategies will improve clinical outcomes and reduce toxicity of unwarranted therapies in women with endometrial cancer. The overarching and translational research RAINBO program will advance knowledge of predictive and prognostic (bio)markers that will improve prognostication and treatment allocation.Trial DesignThe RAINBO program is a platform of four international clinical trials and an overarching research program. The randomized phase III p53abn-RED trial for women with invasive stage I–III p53abn endometrial cancer compares adjuvant chemoradiation followed by olaparib for 2 years with adjuvant chemoradiation alone. The randomized phase III MMRd-GREEN trial for women with stage II (with lymphovascular space invasion (LVSI)) or stage III mismatch repair-deficient (MMRd) endometrial cancer compares adjuvant radiotherapy with concurrent and adjuvant durvalumab for 1 year to radiotherapy alone. The randomized phase III NSMP-ORANGE trial is a treatment de-escalation trial for women with estrogen receptor positive stage II (with LVSI) or stage III no specific molecular profile (NSMP) endometrial cancer comparing radiotherapy followed by progestin for 2 years to adjuvant chemoradiation. ThePOLEmut-BLUE trial is a phase II trial in which the safety of de-escalation of adjuvant therapy is investigated for women with stage I–IIIPOLEmut endometrial cancer: no adjuvant therapy for lower-risk disease and no adjuvant therapy or radiotherapy alone for higher-risk disease. The overarching RAINBO program will combine data and tumor material of all participants to perform translational research and evaluate molecular class-based adjuvant therapy in terms of efficacy, toxicity, quality of life, and cost-utility.Major Inclusion/Exclusion CriteriaInclusion criteria include a histologically confirmed diagnosis of endometrial cancer treated by hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel lymph node biopsy, with no macroscopic residual disease after surgery and no distant metastases, and molecular classification according to the WHO 2020 algorithm.Primary Endpoint(s)Recurrence-free survival at 3 years in the p53abn-RED, MMRd-GREEN, and NSMP-ORANGE trials and pelvic recurrence at 3 years in thePOLEmut-BLUE trial.Sample SizeThe p53abn-RED trial will include 554 patients, the MMRd-GREEN trial 316, the NSMP-ORANGE trial 600, and thePOLEmut-BLUE trial 145 (120 for lower-risk disease and approximately 25 for higher-risk disease). The overarching research program will pool the four sub-trials resulting in a total sample size of around 1600.Estimated Dates for Completing Accrual and Presenting ResultsThe four clinical trials will have different completion dates; main results are expected from 2028.Trial Registration NumberThe RAINBO program is registered at clinicaltrials.gov (NCT05255653).

To assess climate change effects, it is important to understand how the water cycle interacts with other Earth system processes. Redistributions of environmental masses - atmosphere, ocean, continental hydrology - induce detectable variations in the Earth's gravity field and crustal deformations, known as loading effects. The GNSS (Global Navigation Satellite System) and GRACE (Gravity Recovery And Climate Experiment) and GRACE Follow-On space gravity missions allow monitoring water mass transfers giving long time series (> 20 years) highly complementary in terms of both spatial and temporal resolutions. South America, with its large hydrological basins, has the strongest seasonal hydrological signal in the world. The hydrological loading signal exhibits different spectral contributions resulting from the superposition of different phenomena acting at different scales. It contains several markers of climate change including changes in precipitation, water storage and extreme events. However, climate markers are not directly accessible in the signals observed by space geodesy. Reliable extraction of the hydrological part therefore requires the use of efficient signal processing method to separate the different contributions of mass redistribution and to compare the observations with the deformations predicted by geodynamical models. We apply an innovative multivariate analysis method combining MSSA (Multi-Channel Singular Spectrum Analysis) and MICA (Multidimensional Independent Component Analysis) to permanent GNSS sites in South America. We demonstrate how better inferring hydrological loading signal contributes to a better understanding of the water cycle, enhancing global inference of the mass transport at the Earth’s surface and gives significant insights on climate change driven signals., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

PPP-RTK (Precise Point Positioning - Real Time Kinematic) is consistently emerging as an alternative to provide centimeter level accuracy for real-time GNSS (Global Navigation Satellite Systems) positioning. This method is based on the Space State Representation (SSR) concept, which requires that errors affecting GNSS observables be either corrected or estimated in GNSS data processing. The parameters estimation is usually ensured by the application of the S-system theory. It has been shown that introducing atmospheric SSR corrections as a priori information to PPP-RTK users can significantly improve their results. PPP-RTK is especially useful in regions where only GNSS active reference stations with a sparse spatial distribution are available to users, such as South America. This region faces several challenges in GNSS positioning performance due to ionospheric disturbances, so providing high-quality ionospheric delay SSR corrections to PPP-RTK is crucial for enhancing GNSS applications there. Most PPP-RTK studies focus on geographic regions with low ionospheric activity. This contribution assesses an alternative for generating and applying SSR ionospheric corrections for simulated PPP-RTK users in regions affected by high levels of ionospheric activity. The proposed approach involves using adaptive constraints for ionospheric SSR corrections and ensuring consistency with the recommended International GNSS Service (IGS) standards for broadcasting SSR corrections to users. Preliminary results show that this approach can reduce the time required for PPP-RTK to achieve 10 centimeters horizontal accuracy by approximately 42%., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

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