Full-Spectrum Flexible Color Printing at the Diffraction Limit

Color printing at the diffraction limit has been recently explored by fabricating nanoscale plasmonic structures with electron beam lithography. However, only a limited color range and constant intensity throughout the structure have been demonstrated. Here we show an alternative, facile approach relying on the direct, open-atmosphere electrohydrodynamic rapid nanodrip printing of controlled amounts of red, green and blue (RGB) quantum dots at a resolution of 250 nm. The narrow emission spectrum of the dots allows the coverage of a very broad color space, exceeding standard RGB (sRGB) of modern display devices. We print color gradients of variable intensity, which to date could not be achieved with diffraction-limited resolution. Showcasing the capabilities of the technology, we present a photo-realistic printed image of a colorful parrot with a pixel size of 250 nm

Direct printing of nanostructures by electrostatic autofocussing of ink nanodroplets

Nanotechnology, with its broad impact on societally relevant applications, relies heavily on the availability of accessible nanofabrication methods. Even though a host of such techniques exists, the flexible, inexpensive, on-demand and scalable fabrication of functional nanostructures remains largely elusive. Here we present a method involving nanoscale electrohydrodynamic ink-jet printing that may significantly contribute in this direction. A combination of nanoscopic placement precision, soft-landing fluid dynamics, rapid solvent vapourization, and subsequent self-assembly of the ink colloidal content leads to the formation of scaffolds with base diameters equal to that of a single ejected nanodroplet. The virtually material-independent growth of nanostructures into the third dimension is then governed by an autofocussing phenomenon caused by local electrostatic field enhancement, resulting in large aspect ratio. We demonstrate the capabilities of our electrohydrodynamic printing technique with several examples, including the fabrication of plasmonic nanoantennas with features sizes down to 50 nm

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B‐rapidly accelerated fibrosarcoma‐mutated advanced melanoma

Background B‐rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF‐mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib). Objective The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib. Methods Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature. Results The most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n = 24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug‐induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n = 25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n = 49) were palmoplantar hyperkeratosis (10%). Conclusion Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events

Transient MEK inhibitor-associated retinopathy in metastatic melanoma

BACKGROUND: Melanoma is one of the most aggressive skin cancers. Recently, selective MEK inhibitors have shown efficacy in patients with advanced BRAF- and NRAS-mutant melanoma. Soon after the initiation of clinical oncology trials with MEK inhibitors, it was observed that some participants developed an eye condition resembling central serous chorioretinopathy. The present article addresses the clinical features and management of these MEK inhibitor-associated retinal syndromes. PATIENTS AND METHODS: Thirty-two patients with advanced cutaneous melanoma were treated with the selective MEK inhibitor binimetinib (MEK162) in three different Phase 1b or 2 clinical trials. Twenty patients on binimetinib monotherapy and 12 on binimetinib plus RAF inhibitor [pan-kinase RAF inhibitor RAF265 (n = 7) or selective BRAF inhibitor encorafenib (LGX818) (n = 5)] combination therapy underwent ophthalmological examinations at regular intervals, including determination of best corrected visual acuity, perimetry, colour vision testing, dilated fundus examination, and multimodal imaging. RESULTS: Grade 1-2 bilateral retinopathies with multiple lesions were observed in 13 of 20 patients on binimetinib monotherapy, 4 of 7 patients on binimetinib plus RAF265 combination therapy, and 2 of 5 patients on binimetinib plus encorafenib combination therapy. In this study population, the rate ranged from 40% to 65%. Retinopathy events appeared during the first 4 weeks, and in some cases, during the first few days of treatment. Patients reported mild and only short-lived visual symptoms. Optical coherence tomography revealed neuroretinal elevations. Central retinal thickness and volume showed dose-dependent increases after the start of treatment, followed by a marked decrease despite continued treatment, which was associated with symptom resolution. No vascular abnormalities were found with fluorescein and indocyanine green angiography. CONCLUSIONS: Treatment with the selective MEK inhibitor binimetinib as a single agent or in combination with RAF inhibitors induced transient retinopathy with multiple bilateral lesions in some patients. Binimetinib-induced retinopathy was usually mild, self-limiting, and tolerable as visual function was not seriously impaired

A natural experiment study: Low-profile double plating versus single plating techniques in midshaft clavicle fractures-Study protocol.

BackgroundSingle plate osteosynthesis is commonly employed when performing surgical stabilization of midshaft clavicle fractures. In recent years, a smaller structural low-profile double plating technique has been described as a possible solution for the high removal rates associated with single plating. A previous meta-analysis has demonstrated that low-profile double plating attains the same healing rates as single plating without a higher chance of fracture-related infections. This meta-analysis, however, was based on relatively small studies. Therefore, a multicentre prospective natural experiment was designed using natural variation in treatment regimens and geographical location of the trauma as treatment allocation mechanism to compare both treatments on a larger scale. This manuscript describes its protocol.Material & methodsPatients (≥16 years) with primary midshaft clavicle fractures that are eligible for operative treatment will be included. Treatment allocation will be determined by the geographical location of the accident and local hospital providing treatment. In two centres, single plating is the treatment of choice for these patients. In two others, low-profile double plating has become the standard treatment. For the low-profile double plating group, one superiorly positioned VariAx 2.0mm and one anterior VariAx 2.4mm or 2.7mm plate will be used. For the single plating group, the standard locally available implant will be used. A total of 336 patients will be included. The primary outcome of interest is re-intervention. Secondary outcomes include complications, operative time, length of incision, functional scores (DASH, EQ-5D-DL, VAS-Pain/Satisfaction) and cost-effectiveness.DiscussionThis study will determine whether low-profile double plating has significant clinical and cost-effective benefits over single plating techniques in midshaft clavicle fractures. The study will also give insight in the performance of a natural experiment study design for orthopedic trauma research.Trial registrationThis study has been registered on ClincialTrials.gov, identifier NCT05579873