Efficacy and safety of in-hospital treatment of Covid-19 infection with low-dose hydroxychloroquine and azithromycin in hospitalized patients: A retrospective controlled cohort study.

Objectives: In this study we evaluate the efficacy and safety of a treatment protocol with standard dose of hydroxychloroquine plus azithromycin in patients hospitalized with COVID-19 infection. Methods: We conducted a retrospective analysis to compare the 28-day mortality rate in 352 patients treated with hydroxychloroquine with or without azithromycin (HCQ-group) in our hospital with a contemporary control group of 3533 patients receiving standard of care from the Belgian Collaborative Group on COVID-19 Hospital Surveillance. Results: All patients who received at least one dose of treatment were included in the analysis. A statistically significant reduction in crude mortality rate at 28 days was observed in the HCQ-group compared to standard of care (16.8% vs 25.9%,p â€‹= â€‹0.001).Patients in the treatment group were on average younger (69,7 vs73,1 years, p â€‹= â€‹0,0002), were less likely to smoke or to have malignancy and more likely to be male. Patients in the treatment group were more likely to be obese, immunocompromised or to have arterial hypertension, liver disease and lung disease.After adjustment for these variables the OR for mortality was 0.635 (95%CI 0.464-0.875). Patients who did not receive HCQ had a 57% higher risk of mortality. A survival benefit in the treatment group was consistent across all age groups. 13 patients discontinued treatment due to side effects (4 with QTc-prolongation>60msec (1.1%) and 9 because of gastro-intestinal symptoms (2.55%)). No episodes of ventricular arrhythmia or torsade de pointes were recorded during treatment. Conclusion: Treatment of COVID-19 using a combination of hydroxychloroquine plus azithromycin was safe and was associated with a statistically significant mortality benefit in the treatment of COVID-19 infection in hospitalized patients. Our findings do not support the current negative recommendations regarding this treatment.

Intensity Modulated Proton Therapy for Bilateral Breast or Chest Wall and Comprehensive Nodal Irradiation for Synchronous Bilateral Breast Cancer: Initial Clinical Experience and Dosimetric Comparison.

Purpose: Synchronous bilateral breast cancer (SBBC) poses distinct challenges for radiation therapy planning. We report our proton therapy experience in treating patients with SBBC. We also provide a dosimetric comparison of intensity modulated proton therapy (IMPT) versus photon therapy. Methods and Materials: Patients with SBBC who received IMPT at our institution were retrospectively analyzed. The clinical target volume (CTV) included the breast or chest wall and comprehensive regional lymph nodes, including axilla, supraclavicular fossa, and the internal mammary chain. Intensity modulated proton therapy and volumetric modulated arc therapy (VMAT) plans were generated with the goal that 90% of the CTV would recieve at least 90% of the prescription dose (D90>=90%). Comparisons between modalities were made using the Wilcoxon signed rank test. Physician-reported acute toxic effects and photography were collected at baseline, end of treatment, and each follow-up visit. Results: Between 2015 and 2018, 11 patients with SBBC were treated with IMPT. The prescription was 50 Gy in 25 fractions. The median CTV D90 was 99.9% for IMPT and 97.6% for VMAT (P = .001). The mean heart dose was 0.7 Gy versus 7.2 Gy (P = .001), the total lung mean dose was 7.8 Gy versus 17.3 Gy (P = .001), and the total lung volume recieving 20 Gy was 13.0% versus 27.4% (P = .001). The most common acute toxic effects were dermatitis (mostly grade 1-2 with 1 case of grade 3) and grade 1 to 2 fatigue. The most common toxic effects at the last-follow up (median, 32 months) were grade 1 skin hyperpigmentation, superficial fibrosis, and extremity lymphedema. No nondermatologic or nonfatigue adverse events of grade >1 were recorded. Conclusions: Bilateral breast and/or chest wall and comprehensive nodal IMPT is technically feasible and associated with low rates of severe acute toxic effects. Treatment with IMPT offered improved target coverage and normal-tissue sparing compared with photon therapy. Long-term follow-up is ongoing to assess efficacy and toxic effects.

