Influence of seed layers on the reflectance of sputtered aluminum thin films.

The fabrication of highly reflective aluminum coatings is still an important part of current research due to their high intrinsic reflectivity in a broad spectral range. By using thin seed layers of Cu, CuOx, Cr, CrOx, Au, and Ag, the morphology of sputtered (unprotected) aluminum layers and, consequently, their reflectance can be influenced. In this long-term study, the reflectance behavior was measured continuously using spectrophotometry. Particular seed layer materials enhance the reflectance of aluminum coatings significantly and reduce their long-term degradation. Combining such seed layers with evaporation processes and suitable protective layers could further increase the reflectance of aluminum coatings.

Structural, optical, and mechanical properties of TiO2 nanolaminates.

The structural, optical, and mechanical properties of TiO2 nanolaminate films grown by plasma-enhanced atomic layer deposition are discussed. Several TiO2/Al2O3 and TiO2/SiO2 compositions have been investigated to study the effect of the relative number of ALD oxide cycles on the film properties to obtain a high refractive index coating with low optical losses, low roughness, and low mechanical stress. The formation of crystalline TiO2 observed at high deposition temperature, or film thickness was inhibited by periodically introducing ultra-thin amorphous layers into the film. Only 4 ALD cycles of Al2O3 (corresponding to ca. 0.5 nm) between 335 ALD cycles of TiO2 (ca. 11 nm) form a closed, distinct layer suppressing the crystallization in TiO2 film. Consequently, the roughness of the pure TiO2 film is reduced from ca. 20 nm rms to 1 nm rms in the 335/4 nanolaminate, with only a slight decrease of the refractive index from 2.46 to 2.44 in 100 nm pure TiO2 and the nanolaminate, respectively. The refractive indices of the nanolaminates in various compositions vary between 2.38 and 2.50 at 632 nm, and the corresponding optical losses from the films are low. The mechanical stress was reduced to about 140 MPa in several TiO2/Al2O3 nanolaminates; however, lower mechanical stress has not been obtained with the studied compositions. The nanolaminate structure is preserved up to 600 °C annealing temperature. After annealing at 800 °C, the individual layers interdiffuse into each other so that no distinct nanolaminate structure is detected. By using TiO2/Al2O3 nanolaminates with reduced mechanical stress, a narrow bandpass filter was realized on various substrates, including half-ball and aspherical lenses.

A Low-Cost Beam-Scanning Second Harmonic Generation Microscope with Application for Agrochemical Development and Testing.

A low-cost second harmonic generation (SHG) microscope was constructed, and, for the first time, SHG microscopy was used for imaging agrochemical materials directly on the surface of common commercial crop leaves. The microscope uses a chromatically fixed (1560 nm) femtosecond fiber laser, a commercial 2D galvanometer mirror system, and a PCIe digital oscilloscope card, which together kept total instrument costs under $40 000 (USD), a significant decrease in cost and complexity from common systems (commercial and home-built) using tunable lasers and faster beam-scanning architectures. The figures of merit of the low-cost system still enabled a variety of measurements of agrochemical materials. Following confirmation of largely background-free SHG imaging of common crop leaves (soybean, maize, wheatgrass), SHG microscopy was used to image active ingredient crystallization after solution-phase deposition directly on the leaf surface, including at industrially relevant active ingredient concentrations (<0.05% w/w). Crystallization was also followed in real-time, with differences in crystallization time observed for different application procedures (spraying vs single droplet deposition). A strong dependency of active ingredient crystallization on the substrate was found, with an increased crystallization tendency observed on leaves vs on glass slides. Different crystal habits for the same active ingredient were also observed on different plant species. Finally, a model extended-release formulation was prepared, with a decrease in active ingredient crystallinity observed vs solution-phase deposition. These collective results demonstrate the need for making diagnostic measurements directly on the leaf surface and could help inform the next generation of pesticide products that ensure optimized agricultural output for a growing world population.

Recent Advances in Nonlinear Optical Analyses of Pharmaceutical Materials in the Solid State.

