Mantle melting as a function of water content beneath back-arc basins

Subduction zone magmas are characterized by high concentrations of H_(2)O, presumably derived from the subducted plate and ultimately responsible for melting at this tectonic setting. Previous studies of the role of water during mantle melting beneath back-arc basins found positive correlations between the H_(2)O concentration of the mantle (H_(2)O_o ) and the extent of melting (F), in contrast to the negative correlations observed at mid-ocean ridges. Here we examine data compiled from six back-arc basins and three mid-ocean ridge regions. We use TiO_2 as a proxy for F, then use F to calculate H_(2)O_o from measured H_(2)O concentrations of submarine basalts. Back-arc basins record up to 0.5 wt % H_(2)O or more in their mantle sources and define positive, approximately linear correlations between H_(2)O_o and F that vary regionally in slope and intercept. Ridge-like mantle potential temperatures at back-arc basins, constrained from Na-Fe systematics (1350°–1500°C), correlate with variations in axial depth and wet melt productivity (∼30–80% F/wt % H_(2)O_o ). Water concentrations in back-arc mantle sources increase toward the trench, and back-arc spreading segments with the highest mean H_(2)O_o are at anomalously shallow water depths, consistent with increases in crustal thickness and total melt production resulting from high H_(2)O. These results contrast with those from ridges, which record low H_(2)O_o (<0.05 wt %) and broadly negative correlations between H_(2)O_o and F that result from purely passive melting and efficient melt focusing, where water and melt distribution are governed by the solid flow field. Back-arc basin spreading combines ridge-like adiabatic melting with nonadiabatic mantle melting paths that may be independent of the solid flow field and derive from the H_(2)O supply from the subducting plate. These factors combine significant quantitative and qualitative differences in the integrated influence of water on melting phenomena in back-arc basin and mid-ocean ridge settings

Mantle Melting as a Function of Water Content beneath the Mariana Arc

Subduction zone magmas are characterized by high concentrations of pre-eruptive H_2O, presumably as a result of an H_2Oflux originating from the dehydrating, subducting slab. The extent of mantle melting increases as a function of increasing water content beneath back-arc basins and is predicted to increase in a similar manner beneath arc volcanoes. Here, we present new data for olivine-hosted, basaltic melt inclusions from the Mariana arc that reveal pre-eruptive H_2O contents of ~1•5-6•0 wt %, which are up to three times higher than concentrations reported for the Mariana Trough back-arc basin. Major element systematics of arc and back-arc basin basalts indicate that the back-arc basin melting regime does not simply mix with wet, arc-derived melts to produce the observed range of back-arc magmatic H_2O concentrations. Simple melting models reveal that the trend of increasing extents of melting with increasing H_2O concentrations of the mantle source identified in the Mariana Trough generally extends beneath the Mariana volcanic front to higher mantle water contents and higher extents of melting. In detail, however, each Mariana volcano may define a distinct relationship between extent of melting and the H_2O content of the mantle source. We develop a revised parameterization of hydrous melting, incorporating terms for variable pressure and mantle fertility, to describe the distinct relationships shown by each arc volcano. This model is used in combination with thermobarometry constraints to show that hydrous melts equilibrate at greater depths (34-87 km) and temperatures (>1300°C) beneath the Mariana arc than beneath the back-arc basin (21-37 km), although both magma types can form from a mantle of similar potential temperature (~1350°C).The difference lies in where the melts form and equilibrate. Arc melts are dominated by those that equilibrate within the hot core of the mantle wedge, whereas back-arc melts are dominated by those that equilibrate within the shallow zone of decompression melting beneath the spreading center. Despite higher absolute melting temperatures (>1300°C), Mariana arc melts reflect lower melt productivity as a result of wet melting conditions and a more refractory mantle source

Comparison of important factors to patients recovering from pulmonary embolism and items covered in patient-reported outcome measures: A mixed-methods systematic review

ObjectiveUp to 50 % of patients recovering from pulmonary embolism (PE) experience negative long-term outcomes. Patient-reported outcome measures (PROMs) are important in identifying what matters to patients. We aimed to identify PROMs used in clinical studies and recommended by the International Consortium of Health Outcomes (ICHOM) and compare individual items with factors considered important by patients recovering from PE.MethodsThis was a convergent mixed-methods systematic review, including quantitative studies, using PROMs and qualitative studies with non-cancer-related PE patients. Items from each PROM and qualitative findings were categorised using an International Classification of Function linking process to allow for integrated synthesis.ResultsA total of 68 studies using 34 different PROMs with 657 items and 13 qualitative studies with 408 findings were included. A total of 104 individual ICF codes were used, and subsequently sorted into 20 distinct categories representing patient concerns. Identified PROMs were found to adequately cover 17/20 categories, including anxiety, fear of bleeding, stress, depression, dizziness/nausea, sleep disturbance, pain, dyspnea, fatigue, activity levels, family and friends, socializing, outlook on life, and medical treatment. PROMs from the ICHOM core set covered the same categories, except for dizziness/nausea.ConclusionsNo single PROM covered all aspects assessed as important by the PE population. PROMs recommended in the ICHOM core set cover 16/20 aspects. However, worrisome thoughts, hypervigilance around symptoms, and uncertainty of illness were experienced by patients with PE but were not covered by PROMS

Design and rationale of FLAVOUR: A phase IIa efficacy study of the 5-lipoxygenase activating protein antagonist AZD5718 in patients with recent myocardial infarction

levels is the primary efficacy outcome. FLAVOUR also aims to evaluate whether AZD5718 can improve coronary microvascular function, as measured by transthoracic colour Doppler-assisted coronary flow velocity reserve. Centrally pretrained study sonographers use standardized protocols and equipment. Additional outcomes include assessment of comprehensive echocardiographic parameters (including coronary flow, global strain, early diastolic strain rate and left ventricular ejection fraction), arterial stiffness, biomarkers, health-related quality of life, and safety. Specific anti-inflammatory therapies may represent novel promising treatments to reduce residual risk in patients with coronary artery disease. By combining primary pharmacodynamic and secondary cardiovascular surrogate efficacy outcomes, FLAVOUR aims to investigate the mechanistic basis and potential benefits of AZD5718 treatment in patients with coronary artery disease

The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species.

In biology and biomedicine, relating phenotypic outcomes with genetic variation and environmental factors remains a challenge: patient phenotypes may not match known diseases, candidate variants may be in genes that haven\u27t been characterized, research organisms may not recapitulate human or veterinary diseases, environmental factors affecting disease outcomes are unknown or undocumented, and many resources must be queried to find potentially significant phenotypic associations. The Monarch Initiative (https://monarchinitiative.org) integrates information on genes, variants, genotypes, phenotypes and diseases in a variety of species, and allows powerful ontology-based search. We develop many widely adopted ontologies that together enable sophisticated computational analysis, mechanistic discovery and diagnostics of Mendelian diseases. Our algorithms and tools are widely used to identify animal models of human disease through phenotypic similarity, for differential diagnostics and to facilitate translational research. Launched in 2015, Monarch has grown with regards to data (new organisms, more sources, better modeling); new API and standards; ontologies (new Mondo unified disease ontology, improvements to ontologies such as HPO and uPheno); user interface (a redesigned website); and community development. Monarch data, algorithms and tools are being used and extended by resources such as GA4GH and NCATS Translator, among others, to aid mechanistic discovery and diagnostics

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways