Based on 2D seismic profiles, multibeam and seabed grab cores acquired during the Garanti cruise in 2017, 1–5 km wide seabed giant polygons were identified in the Grenada basin, covering a total area ...of ∼55,000 km2, which is the largest area of outcropping polygonal faults (PF) ever found on Earth so far. They represent the top part of an active 700–1,200 m thick underlying polygonal fault system (PFS) formed due to the volumetric contraction of clay‐ and smectite‐rich sediments, initiated in the sub‐surface at the transition between the Early to Middle Pliocene. The short axes of the best‐fit ellipses obtained from a graphical center‐to‐center method were interpreted as the local orientation of a preferential contraction perpendicular to the creep deformation of slope sediments. In the North Grenada Basin, the polygons are relatively regular, but their short axes seem to be parallel to a N40°E extension recently evidenced in the forearc, possibly extending in the backarc, but not shown in the study area. They are most probably related to a progressive burial due to a homogeneous subsidence. In the South Grenada Basin, the polygons are more elongated and their axes are progressively rotating southeastward toward the depocenter, indicating a creep deformation toward the center of the basin created by a differential subsidence. Seabed polygons and underlying PF could thus be indicative of the deformation regime of shallow sediments related to main slopes controlled by two different basin architectures.
Key Points
Seabed giant polygons in the Grenada Basin cover the largest area (55,000 km2) ever found on Earth
The short axis of best‐fit ellipses of polygons may represent the orientation of the creep deformation of slope sediments
The north and south tectonic domains in the Grenada Basin are marked by major differences in the shape and orientation of seabed polygons
We report results from in‐situ measurements of lattice expansion during flash sintering of 3 mol% yttria stabilized tetragonal zirconia taken at the Advanced Photon Source, Argonne National ...Laboratory. The expansion is anisotropic, with the relative expansion of the a‐lattice constant exceeding that of the c‐lattice constant. The anisotropic expansion cannot be explained by thermal expansion and is consistent with predictions from ab‐initio calculations based upon the generation of vacancy‐interstitial pairs of zirconium and oxygen.
Intriguing latest Eocene land-faunal dispersals between South America and the Greater Antilles (northern Caribbean) has inspired the hypothesis of the GAARlandia (Greater Antilles Aves Ridge) land ...bridge. This landbridge, however, should have crossed the Caribbean oceanic plate, and the geological evolution of its rise and demise, or its geodynamic forcing, remain unknown. Here we present the results of a land-sea survey from the northeast Caribbean plate, combined with chronostratigraphic data, revealing a regional episode of mid to late Eocene, trench-normal, E-W shortening and crustal thickening by ∼25%. This shortening led to a regional late Eocene-early Oligocene hiatus in the sedimentary record revealing the location of an emerged land (the Greater Antilles-Northern Lesser Antilles, or GrANoLA, landmass), consistent with the GAARlandia hypothesis. Subsequent submergence is explained by combined trench-parallel extension and thermal relaxation following a shift of arc magmatism, expressed by a regional early Miocene transgression. We tentatively link the NE Caribbean intra-plate shortening to a well-known absolute and relative North American and Caribbean plate motion change, which may provide focus for the search of the remaining connection between 'GrANoLA' land and South America, through the Aves Ridge or Lesser Antilles island arc. Our study highlights the how regional geodynamic evolution may have driven paleogeographic change that is still reflected in current biology.
Using the data taken at the Pierre Auger Observatory between December 2004 and December 2012, we have examined the implications of the distributions of depths of atmospheric shower maximum (X ...sub(max)), using a hybrid technique, for composition and hadronic interaction models. We do this by fitting the distributions with predictions from a variety of hadronic interaction models for variations in the composition of the primary cosmic rays and examining the quality of the fit. Regardless of what interaction model is assumed, we find that our data are not well described by a mix of protons and iron nuclei over most of the energy range. Acceptable fits can be obtained when intermediate masses are included, and when this is done consistent results for the proton and iron-nuclei contributions can be found using the available models. We observe a strong energy dependence of the resulting proton fractions, and find no support from any of the models for a significant contribution from iron nuclei. However, we also observe a significant disagreement between the models with respect to the relative contributions of the intermediate components.
Immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes in multiple cancer types and are increasingly being used in early disease settings and in combinations of different ...immunotherapies. However, ICIs can also cause severe or fatal immune-related adverse-events (irAEs). We aimed to identify and characterise cardiovascular irAEs that are significantly associated with ICIs.