The past decade has seen an increase in the use of nonlinear optical (NLO) techniques such as second harmonic generation, coherent antistokes Raman scattering, stimulated Raman scattering, and two-photon fluorescence for the solid-state characterization of pharmaceutical materials. These combined techniques offer several advantages (e.g., speed, selectivity, quantitation) of potential interest to the pharmaceutical community, as decreased characterization times in formulation development and testing could help decrease the time required to bring new, higher quality drugs to market. The large body of literature recently published in this field merits a review. Literature will be discussed in order of drug development, starting with applications in initial therapeutic molecule crystallization and polymorphic analysis, followed by final dosage form characterization, and ending with drug product performance testing.

Imaging the Nonlinear Susceptibility Tensor of Collagen by Nonlinear Optical Stokes Ellipsometry.

Nonlinear optical Stokes ellipsometric (NOSE) microscopy was demonstrated for the analysis of collagen-rich biological tissues. NOSE is based on polarization-dependent second harmonic generation imaging. NOSE was used to access the molecular-level distribution of collagen fibril orientation relative to the local fiber axis at every position within the field of view. Fibril tilt-angle distribution was investigated by combining the NOSE measurements with ab initio calculations of the predicted molecular nonlinear optical response of a single collagen triple helix. The results were compared with results obtained previously by scanning electron microscopy, nuclear magnetic resonance imaging, and electron tomography. These results were enabled by first measuring the laboratory-frame Jones nonlinear susceptibility tensor, then extending to the local-frame tensor through pixel-by-pixel corrections based on local orientation.

Rapid Discrimination of Polymorphic Crystal Forms by Nonlinear Optical Stokes Ellipsometric Microscopy.

The use of nonlinear optical Stokes ellipsometric (NOSE) microscopy for rapid discrimination of two polymorphic forms of the small molecule d-mannitol is presented. Fast (8 MHz) polarization modulated beam-scanning microscopy and a recently developed iterative, nonlinear least-squares fitting algorithm were combined to allow discrimination of orthorhombic and monoclinic crystal structures of d-mannitol with data acquisition times of <7 s per field of view with a signal-to-noise ratio (SNR) of ∼300. Discrimination between polymorphic forms within the 99.99% confidence interval was achieved by standard statistical tests of the recovered probability density functions for the measured observables following two class linear discriminant analysis. These measurements target bottlenecks in small-volume, high-throughput solid form screening experiments for polymorph discovery in the development of emerging active pharmaceutical ingredients.

Parts per Million Powder X-ray Diffraction.

Here we demonstrate the use of second harmonic generation (SHG) microscopy-guided synchrotron powder X-ray diffraction (PXRD) for the detection of trace crystalline active pharmaceutical ingredients in a common polymer blend. The combined instrument is capable of detecting 100 ppm crystalline ritonavir in an amorphous hydroxypropyl methylcellulose matrix with a high signal-to-noise ratio (>5000). The high spatial resolution afforded by SHG microscopy allows for the use of a minibeam collimator to reduce the total volume of material probed by synchrotron PXRD. The reduction in probed volume results in reduced background from amorphous material. The ability to detect low crystalline loading has the potential to improve measurements in the formulation pipeline for pharmaceutical solid dispersions, for which even trace quantities of crystalline active ingredients can negatively impact the stability and bioavailability of the final drug product.

Finding the Needle in the Haystack: Characterization of Trace Crystallinity in a Commercial Formulation of Paclitaxel Protein-Bound Particles by Raman Spectroscopy Enabled by Second Harmonic Generation Microscopy.

Second harmonic generation (SHG) microscopy was used to rapidly identify regions of interest for localized confocal Raman spectroscopy measurements in order to quantify crystallinity within lyophilized Abraxane powder (protein bound paclitaxel for injectable suspension). Water insoluble noncentrosymmetric crystalline particles ranging from ∼1 to 120 µm were identified by SHG, with wide variability in crystal size and frequency observed between several batches of Abraxane. By targeting the Raman analysis to these localized regions identified by SHG, the required measurement time was decreased over 2 orders of magnitude, from 8 h to 2 s. Experimental Raman spectra of SHG active domains in Abraxane were in good agreement with experimental spectra of pure crystalline paclitaxel. These collective results are consistent with up to 30% of the active ingredient being present as poorly soluble crystalline particulates in some batches of Abraxane.

