Seismo-volcano source localization with triaxial broad-band seismic array

International audienceSeismo-volcano source localization is essential to improve our understanding of eruptive dynamics and of magmatic systems. The lack of clear seismic wave phases prohibits the use of classical location methods. Seismic antennas composed of one-component (1C) seismometers provide a good estimate of the backazimuth of the wavefield. The depth estimation, on the other hand, is difficult or impossible to determine. As in classical seismology, the use of three-component (3C) seismometers is now common in volcano studies. To determine the source location parameters (backazimuth and depth), we extend the 1C seismic antenna approach to 3Cs. This paper discusses a high-resolution location method using a 3C array survey (3CMUSIC algorithm) with data from two seismic antennas installed on an andesitic volcano in Peru (Ubinas volcano). One of the main scientific questions related to the eruptive process of Ubinas volcano is the relationship between the magmatic explosions and long-period (LP) swarms. After introducing the 3C array theory, we evaluate the robustness of the location method on a full wavefield 3-D synthetic data set generated using a digital elevation model of Ubinas volcano and an homogeneous velocity model. Results show that the backazimuth determined using the 3C array has a smaller error than a 1C array. Only the 3C method allows the recovery of the source depths. Finally, we applied the 3C approach to two seismic events recorded in 2009. Crossing the estimated backazimuth and incidence angles, we find sources located 1000 ± 660 m and 3000 ± 730 m below the bottom of the active crater for the explosion and the LP event, respectively. Therefore, extending 1C arrays to 3C arrays in volcano monitoring allows a more accurate determination of the source epicentre and now an estimate for the depth

Tremor-rich shallow dyke formation followed by silent magma flow at Bárdarbunga in Iceland

The Bárdarbunga eruption in Iceland in 2014 and 2015 produced about 1.6 km3 of lava. Magma propagated away from Bárdarbunga to a distance of 48 km in the sub-surface beneath Vatnajökull glacier, emerging a few kilometres beyond the glacier's northern rim. A puzzling observation is the lack of shallow (<3 km deep), high-frequency earthquakes associated with shallow dyke formation near the subaerial and subglacial eruptive sites, suggesting that near-surface dyke formation is seismically quiet. However, seismic array observations and seismic full wavefield simulations reveal the presence and nature of shallow, pre-eruptive, long-duration seismic tremor activity. Here we use analyses of seismic data to constrain the relationships between seismicity, tremor, dyke propagation and magma flow during the Bárðarbunga eruption. We show that although tremor is usually associated with magma flow in volcanic settings, pre-eruptive tremor at Bárdarbunga was probably caused by swarms of microseismic events during dyke formation, and hence is directly associated with fracturing of the upper 2–3 km of the crust. Subsequent magma flow in the newly formed shallow dyke was seismically silent, with almost a complete absence of seismicity or tremor. Hence, we suggest that the transition from temporarily isolated, large, deep earthquakes to many smaller, shallower, temporally overlapping earthquakes (< magnitude 2) that appear as continuous tremor announces the arrival of a dyke opening in the shallow crust, forming a pathway for silent magma flow to the Earth's surface

Source geometry from exceptionally high resolution long period event observations at Mt Etna during the 2008 eruption

During the second half of June, 2008, 50 broadband seismic stations were deployed on Mt Etna volcano in close proximity to the summit, allowing us to observe seismic activity with exceptionally high resolution. 129 long period events (LP) with dominant frequencies ranging between 0.3 and 1.2 Hz, were extracted from this dataset. These events form two families of similar waveforms with different temporal distributions. Event locations are performed by cross-correlating signals for all pairs of stations in a two-step scheme. In the first step, the absolute location of the centre of the clusters was found. In the second step, all events are located using this position. The hypocentres are found at shallow depths (20 to 700 m deep) below the summit craters. The very high location resolution allows us to detect the temporal migration of the events along a dike-like structure and 2 pipe shaped bodies, yielding an unprecedented view of some elements of the shallow plumbing system at Mount Etna. These events do not seem to be a direct indicator of the ongoing lava flow or magma upwelling

Transforming growth factor- directly induces p53-up-regulated modulator of apoptosis (PUMA) during the rapid induction of apoptosis in myc-driven B-cell lymphomas

Background: TGF-β induces apoptosis in Burkitt's lymphoma cells. Results: PUMA is a direct target gene of TGF-β signaling and is required for rapid apoptosis. Conclusion: TGF-β-mediated direct induction of PUMA contributes to apoptosis in human and murine c-Myc-driven lymphomas. Significance: These studies link TGF-β signaling and transcriptional activation of PUMA, two factors with critical roles in regulating B-cell survival

Self-care and adherence to medication: a survey in the hypertension outpatient clinic

<p>Abstract</p> <p>Background</p> <p>Self-care practices for patients with hypertension include adherence to medication, use of blood pressure self-monitoring and use of complementary and alternative therapies (CAM) The prevalence of CAM use and blood pressure self-monitoring have not been described in a UK secondary care population of patients with hypertension and their impact on adherence to medication has not been described. Adherence to medication is important for blood pressure control, but poor adherence is common. The study aimed to determine the prevalence of self-care behaviours in patients attending a secondary care hypertension clinic.</p> <p>Methods</p> <p>Cross-sectional questionnaire survey. 196 patients attending a secondary care hypertension clinic in a teaching hospital serving a multiethnic population, Birmingham, UK. Main outcome measures: Prevalence of use of CAM, home monitors, adherence to anti-hypertensive medication.</p> <p>Results</p> <p>CAM use in previous 12 months was reported by 66 (43.1%) respondents. CAM users did not differ statistically from non-CAM users by age, gender, marital status or education. Vitamins, prayer a dietary supplements were the most commonly used CAM. Nine (12.7%) women reported using herbal CAM compared to one man (1.2%), (p = 0.006). Ten (6.7%) respondents reported ever being asked by a doctor about CAM use. Perfect adherence to anti-hypertensive medication was reported by 26 (44.8%) CAM-users and 46 (60.5%) non-CAM users (p = 0.07). Being female and a CAM user was significantly associated with imperfect adherence to anti-hypertensive medication. Older and white British respondents were significantly more likely to report perfect adherence. Blood pressure monitors were used by 67 (43.8%) respondents, which was not associated with gender, CAM use or adherence to medication.</p> <p>Conclusion</p> <p>Hypertensive patients use a variety of self-care methods, including CAM, home blood pressure monitors, and adherence to prescribed medication. This study found the prevalence of CAM use in hypertensive patients was higher than in the UK population. It is important to acknowledge the self-care behaviour of hypertensive patients, in order to assess potential harm, and encourage effective methods of self-care.</p

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10 ) and AC058822.1 (P = 1.47 × 10 ), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10 ), demonstrating the importance of diversifying study cohorts. [Abstract copyright: © 2023. The Author(s).

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers