Due to their low surface mass density, two-dimensional materials with a strong piezoelectric response are interesting for nanoelectromechanical systems with high force sensitivity. Unlike graphene, ...the two sublattices in a monolayer of hexagonal boron nitride (hBN) are occupied by different elements, which breaks inversion symmetry and allows for piezoelectricity. This has been confirmed with density functional theory calculations of the piezoelectric constant of hBN. Here, we formulate an entirely analytical derivation of the electronic contribution to the piezoelectric response in this system based on the concepts of strain-induced pseudomagnetic vector potential and the modern theory of polarization that relates the polar moment to the Berry curvature. Our findings agree with the symmetry restrictions expected for the hBN lattice and reproduce well the magnitude of the piezoelectric effect previously obtained ab initio.
Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called ...the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD.
We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant.
Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%–36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion.
In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.
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The photon-like behavior of electrons in graphene causes unusual confinement properties that depend strongly on the geometry and strength of the surrounding potential. We report bottom-up synthesis ...of atomically-precise one-dimensional (1D) arrays of point charges on graphene that allow exploration of a new type of supercritical confinement of graphene carriers. The arrays were synthesized by arranging F
TCNQ molecules into a 1D lattice on back-gated graphene, allowing precise tuning of both the molecular charge and the array periodicity. While dilute arrays of ionized F
TCNQ molecules are seen to behave like isolated subcritical charges, dense arrays show emergent supercriticality. In contrast to compact supercritical clusters, these extended arrays display both supercritical and subcritical characteristics and belong to a new physical regime termed "frustrated supercritical collapse". Here carriers in the far-field are attracted by a supercritical charge distribution, but their fall to the center is frustrated by subcritical potentials in the near-field, similar to trapping of light by a dense cluster of stars in general relativity.
To address the robustness of the transport gap induced by locally strained regions in graphene nanostructures, the effect of disorder and smoothness of the interface region is investigated within the ...Landauer-Buttiker formalism. The electronic conductance across strained junctions and barriers in graphene nanoribbons is calculated numerically, with and without various types of disorder, and comparing smooth and sharp strain junctions. A smooth strain barrier in graphene is seen to be generically as efficient in suppressing transport at low densities as a sharp one, and the critical density (or energy) for the onset of transmission depends on the strain orientation with respect to the ribbon. In addition, hopping (or strain) inhomogeneity and work function mismatch at the interface region do not visibly degrade the transport gap. These results show that the strain-induced transport gap at a strain junction is robust to more realistic strain conditions.
Computational fluid dynamics (CFD) of cerebral venous flows has become popular owing to the possibility of using local hemodynamics and hemoacoustics to help diagnose and plan treatments for venous ...diseases of the brain. Lumen geometries in low-pressure cerebral veins are different from those in cerebral arteries, often exhibiting fenestrations and flattened or triangular cross section, in addition to constrictions and expansions. These can challenge conventional size-based volume meshing strategies, and the ability to resolve nonlaminar flows. Here we present a novel strategy leveraging estimation of length scales that could be present if flow were to become transitional or turbulent. Starting from the lumen geometry and flow rate boundary conditions, centerlines are used to determine local hydraulic diameters and cross-sectional mean velocities, from which flow length scales are approximated using conventional definitions of local Kolmogorov and Taylor microscales. By inspection of these scales, a user specifies minimum and maximum mesh edge lengths, which are then distributed along the model in proportion to the approximated local Taylor length scales. We demonstrate in three representative cases that this strategy avoids some of the pitfalls of conventional size-based strategies. An exemplary CFD mesh-refinement study shows convergence of high-frequency flow instabilities even starting from relatively coarse edge lengths near the lower bounds of the approximated Taylor length scales. Rational consideration of the length scales in a possibly nonlaminar flow may thus provide a useful and replicable baseline for denovo meshing of complicated or unfamiliar venous lumen geometries.
The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic ...perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI).
Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP.
MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital (
=0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group (
=0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI Thrombolysis in Cerebral Infarction score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI,
=0.02; CTP,
=0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups.
Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.
The details of the superconducting to quantum metal transition (SQMT) at T = 0 are an open problem that invokes great interest in the nature of this exotic and unexpected ground state (Ephron et al., ...1996; Mason and Kapitulnik, 1999; Chervenak and Valles, 2000). However, the SQMT was not yet investigated in a crystalline 2D superconductor with coexisting and fluctuating quantum orders. Here, we report the observation of a SQMT in 2D ion-gel-gated 1T-TiSe2 (Li et al., 2016) driven by a magnetic field. A field-induced crossover between Bose quantum metal and vortex quantum creeping with an increasing field is observed. We discuss the interplay between superconducting and CDW fluctuations (discommensurations) and their relation to the anomalous quantum metal (AQM) phase. From our findings, gate-tunable 1T-TiSe2 emerges as a privileged platform to scrutinize, in a controlled way, the details of the SQMT, the role of coexisting fluctuating orders and, ultimately, to obtain a deeper understanding of the fate of superconductivity in strictly two-dimensional crystals near zero temperature.
Performing mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based.
To compare patients' outcome, relative merits of achieving recanalization, and ...predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT.
In the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms.
MT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 - 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 - 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO.
In selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR.
NCT03496064.
Imaging findings can predict outcomes in patients with acute stroke. Relationships between imaging findings and clinical and imaging outcomes in patients randomized to intravenous tissue-type ...plasminogen activator-alone versus tissue-type plasminogen activator plus endovascular therapy (Solitaire device) in the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) study were assessed.
We evaluated associations between imaging assessments (baseline mismatch profiles/ischemic core volumes and successful reperfusion) with imaging outcomes (27-hour infarct volume/growth) and clinical outcomes (modified Rankin Scale scores at 90 days). Imaging variables that predict favorable clinical outcomes were assessed in both univariate and multivariate models.
One hundred and ninety-five patients were included. Successful reperfusion and infarct volume (assessed at 27 hours) were powerful independent predictors of favorable clinical outcomes (modified Rankin Scale score of 0-2 at 90 days). Patients with the target mismatch profile at baseline had a higher rate of reperfusion, lesser infarct growth, smaller infarct volumes, and better clinical outcomes in the Solitaire plus tissue-type plasminogen activator (intervention) group than those in the tissue-type plasminogen activator-alone (control) group. Patients with larger mismatch volumes at baseline had a trend toward better treatment response in the intervention group than patients who had smaller (<50 mL) mismatch volumes.
Patients who achieved reperfusion had substantially more favorable clinical and imaging outcomes in both the intervention and the control groups. Infarct volume at 27 hours strongly correlated with clinical outcome at 90 days in both treatment groups. SWIFT PRIME patients with the target mismatch profile had a highly favorable response to endovascular therapy on both clinical and imaging outcomes. Both reperfusion and infarct volumes at 27 hours were powerful and independent predictors of 90-day clinical outcomes.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.
•A deep neural network can construct plausible cohorts of aneurysm geometries.•Sac-average wall shear stress may share too much mutual information with geometry.•Conversely, some metrics of complex ...flow may be too sensitive to geometry.
Vessel geometry and hemodynamics are intrinsically linked, whereby geometry determines hemodynamics, and hemodynamics influence vascular remodeling. Both have been used for testing clinical outcomes, but geometry/morphology generally has less uncertainty than hemodynamics derived from medical image-based computational fluid dynamics (CFD). To provide clinical utility, CFD-based hemodynamic parameters must be robust to modeling errors and/or uncertainties, but must also provide useful information not more-easily extracted from shape alone. The objective of this study was to methodically assess the response of hemodynamic parameters to gradual changes in shape created using an unsupervised 3D shape interpolation method.
We trained the neural network NeuroMorph on 3 patient-derived intracranial aneurysm surfaces (labelled A, B, C), and then generated 3 distinct morph sequences (A→B, B→C, C→A) each containing 10 interpolated surfaces. From high-fidelity CFD simulation of these, we calculated a variety of common reduced hemodynamic parameters, including many previously associated with aneurysm rupture, and analyzed their responses to changes in shape, and their correlations.
The interpolated surfaces demonstrate complex, gradual changes in branch angles, vessel diameters, and aneurysm morphology. CFD simulation showed gradual changes in aneurysm jetting characteristics and wall-shear stress (WSS) patterns, but demonstrated a range of responses from the reduced hemodynamic parameters. Spatially and temporally averaged parameters including time-averaged WSS, time-averaged velocity, and low-shear area (LSA) showed low variation across all morph sequences, while parameters of flow complexity such as oscillatory shear, spectral broadening, and spectral bandedness indices showed high variation between slightly-altered neighboring surfaces. Correlation analysis revealed a great deal of mutual information with easier-to-measure shape-based parameters.
In the absence of large clinical datasets, unsupervised shape interpolation provides an ideal laboratory for exploring the delicate balance between robustness and sensitivity of nominal hemodynamic predictors of aneurysm rupture. Parameters like time-averaged WSS and LSA that are highly “robust” may, as a result, be effectively redundant to morphological predictors, whereas more sensitive parameters may be too uncertain for practical clinical use. Understanding these sensitivities may help identify parameters that are capable of providing added value to rupture risk assessment.
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