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Large earthquakes are usually assumed to release all of the strain accumulated since the previous event, implying a reduced seismic hazard after them. However, long records of seismic history at several subduction zones suggest supercycle behaviour, where centuries-long accumulated strain is released through clustered large earthquakes, resulting in an extended period of enhanced seismic hazard. Here we combine historical seismology results, present-day geodesy data, and dense local observations of the recent M w 7.8 2016 Pedernales earthquake to reconstruct the strain budget at the Ecuador subduction zone since the great 1906 earthquake. We show that the Pedernales earthquake involved the successive rupture of two patches on the plate interface that were locked prior to the earthquake and most probably overlaps the area already ruptured in 1942 by a similar earthquake. However, we find that coseismic slip in 2016 exceeds the deficit accumulated since 1942. The seismic moment of every large earthquake during the twentieth century further exceeds the moment deficit accumulated since 1906. These results, together with the seismic quiescence before 1906 highlighted by historical records and marine palaeoseismology, argue for an earthquake supercycle at the Ecuador–Colombia margin. This behaviour, which has led to an enhanced seismic hazard for 110 years, is possibly still going on and may apply to other subduction zones that recently experienced a great earthquake. Large earthquakes are often assumed to reset the seismic hazard of a region. Analysis of recent and historical seismicity in Ecuador suggests that this region may experience clusters of large earthquakes and extended periods of high seismic hazard.

Regions of intense continental deformation, termed continental slivers, have been identified in Chile, Bolivia and Ecuador. Analyses of GPS data now identify another large sliver in Peru, the Inca Sliver, that is moving away from a neighbouring sliver in Ecuador—implying that moving continental slivers control the deformation of almost the entire Andean mountain range. Along the western margin of South America, plate convergence is accommodated by slip on the subduction interface and deformation of the overriding continent 1 , 2 , 3 , 4 , 5 , 6 . In Chile 1 , 2 , 3 , 4 , Bolivia 6 , Ecuador and Colombia 5 , 7 , continental deformation occurs mostly through the motion of discrete domains, hundreds to thousands of kilometres in scale. These continental slivers are wedged between the Nazca and stable South American plates. Here we use geodetic data to identify another large continental sliver in Peru that is about 300–400 km wide and 1,500 km long, which we call the Inca Sliver. We show that movement of the slivers parallel to the subduction trench is controlled by the obliquity of plate convergence and is linked to prominent features of the Andes Mountains. For example, the Altiplano is located at the boundary of converging slivers at the concave bend of the central Andes, and the extending Gulf of Guayaquil is located at the boundary of diverging slivers at the convex bend of the northern Andes. Motion of a few large continental slivers therefore controls the present-day deformation of nearly the entire Andes mountain range. We also show that a 1,000-km-long section of the plate interface in northern Peru and southern Ecuador slips predominantly aseismically, a behaviour that contrasts with the highly seismic neighbouring segments. The primary characteristics of this low-coupled segment are shared by ∼ 20% of the subduction zones in the eastern Pacific Rim.

We analyzed interseismic velocity fields along the Vanuatu arc subduction zone from more than 45 GPS station measurements spanning 15 years. Convergence with respect to the Australian plate (AP) is normal to the trench, with amplitudes that vary greatly from a maximum of 170 mm a−1 at Vanikoro to 27 mm a−1 facing the D'Entrecasteaux Ridge (DER). Motions expressed relative to the Pacific plate (PP) highlight arc segmentation. Both the northern and southern segments undergo back‐arc spreading in a roughly NE‐SW direction, rotating anticlockwise and clockwise, respectively, while the central block moves eastward at a faster rate with respect to the PP than to the AP. More convergence is therefore accommodated at the eastern bound of the arc than at the Vanuatu trench. A right lateral strike‐slip movement (26 ± 1 mm a−1) along a zone normal to the trench (direction N70°) is necessary to accommodate the rate variation between the central and southern parts of the arc. Horizontal and vertical rates indicate partitioning between Malekula–southernmost Santo and central‐northern Santo blocks. Simple elastic modeling of the interseismic stage deformation gives locked zone characteristics (25° dip and 50 km width) and a 54 mm a−1 long‐term convergence rate between the AP and the central part of the Vanuatu arc from GPS horizontal and vertical velocities estimated south of the DER. The modeling does not fit the observed velocities facing the DER, probably because it does not account for the inelastic deformation associated with buoyant ridge subduction and back‐arc thrusting.

Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemic injury. Here, we report the development of scaffold-free prevascularized human heart tissue that survives in vivo transplantation and integrates with the host coronary circulation. Human embryonic stem cells (hESCs) were differentiated to cardiomyocytes by using activin A and BMP-4 and then placed into suspension on a rotating orbital shaker to create human cardiac tissue patches. Optimization of patch culture medium significantly increased cardiomyocyte viability in patch centers. These patches, composed only of enriched cardiomyocytes, did not survive to form significant grafts after implantation in vivo. To test the hypothesis that ischemic injury after transplantation would be attenuated by accelerated angiogenesis, we created \"second-generation,\" prevascularized, and entirely human patches from cardiomyocytes, endothelial cells (both human umbilical vein and hESC-derived endothelial cells), and fibroblasts. Functionally, vascularized patches actively contracted, could be electrically paced, and exhibited passive mechanics more similar to myocardium than patches comprising only cardiomyocytes. Implantation of these patches resulted in 10-fold larger cell grafts compared with patches composed only of cardiomyocytes. Moreover, the preformed human microvessels anastomosed with the rat host coronary circulation and delivered blood to the grafts. Thus, inclusion of vascular and stromal elements enhanced the in vitro performance of engineered human myocardium and markedly improved viability after transplantation. These studies demonstrate the importance of including vascular and stromal elements when designing human tissues for regenerative therapies.

ObjectiveWe evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.DesignDifferent models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver.ResultsThe different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα.ConclusionsThese findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target.Trial registration number NCT02390232.

In this study, we examined 615 host genes encoding 915 in-miRNAs as possible targets for interactions with all in-miRNAs. Host genes whose proteins are involved in esophageal, gastric, small bowel, colorectal, and breast cancer development were studied. Unique in-miRNA binding sites with a significance of p<0.0005 were found in the 5′UTRs, CDSs, and 3′UTRs of the host genes encoding proteins that are key participants in tumourigenesis. These data shed light on the interactions between miRNAs and mRNAs and on the role of candidate proteins in cancer. Therefore, our findings have potential application in the development of diagnostic and treatment methods.

We launched an array of nine freely floating submarine seismometers near the Galápagos islands, which remained operational for about two years. P and PKP waves from regional and teleseismic earthquakes were observed for a range of magnitudes. The signal-to-noise ratio is strongly influenced by the weather conditions and this determines the lowest magnitudes that can be observed. Waves from deep earthquakes are easier to pick, but the S/N ratio can be enhanced through filtering and the data cover earthquakes from all depths. We measured 580 arrival times for different raypaths. We show that even such a limited number of data gives a significant increase in resolution for the oceanic upper mantle. This is the first time an array of floating seismometers is used in seismic tomography to improve the resolution significantly where otherwise no seismic information is available. We show that the Galápagos Archipelago is underlain by a deep (about 1900 km) 200–300 km wide plume of high temperature, with a heat flux very much larger than predicted from its swell bathymetry. The decrease of the plume temperature anomaly towards the surface indicates that the Earth’s mantle has a subadiabatic temperature gradient.

In the quest for the faint primordial B-mode polarization of the Cosmic Microwave Background, three are the key requirements for any present or future experiment: an utmost sensitivity, excellent control over instrumental systematic effects and over Galactic foreground contamination. Bolometric Interferometry (BI) is a novel technique that matches them all by combining the sensitivity of bolometric detectors, the control of instrumental systematics from interferometry and a software-based, tunable, in-band spectral resolution due to its ability to perform band-splitting during data analysis (spectral imaging). In this paper, we investigate how the spectral imaging capability of BI can help in detecting residual contamination in case an over-simplified model of foreground emission is assumed in the analysis. To mimic this situation, we focus on the next generation of ground-based CMB experiment, CMB-S4, and compare its anticipated sensitivities, frequency and sky coverage with a hypothetical version of the same experiment based on BI, CMB-S4/BI, assuming that lineof-sight (LOS) frequency decorrelation is present in dust emission but is not accounted for during component separation. We show results from a Monte-Carlo analysis based on a parametric component separation method (FGBuster), highlighting how BI has the potential to diagnose the presence of foreground residuals in estimates of the tensor-to-scalar ratio r in the case of unaccounted Galactic dust LOS frequency decorrelation.

Objective: During the COVID-19 pandemic, the number of patients presenting to the emergency department (ED) declined. The main goal of this study was to compare and describe the non-COVID-19 patient's disease severity presentation during the pandemic with its pre-pandemic severity. Methods: We conducted a retrospective observational study. We selected two samples of visits: one during the first COVID-19 wave of 2020 (pandemic period, PP) and the other during the same months of 2019 (control period, CP). The primary endpoints were the comparison of severity and distribution of the Emergency Severity Index (ESI). Secondary endpoints were comparisons of specific patient characteristics (age, sex, length of the symptoms before the visits, spontaneous visits or not, return home or not). Results: The mean ESI of the visits during the PP (3.19) was statistically significantly lower (P = 0.001) than it was in the CP (3.43). These changes were more pronounced during the months of March (3.03 versus 3.33, P = 0.037) and April (2.96 versus 3.48, P < 0.001). The change in ESI was mainly due to an increase in the proportion of visits by patients with an ESI score of 3 (42% versus 28%, P < 0.001). There were no differences in the characteristics of patients except a decline in patients whose symptoms had a duration of more than 30 days (2% during PP versus 4% during CP, P = 0.03). Conclusion: The COVID-19 pandemic caused a change in the pattern of non-COVID-19 visits, with proportionally more severe presentations based on the ESI. To our knowledge, this is the first description of changes in behaviour in ED visits by specifically non-COVID-19 patients. Keywords: COVID-19, emergency visits, epidemiology, Emergency Severity Index