Multiplexed digital holography for fluid surface profilometry.

Digital holography (DH) has been widely used for imaging and characterization of microstructures and nanostructures in materials science and biology and also has the potential to provide high-resolution, nondestructive measurement of fluid surfaces. DH setups capture the complex wavefronts of light scattered by an object or reflected from a surface, allowing the quantitative measurements of their shape and deformation. However, their use in fluid profilometry is scarce and has not been explored in much depth to the best of our knowledge. We present an alternative use for a DH setup that can measure and monitor the surface of fluid samples. Based on DH reflectometry, our modeling shows that multiple reflections from the sample and the reference interfere and generate multiple holograms of the sample, resulting in a multiplexed image of the wavefront. The individual interferograms can be isolated in the spatial frequency domain, and the fluid surface can be digitally reconstructed from them. We further show that this setup can be used to track changes in the surface of a fluid over time, such as during the formation and propagation of waves or the evaporation of surface layers.

Coherent Phononics of van der Waals Layers on Nanogratings.

Strain engineering can be used to control the physical properties of two-dimensional van der Waals (2D-vdW) crystals. Coherent phonons, which carry dynamical strain, could push strain engineering to control classical and quantum phenomena in the unexplored picosecond temporal and nanometer spatial regimes. This intriguing approach requires the use of coherent GHz and sub-THz 2D phonons. Here, we report on nanostructures that combine nanometer thick vdW layers and nanogratings. Using an ultrafast pump-probe technique, we generate and detect in-plane coherent phonons with frequency up to 40 GHz and hybrid flexural phonons with frequency up to 10 GHz. The latter arises from the periodic modulation of the elastic coupling of the vdW layer at the grooves and ridges of the nanograting. This creates a new type of a tailorable 2D periodic phononic nanoobject, a flexural phononic crystal, offering exciting prospects for the ultrafast manipulation of states in 2D materials in emerging quantum technologies.

Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation.

AIMS: The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial allowed patients who completed the trial receiving their assigned dabigatran 150 mg (D150) or 110 mg (D110) twice a day to continue into the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. This permitted assessment of outcomes over a median of 4.6 and a maximum of 6.7 years, respectively. METHODS AND RESULTS: The analysed population included only those patients who completed RE-LY on dabigatran and continued into RELY-ABLE without interruption of assigned dabigatran. Cumulative risk was expressed as Kaplan-Meier plots. Outcomes were compared using Cox proportional hazard modelling. Stroke or systemic embolization rates were 1.25 and 1.54% per year (D150 and D110, respectively); hazard ratio (HR) 0.81 [95% confidence interval (CI): 0.68-0.96] (P = 0.02). Ischaemic stroke was 1.03 (D150) and 1.29%/year (D110); HR 0.79 (95% CI: 0.66-0.95) (P = 0.01). Haemorrhagic stroke rates were 0.11 (D150) and 0.13%/year (D110); HR 0.91 (95% CI: 0.51-1.62) (P = 0.75). Rates of major haemorrhage were 3.34 (D150) and 2.76%/year (D110); HR 1.22 (95% CI: 1.08-1.37) (P = 0.0008). Intracranial haemorrhage rates were 0.32 (D150) and 0.23%/year (D110); HR 1.37 (95% CI: 0.93-2.01) (P = 0.11). Mortality was 3.43 (D150) and 3.55%/year (D110); HR 0.97 (95% CI: 0.87-1.08) (P = 0.54). CONCLUSION: Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.

Risk of Venous Thromboembolism in Patients with Large Hemispheric Infarction Undergoing Decompressive Hemicraniectomy.

BACKGROUND: Deep-venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute ischemic stroke. This study is the first to examine the risk of venous thromboembolism in patients with large hemispheric infarction undergoing decompressive hemicraniectomy. METHODS: The study population included 95 consecutive patients with a large hemispheric infarction who underwent decompressive hemicraniectomy between 2006 and 2014 at our institution. All patients received prophylactic unfractionated heparin and intermittent compression devices (SCD). Patients were systematically screened for DVT at 5-day interval using Duplex ultrasound. PE was diagnosed on chest CT angiography. RESULTS: Mean age was 57 ± 12 years; mean BMI was 28.3 ± 7.4 kg/m(2). 30.5 % of patients had infarction in the dominant hemisphere and 69.5 % in the non-dominant hemisphere. The mean NIHSS score was 16.0 ± 5 at admission. The mean length of stay was 22 ± 17 days. 35 % of patients developed a DVT including 27 % who developed above-knee DVT and required placement of an inferior vena cava filter. In multivariable analysis, predictors of DVT were an NIHSS ≥ 17 (p = 0.007), seizures (p = 0.003), hypertension (p = 0.03), and increasing length of stay (p = 0.01). The proportion of patients who developed PE was 13 %. In multivariate analysis, BMI ≥ 30 predicted PE (p = 0.05). CONCLUSIONS: The rate of DVT and PE is remarkably high in patients with large hemispheric infarction undergoing decompressive hemicraniectomy despite prophylactic measures. We recommend routine screening for DVT in this population. Interventions beyond the standard prophylactic measures may be necessary in this high-risk group.

