New insights into landslide processes around volcanic islands from Remotely Operated Vehicle (ROV) observations offshore Montserrat

Submarine landslide deposits have been mapped around many volcanic islands, but interpretations of their structure, composition, and emplacement are hindered by the challenges of investigating deposits directly. Here we report on detailed observations of four landslide deposits around Montserrat collected by Remotely Operated Vehicles, integrating direct imagery and sampling with sediment core and geophysical data. These complementary approaches enable a more comprehensive view of large-scale mass-wasting processes around island-arc volcanoes than has been achievable previously. The most recent landslide occurred at 11.5–14 ka (Deposit 1; 1.7 km3) and formed a radially spreading hummocky deposit that is morphologically similar to many subaerial debris-avalanche deposits. Hummocks comprise angular lava and hydrothermally altered fragments, implying a deep-seated, central subaerial collapse, inferred to have removed a major proportion of lavas from an eruptive period that now has little representation in the subaerial volcanic record. A larger landslide (Deposit 2; 10 km3) occurred at ∼130 ka and transported intact fragments of the volcanic edifice, up to 900 m across and over 100 m high. These fragments were rafted within the landslide, and are best exposed near the margins of the deposit. The largest block preserves a primary stratigraphy of subaerial volcanic breccias, of which the lower parts are encased in hemipelagic mud eroded from the seafloor. Landslide deposits south of Montserrat (Deposits 3 and 5) indicate the wide variety of debris-avalanche source lithologies around volcanic islands. Deposit 5 originated on the shallow submerged shelf, rather than the terrestrial volcanic edifice, and is dominated by carbonate debris

CRF1-R Activation of the Dynorphin/Kappa Opioid System in the Mouse Basolateral Amygdala Mediates Anxiety-Like Behavior

Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF) were triggered by CRF1-R activation of the dynorphin/kappa opioid receptor (KOR) system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM). The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF1-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF2-R agonist urocortin III did not affect open arm time, and mice lacking CRF2-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF2-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF1-R activation may mediate anxiety and CRF2-R may encode aversion. Using a phosphoselective antibody (KORp) to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype, but not in mice pretreated with the selective CRF1-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was surprising, and these results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced anxiety behaviors and aversive behaviors via different mechanisms

The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer

The third-generation aromatase inhibitors (AIs) anastrozole, exemestane and letrozole have largely replaced tamoxifen as the preferred treatment for hormone receptor – positive breast cancer in postmenopausal women. Approximately 185,000 new cases of invasive breast cancer are diagnosed yearly, and at least half of these women are both postmenopausal and eligible for adjuvant therapy with AIs. In addition, AIs are currently being tested as primary prevention therapy in large randomised trials involving tens of thousands of women at increased risk for breast cancer. Given the volume of use, internists will increasingly see postmenopausal women who are taking or considering treatment with AIs. Physicians need to be able to: (i) briefly discuss the pros and cons of using a selective estrogen receptor modulator such as tamoxifen or raloxifene vs. an AI for risk reduction and (ii) recognise and manage AI-associated adverse events. The primary purpose of this review is to help internists with these two tasks

Early Cretaceous vegetation and climate change at high latitude: Palynological evidence from Isachsen Formation, Arctic Canada

Quantitative palynology of the marginal marine and deltaic-fluvial Isachsen Formation of the Sverdrup Basin, Canadian Arctic, provides insight into high latitude climate during much of the Early Cretaceous (Valanginian to early Aptian). Detrended Correspondence Analysis of main pollen and spore taxa is used to derive three ecological groupings influenced by moisture and disturbance based on the botanical affinities of palynomorphs: 1) a mixed coniferous assemblage containing both lowland and upland components; 2) a conifer-filicopsid community that likely grew in dynamic lowland habitats; and, 3) a mature dry lowland community composed of Cheirolepidiaceans. Stratigraphic changes in the relative abundance of pollen and spore taxa reflect climate variability in this polar region during the ~20 Mya history of the Isachsen Formation. The late Valanginian was relatively cool and moist and promoted lowland conifer-filicopsid communities. Warming in the Hauterivian resulted in the expansion coniferous communities in well-drained or arid hinterlands. A return to relatively cool and moist conditions in the Barremian resulted in the expansion of mixed lowland communities. This work demonstrates the utility of a multivariate statistical approach to palynology to provide insight into the composition and dynamics of ecosystems and climate of high latitude regions during the Early Cretaceous

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease