Surface Wavefield Tomography of the Alpine Region to Constrain Slab Geometries, Lithospheric Deformation and Asthenospheric Flow

Surface waves radiated by teleseismic earthquakes are ideally suited to constrain isotropic and anisotropic elastic properties of the upper mantle down to about 300 km depth beneath dense networks of broad-band stations. Rayleigh wave phase velocities were automatically determined in a broad period range from 8 s to 300 s and a very strict quality control was applied. This resulted in a data set of more than 200,000 inter-station phase velocity curves. Local dispersion curves, extracted from phase velocity maps were inverted for a 3D shear-wave velocity model (MeRE2020) using a newly developed stochastic inversion algorithm based on particle swarm optimization. It was shown that the presence of small and highly segmented slabs can be resolved by surface wave tomography in case of a high station density. In the western Alps, a short Eurasian slab was imaged down to about 150 km depth, whereas at larger depths a pronounced low velocity anomaly indicates slab break-off. In the northern Apennines, a nearly vertical south-dipping slab connected to the Adriatic mantle lithosphere beneath the Po Basin is observed. In the central Alps, the presence of Eurasian mantle lithosphere is found down to the bottom of the model at 300 km depth. Whereas in the eastern Alps, a short Eurasian nearly vertical dipping slab is found down to only 150 km depth. The presence of a short slab consisting of Adriatic mantle lithosphere is also indicated beneath the northern Dinarides extending towards the Alps east of the Giudicaria fault. Anisotropic phase velocity maps show at 25 s period (lower crustal depth) mostly fast orogen parallel directions, whereas in the western Alps azimuthal anisotropy is more inclined with respect to the Alpine arc. At 100 s period, azimuthal anisotropy beneath the western Alps indicates asthenospheric flow towards the Ligurian Sea and beneath the northern Dinarides towards the Pannonian Basin through slab gaps. Moreover, seismic wavefields were analysed using AlpArray and Swath-D data. Wavefield animations illustrate the considerable spatio-temporal variability of the wavefield's properties at a lateral resolution down to about 100km. Within denser station distributions like those provided by Swath-D, even shorter period body and surface wave features can be recovered. Considerable amplifications of the Rayleigh wave in the Alpine area are observed for several earthquakes. To analyse Rayleigh wave quantitatively, an algorithm has been developed to extract their phase and amplitude fields using cross correlation between synthetic waveforms and recordings of a dense array. Phase fields are unwrapped by solving a linear system of equations. Phase and amplitude fields are quality controlled and interpolated to determine structural phase velocity fields using Helmholtz tomography. It is shown that the observed amplitude fields depend heavily on lateral heterogeneity outside the array. Often, linear amplifications in the propagation direction are observed. In order to model the observed wavefields, the AxiSEM-SPECFEM Coupling algorithm has been improved and adapted concerning flexibility and efficiency, reducing the necessary wavefield interpolation significantly and allowing topography as well as existing 3D Models of the Alpine region to be easily implemented

The small-molecule inhibitor MRIA9 reveals novel insights into the cell cycle roles of SIK2 in ovarian cancer cells

The activity of the Salt inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK)-related kinase family, has been linked to several biological processes that maintain cellular and energetic homeostasis. SIK2 is overexpressed in several cancers, including ovarian cancer, where it promotes the proliferation of metastases. Furthermore, as a centrosome kinase, SIK2 has been shown to regulate the G2/M transition, and its depletion sensitizes ovarian cancer to paclitaxel-based chemotherapy. Here, we report the consequences of SIK2 inhibition on mitosis and synergies with paclitaxel in ovarian cancer using a novel and selective inhibitor, MRIA9. We show that MRIA9-induced inhibition of SIK2 blocks the centrosome disjunction, impairs the centrosome alignment, and causes spindle mispositioning during mitosis. Furthermore, the inhibition of SIK2 using MRIA9 increases chromosomal instability, revealing the role of SIK2 in maintaining genomic stability. Finally, MRIA9 treatment enhances the sensitivity to paclitaxel in 3D-spheroids derived from ovarian cancer cell lines and ovarian cancer patients. Our study suggests selective targeting of SIK2 in ovarian cancer as a therapeutic strategy for overcoming paclitaxel resistance

Depression and anxiety with exposure to ozone and particulate matter : an epidemiological claims data analysis