In this observational, retrospective, pharmacovigilance study, we used VigiBase, WHO's global database of individual case safety reports, to compare cardiovascular adverse event reporting in patients who received ICIs (ICI subgroup) with this reporting in the full database. This study included all cardiovascular irAEs classified by group queries according to the Medical Dictionary for Regulatory Activities, between inception on Nov 14, 1967, and Jan 2, 2018. We evaluated the association between ICIs and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC025 is the lower end of the IC 95% credibility interval, and an IC025 value of more than zero is deemed significant. This study is registered with ClinicalTrials.gov, number NCT03387540.
We identified 31 321 adverse events reported in patients who received ICIs and 16 343 451 adverse events reported in patients treated with any drugs (full database) in VigiBase. Compared with the full database, ICI treatment was associated with higher reporting of myocarditis (5515 reports for the full database vs 122 for ICIs, ROR 11·21 95% CI 9·36–13·43; IC025 3·20), pericardial diseases (12 800 vs 95, 3·80 3·08–4·62; IC025 1·63), and vasculitis (33 289 vs 82, 1·56 1·25–1·94; IC025 0·03), including temporal arteritis (696 vs 18, 12·99 8·12–20·77; IC025 2·59) and polymyalgia rheumatica (1709 vs 16, 5·13 3·13–8·40; IC025 1·33). Pericardial diseases were reported more often in patients with lung cancer (49 56% of 87 patients), whereas myocarditis (42 41% of 103 patients) and vasculitis (42 60% of 70 patients) were more commonly reported in patients with melanoma (χ2 test for overall subgroup comparison, p<0·0001). Vision was impaired in five (28%) of 18 patients with temporal arteritis. Cardiovascular irAEs were severe in the majority of cases (>80%), with death occurring in 61 (50%) of 122 myocarditis cases, 20 (21%) of 95 pericardial disease cases, and five (6%) of 82 vasculitis cases (χ2 test for overall comparison between pericardial diseases, myocarditis, and vasculitis, p<0·0001).
Treatment with ICIs can lead to severe and disabling inflammatory cardiovascular irAEs soon after commencement of therapy. In addition to life-threatening myocarditis, these toxicities include pericardial diseases and temporal arteritis with a risk of blindness. These events should be considered in patient care and in combination clinical trial designs (ie, combinations of different immunotherapies as well as immunotherapies and chemotherapy).
The Cancer Institut Thématique Multi-Organisme of the French National Alliance for Life and Health Sciences (AVIESAN) Plan Cancer 2014–2019; US National Cancer Institute, National Institutes of Health; the James C. Bradford Jr. Melanoma Fund; and the Melanoma Research Foundation.
The Eocene tectonic evolution of the easternmost Caribbean Plate (CP) boundary, that is the Lesser Antilles subduction zone (LASZ), is debated. Recents works shed light on a peculiar period of ...tectonic duality in the arc/back‐arc regions. A compressional‐to‐transpressional regime occurred in the north, while rifting and seafloor spreading occurred in Grenada basin to the south. The mechanism for this strong spatial variation and its evolution through time has yet to be established. Here, using 3‐D subduction mechanical models, we evaluate whether the change in the trench‐curvature radius at the northeast corner of the CP could have modulated the duality. We assume asymmetrical CP boundaries at the north (from east to west: oblique subduction to strike‐slip) and at the south (subduction‐transform edge propagator‐like behavior). Regardless of the imposed trench curvature, the southern half of our modeled CP undergoes a NW‐to‐W‐oriented extension due to the tendency of the southernmost part of the South‐America oceanic slab to rollback. In contrast, the tectonic regime in the northeast corner of the CP depends on the trench‐curvature radius. A low radius promotes transtension‐to‐transpression, with a NE‐oriented compressive component of the principal stress. A high radius largely reduces the compressive component and promotes an extensional regime similar to that in the south. We thus propose that an initially low‐curvature radius of the NE‐LASZ triggered the tectonic N‐S duality in the Eocene and led to an ephemeral period of transpression/compression at the north. However, an additional mechanism might have been required to locally enhance compression.