Digital deconvolution filter derived from linear discriminant analysis and application for multiphoton fluorescence microscopy.

A digital filter derived from linear discriminant analysis (LDA) is developed for recovering impulse responses in photon counting from a high speed photodetector (rise time of ~1 ns) and applied to remove ringing distortions from impedance mismatch in multiphoton fluorescence microscopy. Training of the digital filter was achieved by defining temporally coincident and noncoincident transients and identifying the projection within filter-space that best separated the two classes. Once trained, data analysis by digital filtering can be performed quickly. Assessment of the reliability of the approach was performed through comparisons of simulated voltage transients, in which the ground truth results were known a priori. The LDA filter was also found to recover deconvolved impulses for single photon counting from highly distorted ringing waveforms from an impedance mismatched photomultiplier tube. The LDA filter was successful in removing these ringing distortions from two-photon excited fluorescence micrographs and through data simulations was found to extend the dynamic range of photon counting by approximately 3 orders of magnitude through minimization of detector paralysis.

Polarization-modulated second harmonic generation ellipsometric microscopy at video rate.

Fast 8 MHz polarization modulation coupled with analytical modeling, fast beam-scanning, and synchronous digitization (SD) have enabled simultaneous nonlinear optical Stokes ellipsometry (NOSE) and polarized laser transmittance imaging with image acquisition rates up to video rate. In contrast to polarimetry, in which the polarization state of the exiting beam is recorded, NOSE enables recovery of the complex-valued Jones tensor of the sample that describes all polarization-dependent observables of the measurement. Every video-rate scan produces a set of 30 images (10 for each detector with three detectors operating in parallel), each of which corresponds to a different polarization-dependent result. Linear fitting of this image set contracts it down to a set of five parameters for each detector in second harmonic generation (SHG) and three parameters for the transmittance of the incident beam. These parameters can in turn be used to recover the Jones tensor elements of the sample. Following validation of the approach using z-cut quartz, NOSE microscopy was performed for microcrystals of both naproxen and glucose isomerase. When weighted by the measurement time, NOSE microscopy was found to provide a substantial (>7 decades) improvement in the signal-to-noise ratio relative to our previous measurements based on the rotation of optical elements and a 3-fold improvement relative to previous single-point NOSE approaches.

Transcranial Doppler emboli monitoring for stroke prevention after flow diverting stents.

OBJECTIVE: Flow diverting stents (FDS) are increasingly used for the treatment of intracranial aneurysms. While FDS can provide flow diversion of parent vessels, their high metal surface coverage can cause thromboembolism. Transcranial Doppler (TCD) emboli monitoring can be used to identify subclinical embolic phenomena after neurovascular procedures. Limited data exists regarding the use of TCDs for emboli monitoring in the periprocedural period after FDS placement. We evaluated the rate of positive TCDs microembolic signals and stroke after FDS deployment at our institution. METHODS: We retrospectively evaluated 105 patients who underwent FDS treatment between 2012 and 2016 using the Pipeline stent (Medtronic, Minneapolis, MN, USA). Patients were pretreated with aspirin and clopidogrel. All patients were therapeutic on clopidogrel pre-operatively. TCD emboli monitoring was performed immediately after the procedure. Microembolic signals (mES) were classified as "positive" (<15 mES/hour) and "strongly positive" (>15 mES/hour). Clinical stroke rates were determined at 2-week and 6-month post-operatively. RESULTS: A total of 132 intracranial aneurysms were treated in 105 patients. TCD emboli monitoring was "positive" in 11.4% (n=12) post-operatively and "strongly positive" in 4.8% (n=5). These positive cases were treated with heparin drips or modification of the antiplatelet regimen, and TCDs were repeated. Following medical management modifications, normalization of mES was achieved in 92% of cases. The overall stroke rates at 2-week and 6-months were 3.8% and 4.8%, respectively. CONCLUSIONS: TCD emboli monitoring may help early in the identification of thromboembolic events after flow diversion stenting. This allows for modification of medical therapy and, potentially, preventionf of escalation into post-operative strokes.

Atomically Thin Metal-Dielectric Heterostructures by Atomic Layer Deposition.