Background: Depression and anxiety have complex etiologies and are associated with a significant burden of disease. Although air pollution has been hypothesized as a possible risk factor of these disorders, the associations are still under-investigated. We aimed to analyze associations between long-term exposure to ambient ozone and particulate matter with diameter< 10 mu m (PM10) and diagnoses of depression and anxiety in a general population.Methods: We utilized data from a large statutory health insurance company from Saxony, Germany. Information on outpatient clinical diagnoses of depression and anxiety was available for the years 2005-2014. We assigned ambient ozone and PM10 estimates to residential districts of 1.13 million individuals aged 16 and older. Depression and anxiety were defined as diagnoses counts. Associations with depression and anxiety were assessed using adjusted generalized estimating equations models.Results: In the ten-year study period, the observed prevalences of depression and anxiety were 7.40% and 3.82%, respectively. In the two-pollutant model, 10 more days with a maximum 8-h average ozone concentration exceeding 120 mu g/m(3) resulted in a relative risk (RR) of 1.010 with 95% confidence interval (CI) (1.005, 1.014) for depression and an RR of 1.007 (95% CI (1.000, 1.014)) for anxiety. The effect estimates of PM10 for depression and anxiety were 1.180 (95% CI (1.160, 1.201)) and 1.176 (95% CI (1.148, 1.205)) per 10 mu g/m(3) increase in PM10 concentration, respectively. Age, sex, and access to healthcare of the individual were also associated with the diagnosis of the disorders. The associations were consistent across one- and two-pollutant models.Conclusions: Our findings indicate that increased levels of ambient ozone and PM10 may elevate the risk of a depression or anxiety diagnosis in the general population. However, given the lack of data on individual air pollutant exposure and socioeconomic status, our results should be interpreted with caution. Further well-designed epidemiological studies should replicate our findings

Cytoreductive treatment in real life: a chart review analysis on 1440 patients with polycythemia vera

Purpose!#!Patients with polycythemia vera (PV) show an elevated incidence of thromboembolic complications and decreased survival when compared to age-matched healthy individuals. Hypercellularity as indicated by elevated hematocrit, pathophysiological changes induced by the JAK2 driver mutation and cardiovascular risk factors contribute to the increased incidence of thromboembolic events. Higher age and a history of thromboembolic events define a high-risk population of PV patients. Depending on the individual risk profile, phlebotomy or pharmacologic cytoreduction is recommended in combination with low-dose acetylsalicylic acid. Stringent cytoreduction is required for effective risk reduction. However, in recent reports, the rate of thromboembolic complications in PV patients under cytoreductive therapy appears still elevated compared to healthy individuals. This study reports on a chart review to assess for cytoreductive therapy of 1440 PV patients in real life.!##!Methods!#!Forty-two eligible hematologists/oncologists in private practice treating patients with MPN were recruited to participate in a paper-pencil-based survey conducted between January 2019 and March 2020 in Germany. Physicians were asked to report primary documented data obtained from patient charts. Descriptive analyses were conducted to assess for patient characteristics, treatment modalities, risk factors and thromboembolic complications.!##!Results!#!Data were collected from the patient charts of 1440 individuals diagnosed with PV. The patient population was older than those reported in multicenter trials with a median age of 72.2 years at the time of reporting and 63.5 years at diagnosis. Age was the main factor accounting for high-risk status with 84.7% of patients being above the age of 60 followed by thromboembolic complications reported in 21.3% of patients. The use of pharmacologic cytoreduction was highly variable between participating centers with an average of 60.7% and a range of 10.1-100%. Hydroxyurea was the most frequently used drug followed by ruxolitinib, while interferons were reported for a minority of patients. For 35.4% of patients a persistent need for phlebotomy in addition to cytoreductive treatment was reported. Although presence of high-risk criteria and insufficient disease control were reported as main triggers to initiate pharmacologic cytoreduction, 28.1% had elevated hematocrit values (> 45%) and 38.6% showed persistence of elevated leukocyte count (> 10!##!Conclusions!#!Cytoreductive treatment of high-risk PV in real life is highly variable regarding indication for cytoreduction and definition of therapy resistance. This study highlights the need for (i) improved risk stratification for thromboembolic events, (ii) consequent indication of pharmacologic cytoreduction in high-risk PV and (iii) attention to signs of therapy resistance that can trigger an earlier and stringent switch to second line agents

Biphasic MERS-CoV Incidence in Nomadic Dromedaries with Putative Transmission to Humans, Kenya, 2022–2023

Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedaries in Africa, but camel-to-human transmission is limited. Sustained 12-month sampling of dromedaries in a Kenya abattoir hub showed biphasic MERS-CoV incidence; peak detections occurred in October 2022 and February 2023. Dromedary-exposed abattoir workers (7/48) had serologic signs of previous MERS-CoV exposure