High‐index dielectric subwavelength structures and metasurfaces are capable of enhancing light‐matter interaction by orders of magnitude via geometry‐dependent optical resonances. This enhancement, ...however, comes with a fundamental limitation of a narrow spectral range of operation in the vicinity of one or few resonant frequencies. Here, this limitation is tackled by introducing an innovative and practical approach to achieve spectrally tunable enhancement of light‐matter interaction with resonant metasurfaces. Resonance‐gradient metasurfaces are designed and fabricated with varying geometrical parameters that translate into resonant frequencies dependence on one of the coordinates of the metasurface. The metasurfaces are composed of bone‐like nanoresonators, which are made of germanium and support high‐quality optical resonances in the mid‐IR spectral range. The concept is applied to observe the resonant enhancement of the third and fifth harmonics generated from the gradient metasurfaces being used in conjunction with a tunable excitation laser to provide a wide spectral coverage of resonantly‐enhanced tunable generation of multiple optical harmonics.
Novel resonance‐gradient metasurfaces are designed and fabricated with varying geometrical parameters that translate into resonant frequencies dependence on one of the coordinates of the metasurface. This general concept is applied to observe the resonant enhancement of the third and fifth harmonics generated from the gradient metasurfaces being used in conjunction with a tunable excitation laser to provide a wide spectral coverage of resonantly‐enhanced tunable generation of multiple optical harmonics.
Surface‐enhanced infrared absorption spectroscopy (SEIRA) has emerged as a powerful technique for ultrasensitive chemical‐specific analysis. SEIRA can be realized by employing metasurfaces that can ...enhance light‐matter interactions in the spectral bands of molecular vibrations. Increasing sample complexity emphasizes the need for metasurfaces that can operate simultaneously at different spectral bands, both accessing rich spectral information over a broad band, and resolving subtle differences in the absorption fingerprints through narrow‐band resonances. Here, a novel concept of resonance‐gradient metasurfaces is introduced, where the required spectral selectivity is achieved via local high‐quality‐factor (high‐Q) resonances, while the continuous coverage of a broad band is enabled by the gradual adjustment of the unit‐cell dimensions along the planar structure. The highly tailorable design of the gradient metasurfaces provides flexibility for shaping the spectral sampling density to match the relevant bands of target analytes while keeping a compact device footprint. The versatility of the gradient metasurfaces is demonstrated through several sensing scenarios, including polymer mixture deconvolution, detecting a multistep bioassay, and identification of the onset of vibrational strong coupling regime. The proposed gradient‐resonance platform significantly contributes to the rapidly evolving landscape of nonlocal metasurfaces, enabling applications in molecular detection and analysis of fundamental light‐matter interaction phenomena.
Mid‐infrared all‐dielectric gradient metasurfaces, realized by gradually varying unit cell parameters along the structure, provide continuous tuning of high‐Q resonances over an ultra‐broad spectral range in a compact device footprint. The unmatched flexibility of such metasurfaces for SEIRA applications, including polymer mixture deconvolution, sensitive broadband biomolecule detection, and exploring the onset of vibrational strong coupling are demonstrated.
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Purpose: The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative‐free prostaglandin tafluprost (Taflotan®) in ...patients exhibiting ocular surface side‐effects during latanoprost (Xalatan®) treatment.
Methods: A total of 158 patients were enrolled in this open‐label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative‐free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break‐up time, Schirmer’s test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA‐DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits.
Results: Preservative‐free tafluprost maintained IOP at the same level after 12‐ weeks treatment (16.4 ± 2.7 mmHg) as latanoprost at baseline (16.8 ± 2.5 mmHg). During treatment with preservative‐free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer’s test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break‐up time improved significantly from 4.5 ± 2.5 seconds to 7.8 ± 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA‐DR and MUC5AC was also detected.
Conclusions: Preservative‐free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative‐free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.