Key Points
The trench curvature at the northeast Caribbean plate affects the back‐arc tectonic regime in models of the Lesser Antilles subduction zone
A low‐radius of curvature induces a strong north‐south variation in the stress field, and may have favored a transpressive regime at north
A high‐radius of curvature reduces the spatial variation in the tectonic regime and induces NW‐to‐E‐oriented extension from north to south
Oblique collision of buoyant provinces against subduction zones frequently results in individualizing and rotating regional‐scale blocks. In contrast, the collision of the Bahamas Bank against the ...Northeastern Caribbean Plate increased the margin convexity triggering forearc fragmentation into small‐scale blocks. This deformation results in a prominent sequence of V‐shaped basins that widens trenchward separated by elevated spurs, in the Northern Lesser Antilles (NLA, i.e., Guadeloupe to Virgin Island). In absence of deep structure imaging, various competing models were proposed to account for this Basins‐and‐Spurs System. However, high‐resolution bathymetric and deep multichannel seismic data acquired during cruises ANTITHESIS 1‐3, reveal a drastically different tectonic evolution of the NLA Forearc.
During Eocene‐Oligocene time, the Caribbean Northeastern Boundary accommodated the Bahamas Bank collision and the subsequent margin convex bending by major left‐lateral strike‐slip faults systems in the Greater Antilles and by trench‐parallel extension along N40°–90°‐trending normal faults in the NLA. Block rotations, forearc fracturing, and V‐shaped valleys opening went along with this tectonic phase, which ends up with tectonic uplifts and an earliest‐middle Miocene regional emersion phase. Post middle Miocene regional subsidence and tectonic extension in the forearc are partly accommodated along the newly imaged N300°‐trending, 200‐km‐long normal Tintamarre Faults Zone. This drastic subsidence phase reveals vigorous margin basal erosion, which likely generated the synchronous westward migration of the volcanic arc. Thus, unlike widely accepted previous theoretical models, the NE‐SW faulting and the prominent V‐shaped valleys result from a past and sealed tectonic phase related to the margin bending and subsequent blocks rotation.
Key Points
The N. Lesser Antilles has undergone Eocene‐Oligocene NW‐SE extention and post mid Miocene NE‐SW extension separated by a regional emersion
Fault‐bounded V‐Shaped valleys result from past and sealed NW‐SE extention due to Bahamas Bank collision, margin bending, and blocks rotation
Drastic post mid Miocene subsidence and synchronous westward migration of the volcanic arc reveal vigorous subduction‐related margin erosion
We report the INTernational Gamma-ray Astrophysics Laboratory (INTEGRAL) detection of the short gamma-ray burst GRB 170817A (discovered by Fermi-GBM) with a signal-to-noise ratio of 4.6, and, for the ...first time, its association with the gravitational waves (GWs) from binary neutron star (BNS) merging event GW170817 detected by the LIGO and Virgo observatories. The significance of association between the gamma-ray burst observed by INTEGRAL and GW170817 is 3.2 , while the association between the Fermi-GBM and INTEGRAL detections is 4.2 . GRB 170817A was detected by the SPI-ACS instrument about 2 s after the end of the GW event. We measure a fluence of (1.4 0.4 0.6) × 10−7 erg cm−2 (75-2000 keV), where, respectively, the statistical error is given at the 1 confidence level, and the systematic error corresponds to the uncertainty in the spectral model and instrument response. We also report on the pointed follow-up observations carried out by INTEGRAL, starting 19.5 hr after the event, and lasting for 5.4 days. We provide a stringent upper limit on any electromagnetic signal in a very broad energy range, from 3 keV to 8 MeV, constraining the soft gamma-ray afterglow flux to <7.1 × 10−11 erg cm−2 s−1 (80-300 keV). Exploiting the unique capabilities of INTEGRAL, we constrained the gamma-ray line emission from radioactive decays that are expected to be the principal source of the energy behind a kilonova event following a BNS coalescence. Finally, we put a stringent upper limit on any delayed bursting activity, for example, from a newly formed magnetar.
We investigate the relationship between the long‐term (Quaternary) interplate coupling and the short‐term geodetically derived interseismic coupling at the Central Ecuador subduction zone. At this ...nonaccretionary margin, the Cabo Pasado shelf promontory and coastal area are associated with two inter‐plate geodetically locked patches. The deepest patch ruptured co‐seismically during the Mw7.8‐2016 Pedernales earthquake, while the shallowest underwent dominantly after‐slip. Marine geophysical and chronostratigraphic data allow reconstructing the Quaternary tectonic evolution of the shelf promontory and substantiating variation of the long‐term inter‐plate coupling that led to the geodetically locked patches. Prior to ∼1.8 Ma, the outer‐wedge inter‐plate coupling was strong enough to activate trench‐subparallel strike‐slip faults. Then, between ∼1.8 and 0.79 Ma, shortening and uplift affected the shelf promontory, implying a locally increased inter‐plate coupling. After a short, post‐0.79 Ma period of subsidence, shortening and uplift resumed denoting a high inter‐plate coupling that endured up to the present. The synchronicity of the structural evolution of the shelf promontory with the subduction chronology of two reliefs of the Carnegie Ridge crest suggests that the locked patches are caused by a geometrical resistance to subduction that propagates landward causing permanent deformation. In 2016, the deepest subducted relief localized stress accumulation and high seismic slip, while the shallowest relief, which is associated with a weakened outer‐wedge, prevented updip rupture propagation. Thus, at nonaccretionary margins, active outer‐wedge strike‐slip faults might be considered a proxy of near‐trench coupling, and subducted relief a cause of plate coupling but an obstacle to the tsunami genesis when the relief is shallow.
Plain Language Summary
The 2016‐Ecuador earthquake ruptured a subduction fault segment previously locked for decades beneath the coastline. The rupture was arrested updip by another locked fault segment called locked patch, which instead slipped slowly. To understand the cause of the locked patches, their rupture behaviors, and whether the decadal fault locking and long‐term subduction processes are related, we reconstructed the Quaternary tectonic evolution of the margin offshore Central Ecuador using geophysical data. We consider that tectonic deformation reflects the long‐term inter‐plate coupling, which is the ability of the fault to transfer long‐term stress and strain to the margin. Prior to ∼1.8 Ma, a trench‐subparallel fault accommodating lateral displacement indicates a shallow plate coupling, which increased locally between ∼1.8 and 0.79 Ma as shown by margin shortening. After a brief subsidence, shortening resumed, denoting a strong coupling that persisted until today in the form of the locked patches. Although many physical factors have been proposed to control plate coupling, here we find that the locked patches are caused by the subduction of two reliefs of a submarine ridge. Remarkably, in 2016, the deepest relief released high elastic strain, while the shallower relief, thrust under a weakened outer‐margin, damped updip rupture propagation, impeding a significant tsunami.
Key Points
A trench‐parallel strike‐slip fault and its earthquake‐controlled fault scarps substantiate a pre‐1.8 Ma, outer‐wedge inter‐plate coupling
From 1.8 Ma, a robust shelf uplift caused by subducted reliefs highlights a long‐term coupling that led to geodetically locked patches
The shallowest subducted relief likely impeded the generation of a major tsunami during the Mw 7.8, 2016 event
Immune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities have been described, but the spectrum, timing, and clinical ...presentation of these complications are not well understood. We used the World Health Organization's pharmacovigilance database of individual‐case‐safety‐reports (ICSRs) of adverse drug reactions, VigiBase, to identify cases of hematologic toxicities complicating immune checkpoint inhibitor therapy. We identified 168 ICSRs of immune thrombocytopenic purpura (ITP), hemolytic anemia (HA), hemophagocytic lymphohistiocytosis, aplastic anemia, and pure red cell aplasia in 164 ICSRs. ITP (n = 68) and HA (n = 57) were the most common of these toxicities and occurred concomitantly in four patients. These events occurred early on treatment (median 40 days) and were associated with fatal outcome in 12% of cases. Ipilimumab‐based therapy (monotherapy or combination with anti‐programmed death‐1 PD‐1) was associated with earlier onset (median 23 vs. 47.5 days, p = .006) than anti‐PD‐1/programmed death ligand‐1 monotherapy. Reporting of hematologic toxicities has increased over the past 2 years (98 cases between January 2017 and March 2018 vs. 70 cases before 2017), possibly because of increased use of checkpoint inhibitors and improved recognition of toxicities. Future studies should evaluate incidence of hematologic toxicities, elucidate risk factors, and determine the most effective treatment algorithms.
Key Points
Immune‐mediated hematologic toxicities are a potential side effect of immune checkpoint inhibitors (ICIs).
Providers should monitor complete blood counts during treatment with ICIs.
Corticosteroids are the mainstay of treatment for immune‐mediated hematologic toxicities.
Further research is needed to define patient‐specific risk factors and optimal management strategies for hematologic toxicities.
Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with cancer but related hematologic toxicities have been poorly described. Using VigiBase, the World Health Organization's pharmacovigilance database of individual case safety reports of adverse drug reactions, this study aimed to identify such cases of hematologic toxicities.
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