Seismology records the presence of various heterogeneities throughout the lower mantle1,2, but the origins of these signals- whether thermal or chemical-remain uncertain, and therefore much of the ...information that they hold about the nature of the deep Earth is obscured. Accurate interpretation of observed seismic velocities requires knowledge of the seismic properties of all of Earth's possible mineral components. Calcium silicate (CaSiO3) perovskite is believed to be the third most abundant mineral throughout the lower mantle. Here we simultaneously measure the crystal structure and the shear-wave and compressional-wave velocities of samples of CaSiO3 perovskite, and provide direct constraints on the adiabatic bulk and shear moduli of this material. We observe that incorporation of titanium into CaSiO3 perovskite stabilizes the tetragonal structure at higher temperatures, and that the material's shear modulus is substantially lower than is predicted by computations3-5 or thermodynamic datasets6. When combined with literature data and extrapolated, our results suggest that subducted oceanic crust will be visible as low-seismic-velocity anomalies throughout the lower mantle. In particular, we show that large low-shear-velocity provinces (LLSVPs) are consistent with moderate enrichment of recycled oceanic crust, and mid-mantle discontinuities can be explained by a tetragonal-cubic phase transition in Ti-bearing CaSiO3 perovskite.
On 17 August 2017, the Advanced LIGO and Virgo detectors observed the gravitational-wave event GW170817-a strong signal from the merger of a binary neutron-star system. Less than two seconds after ...the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO-Virgo-derived location of the gravitational-wave source. This sky region was subsequently observed by optical astronomy facilities, resulting in the identification of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first 'multi-messenger' astronomical observation. Such observations enable GW170817 to be used as a 'standard siren' (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic 'distance ladder': the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements, while being completely independent of them. Additional standard siren measurements from future gravitational-wave sources will enable the Hubble constant to be constrained to high precision.
We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy ...community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and
90
%
credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5–
20
deg
2
requires at least three detectors of sensitivity within a factor of
∼
2
of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.
Background and purpose
Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis ...(IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes.
Methods
Pulse pressure variability was calculated from 24‐h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST‐ER) trial. The outcomes of interest were the pre‐specified efficacy and safety end‐points of CLOTBUST‐ER. All associations were adjusted for potential confounders in multivariable regression models.
Results
Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24‐h neurological improvement and 90‐day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90‐day mortality (P < 0.001). Every 5‐mmHg increase in the 24‐h PP variability was independently associated with a 36% decrease in the likelihood of 90‐day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52–0.80) and a 60% increase in the odds of 90‐day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23–2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration.
Conclusions
Increased PP variability appears to be independently associated with adverse short‐term and long‐term functional outcomes of AIS patients treated with IVT.
Purpose
Follow-up infarct volume (FIV) is moderately associated with functional outcome. We hypothesized that accounting for infarct location would strengthen the association of FIV with functional ...outcome.
Methods
We included 252 patients from the HERMES collaboration with follow-up diffusion weighted imaging. Patients received endovascular treatment combined with best medical management (
n
= 52%) versus best medical management alone (
n
= 48%). FIV was quantified in low, moderate and high modified Rankin Scale (mRS)-relevant regions. We used binary logistic regression to study the relation between the total, high, moderate or low mRS-relevant FIVs and favorable outcome (mRS < 2) after 90 days. The strength of association was evaluated using the c-statistic.
Results
Small lesions only occupied high mRS-relevant brain regions. Lesions additionally occupied lower mRS-relevant brain regions if FIV expanded. Higher FIV was associated with a higher risk of unfavorable outcome, as were volumes of tissue with low, moderate and high mRS relevance. In multivariable modeling, only the volume of high mRS-relevant infarct was significantly associated with favorable outcome. The c-statistic was highest (0.76) for the models that included high mRS-relevant FIV or the combination of high, moderate and low mRS-relevant FIV but was not significantly different from the model that included only total FIV (0.75).
Conclusion
This study confirms the association of FIV and unfavorable functional outcome but showed no strengthened association if lesion location was taken into account.
Because of the lack of tissue available for islet transplantation, new sources of β-cells have been sought for the treatment of type 1 diabetes. The aim of this study was to determine whether the ...human exocrine-enriched fraction from the islet isolation procedure could be reprogrammed to provide additional islet tissue for transplantation. The exocrine-enriched cells rapidly dedifferentiated in culture and grew as a mesenchymal monolayer. Genetic lineage tracing confirmed that these mesenchymal cells arose, in part, through a process of epithelial-to-mesenchymal transitioning (EMT). A protocol was developed whereby transduction of these mesenchymal cells with adenoviruses containing Pdx1, Ngn3, MafA, and Pax4 generated a population of cells that were enriched in glucagon-secreting α-like cells. Transdifferentiation or reprogramming toward insulin-secreting β-cells was enhanced, however, when using unpassaged cells in combination with inhibition of EMT by inclusion of Rho-associated kinase (ROCK) and transforming growth factor-β1 inhibitors. Resultant cells were able to secrete insulin in response to glucose and on transplantation were able to normalize blood glucose levels in streptozotocin diabetic NOD/SCID mice. In conclusion, reprogramming of human exocrine-enriched tissue can be best achieved using fresh material under conditions whereby EMT is inhibited, rather than allowing the culture to expand as a mesenchymal monolayer.
