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Medulloblastoma (MB), the most common form of pediatric brain malignancy, has a low frequency of oncogenic mutations but pronouncedly abnormal DNA methylation changes. Epigenetic analysis of circulating cell-free tumor DNA (ctDNA) by liquid biopsy offers an approach for real-time monitoring of tumor status without tumor dissection. In this study, we identified 6598 differentially methylated CpGs in both MB tumors and the ctDNA isolated from matched cerebrospinal fluid (CSF) compared with normal cerebellum, which could be used to detect MB tumor occurrence and determine its subtype. Furthermore, DNA methylation changes in serial CSF samples could be used to monitor the treatment response and tumor recurrence. Integrating our data with large public datasets, we identified reliable MB DNA methylation signatures in ctDNA that have potential diagnostic and prognostic values. Our study sets the stage for exploiting epigenetic markers in CSF to improve the clinical management of patients with MB.The Southern Ocean plays a crucial role in regulating atmospheric CO2 on centennial to millennial time scales. However, observations of sufficient resolution to explore this have been lacking. Here, we report high-resolution, multiproxy records based on precisely dated deep-sea corals from the Southern Ocean. Paired deep (∆14C and δ11B) and surface (δ15N) proxy data point to enhanced upwelling coupled with reduced efficiency of the biological pump at 14.6 and 11.7 thousand years (ka) ago, which would have facilitated rapid carbon release to the atmosphere. Transient periods of unusually well-ventilated waters in the deep Southern Ocean occurred at 16.3 and 12.8 ka ago. Contemporaneous atmospheric carbon records indicate that these Southern Ocean ventilation events are also important in releasing respired carbon from the deep ocean to the atmosphere. Our results thus highlight two distinct modes of Southern Ocean circulation and biogeochemistry associated with centennial-scale atmospheric CO2 jumps during the last deglaciation.Madagascar and the Mascarene Islands of Mauritius and Rodrigues underwent catastrophic ecological and landscape transformations, which virtually eliminated their entire endemic vertebrate megafauna during the past millennium. These ecosystem changes have been alternately attributed to either human activities, climate change, or both, but parsing their relative importance, particularly in the case of Madagascar, has proven difficult. Here, we present a multimillennial (approximately the past 8000 years) reconstruction of the southwest Indian Ocean hydroclimate variability using speleothems from the island of Rodrigues, located ∼1600 km east of Madagascar. The record shows a recurring pattern of hydroclimate variability characterized by submillennial-scale drying trends, which were punctuated by decadal-to-multidecadal megadroughts, including during the late Holocene. Our data imply that the megafauna of the Mascarenes and Madagascar were resilient, enduring repeated past episodes of severe climate stress, but collapsed when a major increase in human activity occurred in the context of a prominent drying trend.Harsh exclusionary discipline predicts major negative life outcomes, including adult incarceration and unemployment. This breeds racial inequality because Black students are disproportionately at risk for this type of discipline. Can a combination of policy and psychological interventions reduce this kind of discipline and mitigate this inequality? Two preregistered experiments (Nexperiment1 = 246 teachers; Nexperiment2 = 243 teachers) used an established paradigm to systematically test integration of two and then three policy and psychological interventions to mitigate the consequences of bias (troublemaker labeling and pattern perception) on discipline (discipline severity). Results indicate that the integrated interventions can curb teachers' troublemaker labeling and pattern prediction toward Black students who misbehave in a hypothetical paradigm. In turn, integration of the three components reduced racial inequality in teachers' discipline decisions. This research informs scientific theory, public policy, and interventions.It is well known that an increased viscosity slows down fluid dynamics. https://www.selleckchem.com/products/Decitabine.html Here we show that this intuitive rule is not general and can fail for liquids flowing in confined liquid-repellent systems. A gravity-driven, highly viscous glycerol droplet inside a sealed superhydrophobic capillary is moving more than 10 times faster than a water droplet with three-orders-of-magnitude lower viscosity. Using tracer particles, we show that the low-viscosity droplets are rapidly rotating internally, with flow velocities greatly exceeding the center-of-mass velocity. This is in stark contrast to the faster moving high-viscosity droplets with nearly vanishing internal flows. The anomalous viscosity-enhanced flow is caused by a viscosity-suppressed deformation of the droplet-air interface and a hydro- and aerodynamic coupling between the droplet and the air trapped within the micro/nanostructures (plastron). Our work demonstrates the unexpected role of the plastron in controlling fluid flow beyond the mere reduction in contact area and friction. Unintentional injuries in children under the age of 5 years commonly occur in the home and disproportionately affect those living in disadvantaged circumstances. Targeted home safety promotion should be offered to families most at risk but there is a paucity of standardised evidence-based resources available for use across family-support practitioners. To assess the effectiveness, implementation and cost-effectiveness of a 2-year home safety programme (Stay One Step Ahead) developed by parents, practitioners and researchers, and delivered by a range of family support providers in inner-city localities, compared with usual care in matched control localities. Parents of children aged 0 to 7 months will be recruited to a controlled before and after observational study. The primary outcome is home safety assessed by the proportion of families with a fitted and working smoke alarm, safety gate on stairs (where applicable) and poisons stored out of reach, assessed using parent-administered questionnaires at baseline, 12 and 24 months.
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