A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice.

Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr (-/-) mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr (-/-) Scarb1 (I179N) mice, respectively, when compared to gender-matched Ldlr (-/-) control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr (-/-) Scarb1 (I179N) mice compared to Ldlr (-/-) control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr (-/-) Scarb1 (I179N) mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis.

Coronary Artery Disease in Patients Undergoing Transvalvular Aortic Valve Implantation.

Coronary artery disease (CAD) is common in patients with severe aortic stenosis. With the advent of transcatheter aortic valve implantation (TAVI) as a therapeutic option, management of CAD in such patients has undergone a revolution. Younger patients are now candidates for treatment, and have a greater life-time probability of requiring post-TAVI coronary access. Considerations include pre-procedural assessment and revascularisation, procedural planning to avoid coronary obstruction as well as optimisation of post-procedural coronary access. The authors review the challenges of managing CAD in TAVI patients, shed light on the evidence base, and provide guidance on how to optimise management.

Large non-thermal contribution to picosecond strain pulse generation using the photo-induced phase transition in VO2.

Picosecond strain pulses are a versatile tool for investigation of mechanical properties of meso- and nano-scale objects with high temporal and spatial resolutions. Generation of such pulses is traditionally realized via ultrafast laser excitation of a light-to-strain transducer involving thermoelastic, deformation potential, or inverse piezoelectric effects. These approaches unavoidably lead to heat dissipation and a temperature rise, which can modify delicate specimens, like biological tissues, and ultimately destroy the transducer itself limiting the amplitude of generated picosecond strain. Here we propose a non-thermal mechanism for generating picosecond strain pulses via ultrafast photo-induced first-order phase transitions (PIPTs). We perform experiments on vanadium dioxide VO2 films, which exhibit a first-order PIPT accompanied by a lattice change. We demonstrate that during femtosecond optical excitation of VO2 the PIPT alone contributes to ultrafast expansion of this material as large as 0.45%, which is not accompanied by heat dissipation, and, for excitation density of 8 mJ cm-2, exceeds the contribution from thermoelastic effect by a factor of five.

High-speed modulation of a terahertz quantum cascade laser by coherent acoustic phonon pulses.

The fast modulation of lasers is a fundamental requirement for applications in optical communications, high-resolution spectroscopy and metrology. In the terahertz-frequency range, the quantum-cascade laser (QCL) is a high-power source with the potential for high-frequency modulation. However, conventional electronic modulation is limited fundamentally by parasitic device impedance, and so alternative physical processes must be exploited to modulate the QCL gain on ultrafast timescales. Here, we demonstrate an alternative mechanism to modulate the emission from a QCL device, whereby optically-generated acoustic phonon pulses are used to perturb the QCL bandstructure, enabling fast amplitude modulation that can be controlled using the QCL drive current or strain pulse amplitude, to a maximum modulation depth of 6% in our experiment. We show that this modulation can be explained using perturbation theory analysis. While the modulation rise-time was limited to ~800 ps by our measurement system, theoretical considerations suggest considerably faster modulation could be possible.

Sleep apnoea and cardiovascular outcomes after coronary artery bypass grafting.

OBJECTIVE: Patients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG. METHODS: This was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG. RESULTS: Among the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness. CONCLUSION: Sleep apnoea is independently associated with increased MACCE in patients undergoing CABG. TRIAL REGISTRATION NUMBER: NCT02701504.

High-Frequency Elastic Coupling at the Interface of van der Waals Nanolayers Imaged by Picosecond Ultrasonics.

Although the topography of van de Waals (vdW) layers and heterostructures can be imaged by scanning probe microscopy, high-frequency interface elastic properties are more difficult to assess. These can influence the stability, reliability, and performance of electronic devices that require uniform layers and interfaces. Here, we use picosecond ultrasonics to image these properties in vdW layers and heterostructures based on well-known exfoliable materials, i.e., InSe, hBN, and graphene. We reveal a strong, uniform elastic coupling between vdW layers over a wide range of frequencies of up to tens of gigahertz (GHz) and in-plane areas of 100 µm2. In contrast, the vdW layers can be weakly coupled to their supporting substrate, behaving effectively as free-standing membranes. Our data and analysis demonstrate that picosecond ultrasonics offers opportunities to probe the high-frequency elastic coupling of vdW nanolayers and image both "perfect" and "broken" interfaces between different materials over a wide frequency range, as required for future scientific and technological developments.

Concomitant Oral Anticoagulant and Nonsteroidal Anti-Inflammatory Drug Therapy in Patients With Atrial Fibrillation.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications that can potentially increase the risk of bleeding and thrombosis. OBJECTIVES: This study quantified the effect of NSAIDs in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial. METHODS: This was a post hoc analysis of NSAIDs in the RE-LY study, which compared dabigatran etexilate (DE) 150 and 110 mg twice daily (b.i.d.) with warfarin in patients with atrial fibrillation. Treatment-independent, multivariate-adjusted Cox regression analysis assessed clinical outcomes by comparing NSAID use with no NSAID use. Interaction analysis was obtained from treatment-dependent Cox regression modeling. Time-varying covariate analysis for NSAID use was applied to the Cox model. RESULTS: Among 18,113 patients in the RE-LY study, 2,279 patients used NSAIDs at least once during the trial. Major bleeding was significantly elevated with NSAID use (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.40 to 2.02; p < 0.0001). NSAID use did not significantly alter the risk of major bleeding for DE 150 or 110 mg b.i.d. relative to warfarin (pinteraction = 0.63 and 0.93, respectively). Gastrointestinal major bleeding was significantly elevated with NSAID use (HR: 1.81; 95% CI: 1.35 to 2.43; p < 0.0001). The rate of stroke or systemic embolism (stroke/SE) with NSAID use was significantly elevated (HR: 1.50; 95% CI: 1.12 to 2.01; p = 0.007). The use of NSAIDs did not significantly alter the relative efficacy on stroke/SE for DE 150 or 110 mg b.i.d. relative to warfarin (pinteraction = 0.59 and 0.54, respectively). Myocardial infarction rates were similar with NSAID use compared with no NSAID use (HR: 1.22; 95% CI: 0.77 to 1.93; p = 0.40). Patients were more frequently hospitalized if they used an NSAID (HR: 1.64; 95% CI: 1.51 to 1.77; p < 0.0001). CONCLUSIONS: The use of NSAIDs was associated with increased risk of major bleeding, stroke/SE, and hospitalization. The safety and efficacy of DE 150 and 110 mg b.i.d. relative to warfarin were not altered. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY]; NCT00262600).

Nanomechanical probing of the layer/substrate interface of an exfoliated InSe sheet on sapphire.

Van der Waals (vdW) layered crystals and heterostructures have attracted substantial interest for potential applications in a wide range of emerging technologies. An important, but often overlooked, consideration in the development of implementable devices is phonon transport through the structure interfaces. Here we report on the interface properties of exfoliated InSe on a sapphire substrate. We use a picosecond acoustic technique to probe the phonon resonances in the InSe vdW layered crystal. Analysis of the nanomechanics indicates that the InSe is mechanically decoupled from the substrate and thus presents an elastically imperfect interface. A high degree of phonon isolation at the interface points toward applications in thermoelectric devices, or the inclusion of an acoustic transition layer in device design. These findings demonstrate basic properties of layered structures and so illustrate the usefulness of nanomechanical probing in nanolayer/nanolayer or nanolayer/substrate interface tuning in vdW heterostructures.

Decompressive hemicraniectomy: predictors of functional outcome in patients with ischemic stroke.

