Quantifying and understanding current and future links between tropical convection and the large-scale circulation

2020 Fall.Includes bibliographical references.Tropical deep convection plays an important role in the variability of the global circulation. The Madden Julian Oscillation (MJO) is a large tropical organized convective system that propagates eastward along the equator. It is a key contributor to weather predictability at extended time scales (10-40 days). For example, variability in the MJO is linked with variability in meteorological phenomena such as landfalling atmospheric rivers, tornado and hail activity over parts of North America, and extreme temperature and rainfall patterns across the Northern Hemisphere. Links between the MJO and atmospheric variability in remote locations are heavily studied. This is in part because the current skill of weather forecasts at extended time scales is mediocre, and because of evidence suggesting that the potential predictability offered by the MJO may not be fully captured in numerical prediction models. In the first part of this dissertation, I develop a tool for these types of studies. The "Sensitivity to the Remote Influence of Periodic Events" (STRIPES) index is a novel index that condenses the information obtained through composite analysis of variables after a periodic event (such as the MJO) into a single number, which includes information about the life cycle of the event, and for a range of lags with respect to each stage of the event. I apply the STRIPES index to surface observations and show that the MJO signal is detectable and significant at the level of individual weather stations over many parts of North America, and that the maximum strength of this signal exhibits regionality and seasonality. Tropical convection affects the extratropics primarily through the excitation of Rossby waves at the places where the upper-tropospheric divergent outflow associated with deep convection interacts with the background wind. In a future warmer climate, the strength of the mean circulation and convective mass flux is expected to weaken. A potential consequence is a weakening of Rossby wave excitation by tropical convective systems such as the MJO. In the second part of this study, I analyze a set of idealized simulations with specified surface warming and superparameterized convection and develop a framework to better understand why the mean circulation weakens with warming. I show that the decrease in the strength of the mean circulation can be explained by the slow rate at which atmospheric radiative cooling intensifies relative to the comparatively fast rate that the tropical dry static stability increases. I also show that despite a decrease in the mean convective mass flux, the warming tendency of the convective mass flux over the most deeply- convecting regions is not constrained to follow that of the global mean. In the final part of this dissertation, I consider how changes in the MJO and of the mean atmospheric state due to warming from increases in greenhouse gas concentrations may lead to changes in the MJO's impact over the North Pacific and North America. Specifically, I show that changes to the atmosphere's mean state dry static energy and winds have a larger impact on the MJO teleconnection than changes to MJO intensity and propagation characteristics

Understanding and Visualizing Droplet Distributions in Simulations of Shallow Clouds

Thorough analysis of local droplet-level interactions is crucial to better understand the microphysical processes in clouds and their effect on the global climate. High-accuracy simulations of relevant droplet size distributions from Large Eddy Simulations (LES) of bin microphysics challenge current analysis techniques due to their high dimensionality involving three spatial dimensions, time, and a continuous range of droplet sizes. Utilizing the compact latent representations from Variational Autoencoders (VAEs), we produce novel and intuitive visualizations for the organization of droplet sizes and their evolution over time beyond what is possible with clustering techniques. This greatly improves interpretation and allows us to examine aerosol-cloud interactions by contrasting simulations with different aerosol concentrations. We find that the evolution of the droplet spectrum is similar across aerosol levels but occurs at different paces. This similarity suggests that precipitation initiation processes are alike despite variations in onset times.Comment: 4 pages, 3 figures, accepted at NeurIPS 2023 (Machine Learning and the Physical Sciences Workshop

Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis

Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee

Objective: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. Material and methods: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted. Results: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1–1.2) (all ADC expressed in * 10−3 mm2/s), versus 1.6 (1.5–1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7–0.9) at diagnosis and 1.1 (1.0–1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3–0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6–3.2]) between the mean ADC change and event-free survival. Conclusion: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients. Graphical Abstract: [Figure not available: see fulltext.

ClimSim: A large multi-scale dataset for hybrid physics-ML climate emulation

Modern climate projections lack adequate spatial and temporal resolution due to computational constraints. A consequence is inaccurate and imprecise predictions of critical processes such as storms. Hybrid methods that combine physics with machine learning (ML) have introduced a new generation of higher fidelity climate simulators that can sidestep Moore's Law by outsourcing compute-hungry, short, high-resolution simulations to ML emulators. However, this hybrid ML-physics simulation approach requires domain-specific treatment and has been inaccessible to ML experts because of lack of training data and relevant, easy-to-use workflows. We present ClimSim, the largest-ever dataset designed for hybrid ML-physics research. It comprises multi-scale climate simulations, developed by a consortium of climate scientists and ML researchers. It consists of 5.7 billion pairs of multivariate input and output vectors that isolate the influence of locally-nested, high-resolution, high-fidelity physics on a host climate simulator's macro-scale physical state.The dataset is global in coverage, spans multiple years at high sampling frequency, and is designed such that resulting emulators are compatible with downstream coupling into operational climate simulators. We implement a range of deterministic and stochastic regression baselines to highlight the ML challenges and their scoring. The data (https://huggingface.co/datasets/LEAP/ClimSim_high-res) and code (https://leap-stc.github.io/ClimSim) are released openly to support the development of hybrid ML-physics and high-fidelity climate simulations for the benefit of science and society