Heterostructures increasingly attracted attention over the past several years to enable various optoelectronic and photonic applications. In this work, atomically thin interfaces of Ir/Al2O3 heterostructures compatible with micro-optoelectronic technologies are reported. Their structural and optical properties were determined by spectroscopic and microscopic techniques (XRR, XPS, HRTEM, spectroscopic ellipsometry, and UV/vis/NIR spectrophotometry). The XRR and HRTEM analyses reveal a layer-by-layer growth mechanism of Ir in atomic scale heterostructures, which is different from the typical island-type growth of metals on dielectrics. Alongside, XPS investigations imply the formation of Ir-O-Al bonding at the interfaces for lower Ir concentrations, in contrast to the nanoparticle core-shell structure formation. Precisely tuning the ratio of the constituents ensures the control of the dispersion profile along with a transition from effective dielectric to metallic heterostructures. The Ir coating thickness was varied ranging from a few angstroms to films of about 7 nm in the heterostructures. The transition has been observed in the structures containing individual Ir coating thicknesses of about 2-4 nm. Following this, we show epsilon-near-zero metamaterials with tunable dielectric constants by precisely varying the composition of such heterostructures. Overall, a comprehensive study on structural and optical properties of the metal-dielectric interfaces of Ir/Al2O3 heterostructures was addressed, indicating an extension of the material portfolio available for novel optical functionalities.

A lesson in history: the evolution of endoscopic third ventriculostomy.

The history of endoscopic third ventriculostomy (ETV) demonstrates the importance of studying neurosurgery's history. A story that began with numerous technological advancements started to fizzle as neurosurgeons were stymied by problems encountered during the infancy of the technology they were still developing. The new technique, although sound in theory, failed to deliver a realistic solution for managing hydrocephalus; it lost the battle to the valved shunt. Over the last 15-20 years, a clearer understanding of pathophysiological mechanisms underlying various forms of hydrocephalus, along with effective implementation of evidence-based practice, has allowed for optimization of patient selection and a remarkable improvement in ETV success rates. Neurosurgeons would be wise to take the lessons learned in modernizing the ETV procedure and reassure themselves that these lessons do not apply to other methods that are tempting to dismiss as antiquated or archaic.

[Ibrutinib-associated atrial fibrillation : A therapeutic challenge]. / Fibrillation atriale associée à l'ibrutinib : un challenge thérapeutique.

Ibrutinib is a potent Bruton tyrosine kinase inhibitor and is an effective and well-tolerated treatment for a variety of lymphoid diseases. However, its use is associated with an increased incidence of atrial fibrillation ranging from 4% to 16%. New onset atrial fibrillation in cancer patients is associated with a significantly higher risk of heart failure and thromboembolism, even after adjusting for known risk factors. Ibrutinib also inhibits platelet activation and decisions regarding anticoagulation must be carefully weighed against this increased risk of bleeding. It is well-known that the anti-arrhythmic and antithrombotic strategy for atrial fibrillation related to ibrutinib has its own characteristics. Physicians should be familiar with the special management considerations imposed by this drug. Indeed, the co-prescription of therapy in combination with ibrutinib must be carefully weighed in view of its numerous drug interactions. We review the potential mechanisms and incidence of ibrutinib-associated atrial fibrillation.

Plasma-Enhanced Atomic Layer Deposition of HfO2 with Substrate Biasing: Thin Films for High-Reflective Mirrors.