Subwavelength hybrid plasmonic structures for nonlinear nanophotonics.

Plasmonic structures made of a semiconductor-insulator-metal hybrid provide efficient routes for second-harmonic and sum-frequency generation in sub-micrometer structures, which ultimately may boost on-chip integrated plasmonic circuits.

Advanced Optical Programming of Individual Meta-Atoms Beyond the Effective Medium Approach.

Nanometer-thick active metasurfaces (MSs) based on phase-change materials (PCMs) enable compact photonic components, offering adjustable functionalities for the manipulation of light, such as polarization filtering, lensing, and beam steering. Commonly, they feature multiple operation states by switching the whole PCM fully between two states of drastically different optical properties. Intermediate states of the PCM are also exploited to obtain gradual resonance shifts, which are usually uniform over the whole MS and described by effective medium response. For programmable MSs, however, the ability to selectively address and switch the PCM in individual meta-atoms is required. Here, simultaneous control of size, position, and crystallization depth of the switched phase-change material (PCM) volume within each meta-atom in a proof-of-principle MS consisting of a PCM-covered Al-nanorod antenna array is demonstrated. By modifying optical properties locally, amplitude and light phase can be programmed at the meta-atom scale. As this goes beyond previous effective medium concepts, it will enable small adaptive corrections to external aberrations and fabrication errors or multiple complex functionalities programmable on the same MS.

Highly Confined and Switchable Mid-Infrared Surface Phonon Polariton Resonances of Planar Circular Cavities with a Phase Change Material.

Mid-infrared (MIR) photonics demands highly confined optical fields to obtain efficient interaction between long-wavelength light and nanomaterials. Surface polaritons excited on polar semiconductor and metallic material interfaces exhibit near-fields localized on subwavelength scales. However, realizing a stronger field concentration in a cavity with a high quality ( Q) factor and a small mode volume is still challenging in the MIR region. This study reports MIR field concentration of surface phonon polaritons (SPhPs) using planar circular cavities with a high Q factor of ∼150. The cavities are fabricated on a thin film of the phase change material Ge3Sb2Te6 (GST) deposited on a silicon carbide (SiC) substrate. Scattering-type scanning near-field optical microscopy visualizes the near-field distribution on the samples and confirms directly that the SPhP field is strongly concentrated at the center of the centrosymmetric cavities. The smallest concentrated field size is 220 nm in diameter which corresponds to 1/50 of the wavelength of the incident light that is far below the diffraction limit. The thin GST film enhances the SPhP confinement, and it is used to switch the confinement off by tuning the cavity resonance induced by the phase change from the amorphous to the crystalline phase. This subwavelength and switchable field concentration within a high- Q polariton cavity has the potential to greatly enhance the light-matter interaction for molecular sensing and emission enhancement in MIR systems.

Reversible optical switching of highly confined phonon-polaritons with an ultrathin phase-change material.

Surface phonon-polaritons (SPhPs), collective excitations of photons coupled with phonons in polar crystals, enable strong light-matter interaction and numerous infrared nanophotonic applications. However, as the lattice vibrations are determined by the crystal structure, the dynamical control of SPhPs remains challenging. Here, we realize the all-optical, non-volatile, and reversible switching of SPhPs by controlling the structural phase of a phase-change material (PCM) employed as a switchable dielectric environment. We experimentally demonstrate optical switching of an ultrathin PCM film (down to 7 nm, <λ/1,200) with single laser pulses and detect ultra-confined SPhPs (polariton wavevector kp > 70k0, k0 = 2π/λ) in quartz. Our proof of concept allows the preparation of all-dielectric, rewritable SPhP resonators without the need for complex fabrication methods. With optimized materials and parallelized optical addressing we foresee application potential for switchable infrared nanophotonic elements, for example, imaging elements such as superlenses and hyperlenses, as well as reconfigurable metasurfaces and sensors.

Diffusive Motion of Linear Microgel Assemblies in Solution.