Three dimensional (3D) nonlinear photonic crystals are one of the potential candidates for enabling photonic circuits. Most of the current top‐down fabrication approaches for such crystals are time ...consuming and suffer from small surface areas and limitations to specific substrates. Herein, a bottom‐up fabrication technique (UV‐soft nanoimprint lithography) together with solution processing of barium titanate (BaTiO3) nanoparticles is used to create large‐scale 3D nonlinear woodpile photonic crystals. Opposed to other 3D photonic crystals, the woodpile structure can be fabricated layer by layer. This property makes it suitable for roll‐to‐roll fabrication, which can be easily adapted in industry. The prepared photonic crystals with up to eight layers have surface areas of 1.0 cm2. The linear and nonlinear optical behavior of these 3D woodpile structures is characterized. Their transmission stop band lies around 757 nm and a relative linear minimum transmission of 48.4% for a four‐layer sample is obtained. Images of diffraction patterns together with polarization‐dependent second harmonic generation measurements prove a cubic photonic crystal structure in the linear and nonlinear regime. In addition to second‐order nonlinearity, BaTiO3 exhibits electro‐optic, elasto‐optic, and thermo‐optic effects. Therefore, it is especially suited for future active photonic crystal applications.
3D woodpile photonic crystals with surface areas of 1.0 cm2 in nonlinear BaTiO3 nanoparticles (NPs) are demonstrated. The fabrication method is UV‐soft nanoimprint lithography combined with solution processing of BaTiO3 NPs and a sol–gel precursor. The transmission stop band lies at around 757 nm, and a relative linear minimum transmission of 48.4% for a four‐layer sample is obtained.
We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other 3q26-related disorders reported thus ...far, we describe a phenotype with elevated platelet counts and dysmegakaryopoesis. The clinical course of our patient was complicated by symptomatic thrombophilia and chemoresistance. In addition, our case exhibited FLT3 (Fms-related tyrosine kinase 3) internal tandem duplication. Although anagrelide was successful in controlling elevated platelet counts, allogeneic stem cell transplantation failed to overcome chemoresistance due to simultaneous graft-versus-host-disease and relapse of acute myeloid leukemia. Given the dismal outcome of our case and previously reported cases, we propagate the implementation of targeted therapies to newly diagnosed patients with acute myeloid leukemia t(2;3). Preclinical models indicate drugs that plausibly target the EVI1-related molecular vulnerability as candidates for basket trials. Anagrelide exhibited a hopeful signal of activity in 3q26-related thrombocytosis and should be evaluated for implementation as supportive care.
Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of ...systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.).
The aim of this study was to examine the prevalence, distribution, and topographic relationship of vascular (18)F-sodium fluoride uptake and arterial calcification in major arteries.
Image data ...obtained from 75 patients undergoing whole-body (18)F-sodium fluoride PET/CT were evaluated retrospectively. Arterial radiotracer uptake and calcification were analyzed qualitatively and semiquantitatively.
(18)F-sodium fluoride uptake was observed at 254 sites in 57 (76%) of the 75 study patients, and calcification was observed at 1,930 sites in 63 (84%) of the patients. Colocalization of radiotracer accumulation and calcification could be observed in 223 areas of uptake (88%). However, only 12% of all arterial calcification sites showed increased radiotracer uptake.
Our data indicate the feasibility of (18)F-sodium fluoride PET/CT for the imaging of mineral deposition in arterial wall alterations. (18)F-sodium fluoride PET/CT may provide relevant information about the morphologic and functional properties of calcified plaque.
We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other 3q26-related disorders reported thus ...far, we describe a phenotype with elevated platelet counts and dysmegakaryopoesis. The clinical course of our patient was complicated by symptomatic thrombophilia and chemoresistance. In addition, our case exhibited FLT3 (Fms-related tyrosine kinase 3) internal tandem duplication. Although anagrelide was successful in controlling elevated platelet counts, allogeneic stem cell transplantation failed to overcome chemoresistance due to simultaneous graft-versus-host-disease and relapse of acute myeloid leukemia. Given the dismal outcome of our case and previously reported cases, we propagate the implementation of targeted therapies to newly diagnosed patients with acute myeloid leukemia t(2;3). Preclinical models indicate drugs that plausibly target the EVI1-related molecular vulnerability as candidates for basket trials. Anagrelide exhibited a hopeful signal of activity in 3q26-related thrombocytosis and should be evaluated for implementation as supportive care.
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