Subduction dynamics: Constraints from gravity field observations

Satellite systems do the best job of resolving the long wavelength components of the Earth's gravity field. Over the oceans, satellite-borne radar altimeters such as SEASAT provide the best resolution observations of the intermediate wavelength components. Satellite observations of gravity contributed to the understanding of the dynamics of subduction. Large, long wavelength geoidal highs generally occur over subduction zones. These highs are attributed to the superposition of two effects of subduction: (1) the positive mass anomalies of subducting slabs themselves; and (2) the surface deformations such as the trenches convectively inducted by these slabs as they sink into the mantle. Models of this subduction process suggest that the mantle behaves as a nonNewtonian fluid, its effective viscosity increases significantly with depth, and that large positive mass anomalies may occur beneath the seismically defined Benioff zones

On the compensation of geoid anomalies due to subducting slabs

Candidate models of the forces which oppose the sinking of slabs are all constrained to produce results consistent with the following observation: relative geoid highs, which one assumes are due to slabs, characteristically occur over subduction zones. Certain models which are otherwise plausible, such as those based on a Newtonian half-space mantle, yield geoid lows instead of highs. This study has extended a published model of viscous corner flow in subduction zones in order to demonstrate that it can, in certain cases, produce the requisite geoid highs. Specifically the relative geoid highs are produced if mantle flow is distinctly non-Newtonian (stress exponent n 2). Results in the form of deflection on vertical (or geoid slope) profiles are computed for typical values of the slab parameters; they are compared with a representative profile of geoid slopes derived from Seasat altimeter data in order to show qualitative similarities. It is concluded that the effect of non-Newtonian flow as opposed to Newtonian, is to spread out the induced surface deformation, thereby stretching out the regional compensation to wavelengths, (transverse to the trench) of several thousand kilometers

Geoid anomalies in the vicinity of subduction zones

The regional geoid of the southwest Pacific is matched reasonably well by results from a model of the upper mantle density structure (including slabs) associated with subduction zones of the region. Estimates of the geoid are obtained from Geos-3 and Seasat radar altimeter data. These data are very well suited to the task of detecting intermediate wavelength (600-4000 km) geopotential variations. Actually, subducting slabs can be expected to produce primarily intermediate and longer wavelength variations. Gravimetric profiles across trench/island arc complexes resolve primarily short wavelengths. The model represents subducting slabs as thin surfaces of anomalous mass per unit area. These surfaces are positioned using published seismicity results which detail the configuration of the Benioff zones. Crustal effects are ignored. Effects due to the contrast between the young thermal lithosphere of the behind-arc regions (marginal basins) and the older lithosphere seaward of the trench are modelled. Results indicate that the New Hebrides slab possesses an average areal density anomaly of about 300,000 gm/sq cm. This is about three times that which is estimated for the Tonga-Kermadec slab. Additional modelling suggests that slabs worldwide may be an important source of large, long wavelength gravity highs; i.e., they may contribute substantially to geopotential power of harmonic degree as low as three or four up to twenty or more

Geodynamics and temporal variations in the gravity field

Just as the Earth's surface deforms tectonically, so too does the gravity field evolve with time. Now that precise geodesy is yielding observations of these deformations it is important that concomitant, temporal changes in the gravity field be monitored. Although these temporal changes are minute they are observable: changes in the J2 component of the gravity field were inferred from satellite (LAGEOS) tracking data; changes in other components of the gravity field would likely be detected by Geopotential Research Mission (GRM), a proposed but unapproved NASA gravity field mission. Satellite gradiometers were also proposed for high-precision gravity field mapping. Using simple models of geodynamic processes such as viscous postglacial rebound of the solid Earth, great subduction zone earthquakes and seasonal glacial mass fluctuations, we predict temporal changes in gravity gradients at spacecraft altitudes. It was found that these proposed gravity gradient satellite missions should have sensitivities equal to or better than 10(exp -4) E in order to reliably detect these changes. It was also found that satellite altimetry yields little promise of useful detection of time variations in gravity

SEASAT observations of lithospheric flexure seaward of trenches

Lithospheric flexure seaward of deep ocean trenches in SEASAT altimeter observations of the marine geoid. In fact, mechanical models of lithospheric flexure can be tested directly on the SEASAT altimeter data. A simple elastic model was used for the oceanic lithosphere and, after least squares adjustments, estimates of model parameters were recovered including Outer Rise (OR) amplitude, OR wavelength, and effective lithospheric thickness. Effective lithospheric thickness was recovered for five regions: the Mariana, the Kuril, the Philippine, the Aleutian and the Middle America OR. These results support the suggestion of Bodine et al. (1981) that effective thickness, T, increased with age of lithosphere in approximate accord with the relation T approximately equals x age to the 1/2 power where C approximately equals 4 km x my to the -1/2 power. Altimetric results agree more closely with this relation than do published results based on bathymetric data. The close agreement with the thickness-age relation suggests that there is no longer any need to assume that significant horizontal compression acts across the Kuril, Marianas and Izo-Bonin trenches. This thickness-age relation implies that flexural strength of the oceanic lithosphere is temperature controlled

Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis

Experimental autoimmune vasculitis (EAV) is a model of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) induced by immunisation of susceptible rat strains with myeloperoxidase (MPO). Animals develop circulating MPO-ANCA, pulmonary haemorrhage and glomerulonephritis, although renal injury is mild and recovers spontaneously without treatment. In this study we aimed to augment the severity of glomerulonephritis. Following induction of EAV on day 0, a sub-nephritogenic dose of nephrotoxic serum (NTS) containing heterologous antibodies to glomerular basement membrane was administered on day 14. This resulted in a significant increase in disease severity at day 28 compared to MPO immunisation alone - with more urinary abnormalities, infiltrating glomerular leucocytes, and crescent formation that progressed to glomerular and tubulointerstitial scarring by day 56, recapitulating important features of human disease. Importantly, the glomerulonephritis remained pauci-immune, and was strictly dependent on the presence of autoimmunity to MPO, as there was no evidence of renal disease following administration of sub-nephritogenic NTS alone or after immunisation with a control protein in place of MPO. Detailed phenotyping of glomerular leucocytes identified an early infiltrate of non-classical monocytes following NTS administration that, in the presence of autoimmunity to MPO, may initiate the subsequent influx of classical monocytes which augment glomerular injury. We also showed that this model can be used to test novel therapeutics by using a small molecule kinase inhibitor (fostamatinib) that rapidly attenuated both glomerular and pulmonary injury over a four-day treatment period. We believe that this enhanced model of MPO-AAV will prove useful for the study of glomerular leucocyte behaviour and novel therapeutics in AAV in the future. This article is protected by copyright. All rights reserved

Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period

Syk activation in circulating and tissue innate immune cells in antineutrophil cytoplasmic antibody-associated vasculitis

OBJECTIVE: Syk is a cytoplasmic protein tyrosine kinase that plays a role in signaling via B cell and Fc receptors (FcR). FcR engagement and signaling via Syk is thought to be important in antineutrophil cytoplasm antibody (ANCA) IgG-mediated neutrophil activation. This study was undertaken to investigate the role of Syk in ANCA-induced myeloid cell activation and vasculitis pathogenesis. METHODS: Phosphorylation of Syk in myeloid cells from healthy controls and ANCA-associated vasculitis (AAV) patients was analyzed using flow cytometry. The effect of Syk inhibition on myeloperoxidase (MPO)-ANCA IgG activation of cells was investigated using functional assays (interleukin-8 and reactive oxygen species production) and targeted gene analysis with NanoString. Total and phosphorylated Syk at sites of tissue inflammation in patients with AAV was assessed using immunohistochemistry and RNAscope in situ hybridization. RESULTS: We identified increased phosphorylated Syk at critical activatory tyrosine residues in blood neutrophils and monocytes from patients with active AAV compared to patients with disease in remission or healthy controls. Syk was phosphorylated in vitro following MPO-ANCA IgG stimulation, and Syk inhibition was able to prevent ANCA-mediated cellular responses. Using targeted gene expression analysis, we identified up-regulation of FcR- and Syk-dependent signaling pathways following MPO-ANCA IgG stimulation. Finally, we showed that Syk is expressed and phosphorylated in tissue leukocytes at sites of organ inflammation in AAV. CONCLUSION: These findings indicate that Syk plays a critical role in MPO-ANCA IgG-induced myeloid cell responses and that Syk is activated in circulating immune cells and tissue immune cells in AAV; therefore, Syk inhibition may be a potential therapeutic option

Risk factors for severe outcomes in patients with systemic vasculitis & COVID‐19: a bi‐national registry‐based cohort study

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and so may be at risk of severe outcomes following COVID-19. It is important to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multi-centre cohort was developed through the participation of centres affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes were described. Logistic regression was used to evaluate associations between potential risk factors and severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, invasive ventilation, or death. RESULTS: Sixty-five cases of patients with systemic vasculitis who developed COVID-19 were reported (median age 70 years, 49% female) of whom 25 (38%) experienced a severe outcome. Most cases (55/65, 85%) had ANCA-associated vasculitis (AAV). Almost all patients required hospitalization (59/65, 91%), 7 patients (11%) were admitted to intensive care and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcome (adjusted odds ratio [aOR] 3.7 (1.1-14.9, p=0.047)) as was comorbid respiratory disease (aOR 7.5 (1.9-38.2, p=0.006)). Vasculitis disease activity and non-glucocorticoid immunosuppression were not associated with severe outcome. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision making relating to risk of severe COVID-19 in this vulnerable patient group