OBJECT Patients presenting with large-territory ischemic strokes may develop intractable cerebral edema that puts them at risk of death unless intervention is performed. The purpose of this study was to identify predictors of outcome for decompressive hemicraniectomy (DH) in ischemic stroke. METHODS The authors conducted a retrospective electronic medical record review of 1624 patients from 2006 to 2014. Subjects were screened for DH secondary to ischemic stroke involving the middle cerebral artery, internal carotid artery, or both. Ninety-five individuals were identified. Univariate and multivariate analyses were performed for an array of clinical variables in relationship to functional outcome according to the modified Rankin Scale (mRS). Clinical outcome was assessed at 90 days and at the latest follow-up (mean duration 16.5 months). RESULTS The mean mRS score at 90 days and at the latest follow-up post-DH was 4. Good functional outcome was observed in 40% of patients at 90 days and in 48% of patient at the latest follow-up. The mortality rate at 90 days was 18% and at the last follow-up 20%. Univariate analysis identified a greater likelihood of poor functional outcome (mRS scores of 4-6) in patients with a history of stroke (OR 6.54 [95% CI1.39-30.66]; p = 0.017), peak midline shift (MLS) > 10 mm (OR 3.35 [95% CI 1.33-8.47]; p = 0.011), or a history of myocardial infarction (OR 8.95 [95% CI1.10-72.76]; p = 0.04). Multivariate analysis demonstrated elevated odds of poor functional outcome associated with a history of stroke (OR 9.14 [95% CI 1.78-47.05]; p = 0.008), MLS > 10 mm (OR 5.15 [95% CI 1.58-16.79; p = 0.007), a history of diabetes (OR 5.63 [95% CI 1.52-20.88]; p = 0.01), delayed time from onset of stroke to DH (OR 1.32 [95% CI 1.02-1.72]; p = 0.037), and evidence of pupillary dilation prior to DH (OR 4.19 [95% CI 1.06-16.51]; p = 0.04). Patients with infarction involving the dominant hemisphere had higher odds of unfavorable functional outcome at 90 days (OR 4.73 [95% CI 1.36-16.44]; p = 0.014), but at the latest follow-up, cerebral dominance was not significantly related to outcome (OR 1.63 [95% CI 0.61-4.34]; p = 0.328). CONCLUSIONS History of stroke, diabetes, myocardial infarction, peak MLS > 10 mm, increasing duration from onset of stroke to DH, and presence of pupillary dilation prior to intervention are associated with a worse functional outcome.

Coherent Acoustic Phonons in Colloidal Semiconductor Nanocrystal Superlattices.

The phonon properties of films fabricated from colloidal semiconductor nanocrystals play a major role in thermal conductance and electron scattering, which govern the principles for building colloidal-based electronics and optics including thermoelectric devices with a high ZT factor. The key point in understanding the phonon properties is to obtain the strength of the elastic bonds formed by organic ligands connecting the individual nanocrystallites. In the case of very weak bonding, the ligands become the bottleneck for phonon transport between infinitively rigid nanocrystals. In the opposite case of strong bonding, the colloids cannot be considered as infinitively rigid beads and the distortion of the superlattice caused by phonons includes the distortion of the colloids themselves. We use the picosecond acoustics technique to study the acoustic coherent phonons in superlattices of nanometer crystalline CdSe colloids. We observe the quantization of phonons with frequencies up to 30 GHz. The frequencies of quantized phonons depend on the thickness of the colloidal films and possess linear phonon dispersion. The measured speed of sound and corresponding wave modulus in the colloidal films point on the strong elastic coupling provided by organic ligands between colloidal nanocrystals.

Heterodyne mixing of millimetre electromagnetic waves and sub-THz sound in a semiconductor device.

We demonstrate heterodyne mixing of a 94 GHz millimetre wave photonic signal, supplied by a Gunn diode oscillator, with coherent acoustic waves of frequency ~100 GHz, generated by pulsed laser excitation of a semiconductor surface. The mixing takes place in a millimetre wave Schottky diode, and the intermediate frequency electrical signal is in the 1-12 GHz range. The mixing process preserves all the spectral content in the acoustic signal that falls within the intermediate frequency bandwidth. Therefore this technique may find application in high-frequency acoustic spectroscopy measurements, exploiting the nanometre wavelength of sub-THz sound. The result also points the way to exploiting acoustoelectric effects in photonic devices working at sub-THz and THz frequencies, which could provide functionalities at these frequencies, e.g. acoustic wave filtering, that are currently in widespread use at lower (GHz) frequencies.

Coherent phonon optics in a chip with an electrically controlled active device.

Phonon optics concerns operations with high-frequency acoustic waves in solid media in a similar way to how traditional optics operates with the light beams (i.e. photons). Phonon optics experiments with coherent terahertz and sub-terahertz phonons promise a revolution in various technical applications related to high-frequency acoustics, imaging, and heat transport. Previously, phonon optics used passive methods for manipulations with propagating phonon beams that did not enable their external control. Here we fabricate a phononic chip, which includes a generator of coherent monochromatic phonons with frequency 378 GHz, a sensitive coherent phonon detector, and an active layer: a doped semiconductor superlattice, with electrical contacts, inserted into the phonon propagation path. In the experiments, we demonstrate the modulation of the coherent phonon flux by an external electrical bias applied to the active layer. Phonon optics using external control broadens the spectrum of prospective applications of phononics on the nanometer scale.