Tuning ion energies in plasma-enhanced atomic layer deposition (PEALD) processes enables fine control over the material properties of functional coatings. The growth, structural, mechanical, and optical properties of HfO2 thin films are presented in detail toward photonic applications. The influence of the film thickness and bias value on the properties of HfO2 thin films deposited at 100 °C using tetrakis(dimethylamino)hafnium (TDMAH) and oxygen plasma using substrate biasing is systematically analyzed. The HfO2 films deposited without a substrate bias show an amorphous microstructure with a low density, low refractive index, high incorporation of residual hydroxyl (OH) content, and high residual tensile stress. The material properties of HfO2 films significantly improved at a low bias voltage due to the interaction with oxygen ions accelerated to the film. Such HfO2 films have a higher density, higher refractive index, and lower residual OH incorporation than films without bias. The mechanical stress becomes compressive depending on the bias values. Further increasing the ion energies by applying a larger substrate bias results in a decrease of the film density, refractive index, and a higher residual OH incorporation as well as crystalline inclusions. The comparable material properties of the HfO2 films have been reported using tris(dimethylamino)cyclopentadienyl hafnium (TDMACpH) in a different apparatus, indicating that this approach can be transferred to various systems and is highly versatile. Finally, the substrate biasing technique has been introduced to deposit stress-compensated, crack- and delamination-free high-reflective (HR) mirrors at 355 and 532 nm wavelengths using HfO2 and SiO2 as high and low refractive index materials, respectively. Such mirrors could not be obtained without the substrate biasing during the deposition because of the high tensile stress of HfO2, leading to cracks in thick multilayer systems. An HR mirror for 532 nm wavelength shows a high reflectance of 99.93%, a residual transmittance of ∼530 ppm, and a low absorption of ∼11 ppm, as well as low scattering losses of ∼4 ppm, high laser-induced damage threshold, low mechanical stress, and high environmental stability.

Optical bandgap control in Al2O3/TiO2 heterostructures by plasma enhanced atomic layer deposition: Toward quantizing structures and tailored binary oxides.

Atomically thin heterostructures and superlattices are promising candidates for various optoelectronic and photonic applications. Different combinations of Al2O3/TiO2 composites are obtained by plasma enhanced atomic layer deposition (PEALD). Their growth, composition, dispersion relation, and optical bandgap are systematically studied by means of UV/VIS spectrophotometry, spectroscopic ellipsometry (SE), x-ray reflectometry (XRR), scanning transmission electron microscopy(STEM) and x-ray photoelectron spectroscopy (XPS). Besides, an effective medium approximation (EMA) approach is applied to model the heterostructures theoretically. The refractive index and the indirect bandgap of the heterostructures depend on the ratio of the two oxides, while the bandgap is very sensitive to the thicknesses of the barrier and quantum well layers. A large blue shift of the absorption edge from 400 nm to 320 nm is obtained by changing the TiO2 (quantum well) thickness from ~2 nm to ~0.1 nm separated by ~2 nm of Al2O3 (barrier) layers. PEALD unfolds the possibility of achieving optical quantizing effects within complex heterostructures enabling control of their structures down to atomic scale. It enables a path towards atomic scale processing of new 'artificial' materials with desired refractive indices and bandgap combinations by precise control of their compositions.

Epidemiological, clinical, and echocardiographic features of twenty 'Takotsubo-like' reversible myocardial dysfunction cases with normal coronarography following immersion pulmonary oedema.

BACKGROUND: Pulmonary immersion oedema is a frequent diving accident. Although its outcome is generally favourable within 72 h, it can nonetheless lead to heart failure or sudden death. Cases of transient myocardial dysfunction have been reported in the literature. This phenomenon is similar to Takotsubo syndrome in many ways. It is characterised by transient myocardial hypokinesia, without associated coronary lesions. METHODS: We report on 20 cases of patients who showed transient alteration of left ventricular kinetics with normal coronary angiography over the course of an immersion pulmonary oedema. RESULTS: The echocardiographic localisation of the myocardial damage was generally focal and not centred on the apex with an average left ventricular ejection fraction of 45%. The main anomalies in the electrocardiographic repolarisation were T wave inversion with corrected QT interval prolongation. We also observed a moderate increase in troponin levels, with discordance between the enzymatic peak and the severity of the left ventricle segmental dysfunction. CONCLUSION: These cases suggest the incidence of a clinical entity strongly reminiscent of Takotsubo phenomenon of atypical topography as a consequence of diving accidents.

Wafer-level integration of self-aligned high aspect ratio silicon 3D structures using the MACE method with Au, Pd, Pt, Cu, and Ir.