Time to broaden the eligibility criteria in pediatric oncology trials? An analysis of patients with rhabdomyosarcoma non-eligible to the EpSSG RMS2005 trial

Purpose Clinical trials include a series of eligibility and exclusion criteria that define the study population to reduce inter-patient heterogeneity and increase safety. Little is known about children with oncological diseases excluded from trials because they do not satisfy these criteria. We analysed the eligibility criteria adopted in the European paediatric Soft tissue sarcoma Study Group RMS2005 study and the survival of non-eligible patients. Patients and Methods RMS2005 run from 10/2005 to 12/2016. Eligibility criteria were age ≤25 years; pathologically proven diagnosis of rhabdomyosarcoma (RMS); no evidence of metastases; no pre-treatment; no pre-existing conditions preventing treatment; no previous malignant tumours and an interval between diagnostic surgery and the start of treatment ≤8 weeks. Clinical characteristics, 5-year progression-free survival (PFS), and overall survival (OS) were analysed for eligible and non-eligible patients. Results The 79 non-eligible patients (4.3% of registered patients) were older than eligible patients (p&lt;0.0001), with RMS arising in favourable sites (p=0.004) and completely resected at diagnosis (p&lt;0.0001). PFS for non-eligible vs. eligible patients was 67.1% (95%CI 55.3-76.5) vs. 71.5% Journal Pre-proof (95%CI 69.3-73.6) (p=0.23) and OS 77.1% (95%CI 65.7-85.1) vs. 80.4% (95%CI 78.4-82.3) (p=0.12), respectively. Patients with a delayed start of treatment or pre-treated had significantly better PFS than those with a pre-existing condition (p=0.0004). Conclusion: non-eligible patients data should be systematically collected. This will be important to confirm that trial eligibility criteria for patients with RMS could be modified without jeopardizing results and increasing study enrolment and generalizability of results

Advances in the prediction of MJO-Teleconnections in the S2S forecast systems

This study evaluates the ability of state-of-the-art subseasonal to seasonal (S2S) forecasting systems to represent and predict the teleconnections of the Madden Julian Oscillations and their effects on weather in terms of midlatitude weather patterns and North Atlantic tropical cyclones. This evaluation of forecast systems applies novel diagnostics developed to track teleconnections along their preferred pathways in the troposphere and stratosphere, and to measure the global and regional responses induced by teleconnections across both the Northern and Southern Hemispheres. Results of this study will help the modeling community understand to what extent the potential to predict the weather on S2S time scales is achieved by the current generation of forecasting systems, while informing where to focus further development efforts. The findings of this study will also provide impact modelers and decision makers with a better understanding of the potential of S2S predictions related to MJO teleconnections.ISSN:0003-0007ISSN:1520-047

Access to clinical trials for adolescents with soft tissue sarcomas: Enrollment in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols

Adolescents with cancer are enrolled in clinical trials at far lower rates than children. This report compares the number of adolescents (15-19-year-olds) and children (0-14-year-olds) enrolled in the protocols of the European pediatric Soft tissue sarcoma Study Group (EpSSG) with the number of cases expected to occur. The observed-to-expected (O/E) ratio was detected in the EpSSG countries contributing most of the cases, that is, Italy, France, Spain, the Netherlands, United Kingdom, and Ireland. The observed cases included patients enrolled in any of the EpSSG protocols from October 2008 to October 2015, when all EpSSG protocols were open in these countries. The number of expected cases was calculated from the incidence rates estimated throughout the RARECAREnet database in the countries' population-based cancer registries. In the countries considered, 2,118 cases aged 0-19 years were enrolled in the EpSSG trials from 2008 to 2015: 82.8% were children and 17.2% were adolescents. The O/E ratio was 0.30 among patients 15-19 years old, as opposed to 0.64 for those 0-14 years old. The O/E ratio differed for the different subtypes: in adolescents, it was 0.64 and 0.18 for rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), respectively; in children, it was 0.77 and 0.50, respectively. The O/E ratios differed across the countries considered. Adolescents were less well represented than children on the EpSSG protocols, with better enrolment for RMS than for NRSTS for all age group

Shedding a Light on the Challenges of Adolescents and Young Adults with Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database

Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience

Background: Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. Material and methods: Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. Results: A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0). Conclusions: Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects. (C) 2016 Elsevier Ltd. All rights reserved