A replenishable source of insulin-producing cells has the potential to cure type 1 diabetes. Attempts to culture and expand pancreatic β-cells in vitro have resulted in their transition from ...insulin-producing epithelial cells to mesenchymal stromal cells (MSCs) with high proliferative capacity but devoid of any hormone production. The aim of this study was to determine whether the transcription factor Krüppel-like factor 4 (KLF4), could induce a mesenchymal-to-epithelial transition (MET) of the cultured cells. Islet-enriched pancreatic cells, allowed to dedifferentiate and expand in adherent cell culture, were transduced with an adenovirus containing KLF4 (Ad-Klf4). Cells were subsequently analysed for changes in cell morphology by light microscopy, and for the presence of epithelial and pancreatic markers by immunocytochemistry and quantitative RT/PCR. Infection with Ad-Klf4 resulted in morphological changes, down-regulation of mesenchymal markers, and re-expression of both epithelial and pancreatic cell markers including insulin and transcription factors specific to β-cells. This effect was further enhanced by culturing cells in suspension. However, the effects of Ad-KLf4 were transient and this was shown to be due to increased apoptosis in Klf4-expressing cells. Klf4 has been recently identified as a pioneer factor with the ability to modulate the structure of chromatin and enhance reprogramming/transdifferentiation. Our results show that Klf4 may have a role in the redifferentiation of expanded pancreatic cells in culture, but before this can be achieved the off-target effects that result in increased apoptosis would need to be overcome.
Congener patterns of the major organohalogen contaminant classes of PCBs, PBDEs and their metabolites and/or by-products (OH-PCBs, MeSO
2-PCBs, OH-PBDEs and MeO-PBDEs) were examined in adipose ...tissue, liver, brain and blood of East Greenland polar bears (
Ursus maritimus). PCB, OH-PCB, MeSO
2-PCB and PBDE congener patterns showed significant differences (
p
≤
0.05) mainly in the liver and the brain relative to the adipose tissue and the blood. OH-PBDEs and MeO-PBDEs were not detected in the brain and liver, but had different patterns in blood versus the adipose tissue. Novel OH-polybrominated biphenyls (OH-PBBs), one tri- and two tetra-brominated OH-PBBs were detected in all tissues and blood. Congener pattern differences among tissues and blood are likely due to a combination of factors, e.g., biotransformation and retention in the liver, retention in the blood and blood–brain barrier transport. Our findings suggest that different congener pattern exposures to these classes of contaminants should be considered with respect to potential target tissue-specific effects in East Greenland polar bears.
Tissues-specific (adipose tissue, liver, brain and blood) differences exist for the congener patterns of PCBs, PBDEs and their metabolites/degradation products in East Greenland polar bears.
The new layered compound Li3Ni2BiO6 has been prepared by a solid-state reaction. It crystallizes in the monoclinic C2/m space group; its lamellar structure is characterized by a honeycomb ordering ...between Ni2+ and Bi5+ within the slabs, while Li+ ions occupy octahedral sites in the interslab space. Stacking defects weakly alter the XRD pattern. By substitution of half of the nickel ions, the new phases Li3NiM′BiO6 (M′ = Mg, Cu, Zn) isostructural with Li3Ni2BiO6 have been synthesized under similar conditions. All these compounds demonstrate paramagnetic behavior at high temperature, and Li3Ni2BiO6 exhibits an antiferromagnetic ordering at 5.5 K. By topotactic molten salt ionic exchange, the new delafossite compound Ag3Ni2BiO6 has been also obtained and characterized.
Infarct volume (FIV) on follow-up diffusion-weighted imaging (FU-DWI) is only moderately associated with functional outcome in acute ischemic stroke patients. However, FU-DWI may contain other ...imaging biomarkers that could aid in improving outcome prediction models for acute ischemic stroke. We included FU-DWI data from the HERMES, ISLES, and MR CLEAN-NO IV databases. Lesions were segmented using a deep learning model trained on the HERMES and ISLES datasets. We assessed the performance of three classifiers in predicting functional independence for the MR CLEAN-NO IV trial cohort based on: (1) FIV alone, (2) the most important features obtained from a trained convolutional autoencoder (CAE), and (3) radiomics. Furthermore, we investigated feature importance in the radiomic-feature-based model. For outcome prediction, we included 206 patients: 144 scans were included in the training set, 21 in the validation set, and 41 in the test set. The classifiers that included the CAE and the radiomic features showed AUC values of 0.88 and 0.81, respectively, while the model based on FIV had an AUC of 0.79. This difference was not found to be statistically significant. Feature importance results showed that lesion intensity heterogeneity received more weight than lesion volume in outcome prediction. This study suggests that predictions of functional outcome should not be based on FIV alone and that FU-DWI images capture additional prognostic information.
PDF