The wafer-level integration of high aspect ratio silicon nanostructures is an essential part of the fabrication of nanodevices. Metal-assisted chemical etching (MACE) is a promising low-cost and high-volume technique for the generation of vertically aligned silicon nanowires. Noble metal nanoparticles were used to locally etch the silicon substrate. This work demonstrates a bottom-up self-assembly approach for noble metal nanoparticle formation and the subsequent silicon wet etching. The macroscopic wafer patterning has been done by using a poly(methyl methacrylate) masking layer. Different metals (Au, Pt, Pd, Cu, and Ir) were investigated to derive a set of technologies as platform for specific applications. Especially, the shape of the 3D structures and the resulting reflectance have been investigated. The Si nanostructures fabricated using Au nanoparticles show a perfect light absorption with a reflectance below 0.3%. The demonstrated technology can be integrated into common fabrication processes for microelectromechanical systems.

Internal Thoracic Artery to Vertebral Artery Bypass Surgery: A Cadaveric Feasibility Study.

OBJECTIVE: Posterior circulation strokes account for over one quarter of all ischemic strokes. The frequency of vertebral artery origin stenosis (VAOS) in patients with vertebrobasilar insufficiency (VBI) has been estimated to be as high 26%-32%, and VAOS is the direct cause of posterior circulation strokes in 9% of patients. This association could have a significant genetic component. This study examines the feasibility of the internal thoracic artery (ITA) as a donor vessel for revascularization in patients with VAOS. METHODS: Ten sides from 5 fresh-frozen white cadaveric necks derived from 3 women and 2 men were used in this study. The mean age of the cadavers at death was 77.2 years (range, 68-88 years). The subclavian artery, vertebral artery, and ITA were dissected. The length and diameter (proximal and distal) of the V1 segment and the length and diameter of the ITA were recorded. Finally, the ITA was transposed to the V1 segment of the vertebral artery (VA1). RESULTS: The mean length of the VA1 and its diameter at the proximal and distal parts were 35.51 and 3.69 mm, respectively. The mean length and diameter of the ITA were 26.53 and 3.27 mm, respectively. Rerouting the ITA to the VA1 was feasible without tension on all sides. CONCLUSIONS: This study indicates that the ITA is anatomically and hemodynamically an excellent option for bypass surgery in a VAOS scenario. We present convincing and reproducible data to aid neurosurgeons in choosing the procedure best suited to their patients.

A randomized crossover-design study to investigate the plaque removal efficacy of two power toothbrushes: Philips Sonicare Flexcare and Oral-B Triumph.

The Sonicare FlexCare and the Oral-B Triumph Professional Care 9000 power toothbrushes were compared in a single-use, examiner-masked, crossover clinical trial. Outcomes were evaluated using the Turesky Modified Quigley-Hein (TMQH) plaque index. Percent reduction in overall plaque score because of toothbrushing was the primary efficacy measure. Subjects were required to have a TMQH score > or = 1.8 at screening after refraining from oral hygiene for 24 hours. The study included three visits. At visit 1, subjects were randomized to one of two treatment sequences, given their first toothbrush and toothpaste, and instructed to use them twice daily for 2 minutes during a 1-week familiarization phase. Before visit 2, subjects again refrained from oral hygiene for 24 hours. At this visit, plaque scores were assessed before and after a 2-minute supervised brushing episode, then the second test product was issued. Familiarization, plaque accumulation, and clinical examinations were the same for both product use periods. Data were analyzed using a linear mixed effects model with subject as a grouping factor. Treatment effects were expressed as mean values and the appropriate 95% confidence intervals (CI). Ninety-six subjects were screened with 93 subjects completing the study. The sample's TMQH score at Visit 1 was 3.18 +/- 0.42 (mean +/- standard deviation [SD]). Full-mouth prebrushing plaque scores were 2.85 +/- 0.49 for FlexCare and 2.94 +/- 0.45 for Triumph. Respective full-mouth reductions in overall plaque score were 38.02% +/- 15.14% and 30.43% +/- 14.05%. The estimated treatment effect, expressed as difference between FlexCare and Triumph in percent plaque index reduction, was 7.59% with a 95% CI from 4.79% to 10.40%. Similar differences were observed for all subregions, including anterior, posterior, interproximal, and interproximal posterior sites. The same protocol design was used at an earlier study in another center. The combined overall treatment effect from the two studies was estimated at 6.97% (95% CI: 5.17%, 8.78%), favoring FlexCare.