Crustal inheritance and a top-down control on arc magmatism at Mount St. Helens

In a subduction zone, the volcanic arc marks the location where magma, generated via flux melting in the mantle wedge, migrates through the crust and erupts. While the location of deep magma broadly defines the arc position, here we argue that crustal structures, identified in geophysical data from the Washington Cascades magmatic arc, are equally important in controlling magma ascent and defining the spatial distribution and compositional variability of erupted material. As imaged by a three-dimensional resistivity model, a broad lower-crustal mush zone containing 3-10% interconnected melt underlies this segment of the arc, interpreted to episodically feed upper-crustal magmatic systems and drive eruptions. Mount St. Helens is fed by melt channeled around a mid-Tertiary batholith also imaged in the resistivity model and supported by potential-field data. Regionally, volcanism and seismicity are almost exclusive of the batholith, while at Mount St. Helens, along its margin, the ascent of viscous felsic melt is enabled by deep-seated metasedimentary rocks. Both the anomalous forearc location and composition of St. Helens magmas are products of this zone of localized extension along the batholith margin. This work is a compelling example of inherited structural control on local stress state and magmatism

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya

IntroductionGlobally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies.MethodsHealthy women ages 18–34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition.ResultsAmong 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36–90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and −27.1% to −20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively).ConclusionTFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR.Clinical Trial RegistrationNCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382

Aspergillus mural endocarditis presenting with multiple cerebral abscesses

Abstract Background Fungal endocarditis is a rare and lethal cardiac infection which most commonly presents in immunocompromised patients or patients with other predisposing conditions. In a small subset of these patients, lesions present as mural masses and do not have any involvement with native valves or implanted devices. Here we present one such case which was diagnosed in the antemortem period in time to be managed with surgical resection. Case presentation A 70 year-old female patient who presented with multiple cerebral abscesses and was found on echocardiography to have a mass along the inferior wall of the left ventricle. She underwent surgical resection which revealed an Aspergillus vegetation along the left ventricle wall without any involvement of the cardiac valves. An intraoperative photograph was obtained and is presented in this case. The patient was started on antifungal therapy and expired on day 30 of treatment. Conclusions Fungal endocarditis is a rare yet lethal disease. It can be difficult to detect and workup should be initiated immediately if there is any clinical suspicion. This is especially true in any patient with predisposing conditions or any patient who presents with undiagnosed, culture-negative fevers or evidence of embolic foci. Once diagnosis is made, early initiation of antifungal therapy coupled with aggressive surgical debridement is required for any significant chance of survival

Cooperative joint inversion of magnetotelluric and microseismic data for imaging The Geysers geothermal field, California, USA

The Geysers geothermal field located in northern California, USA, is the world's largest electricity-generating geothermal facility. To delineate the spatio-temporal distribution of reservoir steam and recharge water, we have collected microseismic and magnetotelluric (MT) data using a dense array of stations in 2021. The microseismic and MT data have been inverted together using a 3D cooperative joint inversion workflow. The joint inversion exploits a cross-gradient structural constraint because electrical conductivity structures observed in the geothermal field are strongly correlated with VP/VS structures. To mitigate convergence issues associated with 3D large-scale joint inversion, the scheme is split into small manageable inversion subsets. By systematically performing the three inversion subsets and exchanging the structural information between velocity and conductivity models, the cooperative joint inversion mimics the full joint inversion. The 3D joint inversion results agree well with previous 3D microseismic and MT inversion studies. We find that the cooperative joint inversion improves overall MT images in terms of resolution and consistency with respect to the VP/VS model. The joint inversion also further reduces the MT data misfit. In contrast, the joint inversion does not significantly improve microseismic images because MT inversion produces low-resolution conductivity images with respect to microseismic images in depth of investigation (i.e., 1-5 km) and thus does not provide sufficient structural details that are required for improving microseismic images

Temporal magnetotellurics reveals mechanics of the 2012 Mount Tongariro, NZ eruption

Monitoring dynamics of volcanic eruptions with geophysics is challenging. In August and November, 2012, two small eruptions from Mount Tongariro provided a unique opportunity to image subsurface changes caused by the eruptions. A detailed magnetotelluric survey of the Tongariro volcanic complex completed prior to the eruption (2008‐2010) provides the pre‐eruption structure of the magmatic system. A subset of the initial measurement locations was reoccupied in June 2013. Significant changes were observed in phase tensor data at sites close to the eruptive centre. Although, subsurface electrical resistivity changed, geometry of the pre‐eruptive reservoir did not. These subsurface resistivity variations are interpreted as being predominantly caused by interaction of partial melt and the overlying brine layer causing volume reduction of the brine layer through phreatic eruption. The ability to detect significant changes associated with the magma reservoir suggests that magnetotellurics can be a valuable volcano monitoring tool