Indirect evaluation of Mars Gravity Model 2011 using a replication experiment on Earth

Curtin University’s Mars Gravity Model 2011 (MGM2011) is a high-resolution composite set of gravity field functionals that uses topography-implied gravity effects at medium- and short-scales (~125 km to ~3 km) to augment the space-collected MRO110B2 gravity model. Ground-truth gravity observations that could be used for direct validation of MGM2011 are not available on Mars’s surface. To indirectly evaluate MGM2011 and its modelling principles, an as-close-as-possible replication of the MGM2011 modelling approach was performed on Earth as the planetary body with most detailed gravity field knowledge available. Comparisons among six ground-truth data sets (gravity disturbances, quasigeoid undulations and vertical deflections) and the MGM2011-replication over Europe and North America show unanimously that topography-implied gravity information improves upon space-collected gravity models over areas with rugged terrain. The improvements are ~55% and ~67% for gravity disturbances, ~12% and ~47% for quasigeoid undulations, and ~30% to ~50% for vertical deflections. Given that the correlation between space-collected gravity and topography is higher for Mars than Earth at spatial scales of a few 100 km, topography-implied gravity effects are more dominant on Mars. It is therefore reasonable to infer that the MGM2011 modelling approach is suitable, offering an improvement over space-collected Martian gravity field models

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population

Risk factors for arterial ischaemic stroke in children include vasculopathy and prothrombotic risk factors but their relative importance to recurrent stroke is uncertain. Data on recurrent stroke from the databases held in Canada (Toronto), Germany (Kiel-Lubeck/Munster), and UK (London/Southampton) were pooled. Data were available from 894 patients aged 1 month to 18 years at first stroke (median age 6 years) with a median follow-up of 35 months. 160/894 patients (17.9%) had recurrence from 1 day to 136 months after first stroke (median 3.1 months). Among 288 children with vasculopathy, recurrence was significantly more common (hazard ratio (HR) 2.5, 95% confidence intervals (CI) 1.92-3.5) compared to children without vasculopathy. Adjusting for vasculopathy, isolated antithrombin deficiency (HR 3.9; 95%CI 1.4-10.9), isolated elevated lipoprotein (a) (HR 2.3; 95%CI 1.3-4.1), and the presence of more than one prothrombotic risk (HR 1.9; 95%CI 1.12-3.2) were independently associated with an increased risk of recurrence. Recurrence rates calculated per 100 person-years were 10 (95%CI 3-24) for antithrombin deficiency, 6 (95%CI 4-9) for elevated lipoprotein (a), and 13 (95%CI 7-20) for the presence of more than one prothrombotic risk. Identifying children at increased for second stroke events is important in intensifying measures aimed at preventing recurrent stroke

Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children: a Randomised, Controlled, Phase 3 Trial

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11–1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51–6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding: Bayer AG and Janssen Research & Development. © 2020 Elsevier Ltd