Due to the ability of microgels to rapidly contract and expand in response to external stimuli, assemblies of interconnected microgels are promising for actuation applications, e.g., as contracting fibers for artificial muscles. Among the properties determining the suitability of microgel assemblies for actuation are mechanical parameters such as bending stiffness and mobility. Here, we study the properties of linear, one-dimensional chains of poly(N-vinylcaprolactam) microgels dispersed in water. They were fabricated by utilizing wrinkled surfaces as templates and UV-cross-linking the microgels. We image the shapes of the chains on surfaces and in solution using atomic force microscopy (AFM) and fluorescence microscopy, respectively. In solution, the chains are observed to execute translational and rotational diffusive motions. Evaluation of the motions yields translational and rotational diffusion coefficients and, from the translational diffusion coefficient, the chain mobility. The microgel chains show no perceptible bending, which yields a lower limit on their bending stiffness.

Extreme ultraviolet proximity lithography for fast, flexible and parallel fabrication of infrared antennas.

We present a method for fabrication of large arrays of nano-antennas using extreme-ultraviolet (EUV) illumination. A discharge-produced plasma source generating EUV radiation around 10.88 nm wavelength is used for the illumination of a photoresist via a mask in a proximity printing setup. The method of metallic nanoantennas fabrication utilizes a bilayer photoresist and employs a lift-off process. The impact of Fresnel-diffraction of EUV light in the mask on a shape of the nanostructures has been investigated. It is shown how by the use of the same rectangular apertures in the transmission mask, antennas of various shapes can be fabricated. Using Fourier transform infrared spectroscopy, spectra of antennas reflectivity were measured and compared to FDTD simulations demonstrating good agreement.

A Switchable Mid-Infrared Plasmonic Perfect Absorber with Multispectral Thermal Imaging Capability.

A switchable perfect absorber with multispectral thermal imaging capability is presented. Aluminum nanoantenna arrays above a germanium antimony telluride (GST) spacer layer and aluminum mirror provide efficient wavelength-tunable absorption in the mid-infrared. Utilizing the amorphous-to-crystalline phase transition in GST, this device offers switchable absorption with strong reflectance contrast at resonance and large phase-change-induced spectral shifts.

Active Chiral Plasmonics.

Active control over the handedness of a chiral metamaterial has the potential to serve as key element for highly integrated polarization engineering approaches, polarization sensitive imaging devices, and stereo display technologies. However, this is hard to achieve as it seemingly involves the reconfiguration of the metamolecule from a left-handed into a right-handed enantiomer and vice versa. This type of mechanical actuation is intricate and usually neither monolithically realizable nor viable for high-speed applications. Here, enabled by the phase change material Ge3Sb2Te6 (GST-326), we demonstrate a tunable and switchable mid-infrared plasmonic chiral metamaterial in a proof-of-concept experiment. A large tunability range of the circular dichroism response from λ = 4.15 to 4.90 µm is achieved, and we experimentally demonstrate that the combination of a passive bias-type chiral layer with the active chiral metamaterial allows for switchable chirality, that is, the reversal of the circular dichroism sign, in a fully planar, layered design without the need for geometrical reconfiguration. Because phase change materials can be electrically and optically switched, our designs may open up a path for highly integrated mid-IR polarization engineering devices that can be modulated on ultrafast time scales.

Using low-loss phase-change materials for mid-infrared antenna resonance tuning.

We show tuning of the resonance frequency of aluminum nanoantennas via variation of the refractive index n of a layer of phase-change material. Three configurations have been considered, namely, with the antennas on top of, inside, and below the layer. Phase-change materials offer a huge index change upon the structural transition from the amorphous to the crystalline state, both stable at room temperature. Since the imaginary part of their permittivity is negligibly small in the mid-infrared spectral range, resonance damping is avoided. We present resonance shifting to lower as well as to higher wavenumbers with a maximum shift of 19.3% and a tuning figure of merit, defined as the resonance shift divided by the full-width at half-maximum (FWHM) of the resonance peak, of 1.03.

Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.