Background Tapinarof is a novel topical therapeutic aryl hydrocarbon receptor modulating agent in development for the treatment of psoriasis and atopic dermatitis. Objective This multicenter, open-label trial assessed the safety, tolerability, pharmacokinetics (PK), and efficacy of tapinarof cream 1% once daily (QD) under maximal use conditions in extensive plaque psoriasis. Methods Adults with a baseline Physician Global Assessment (PGA) score of ≥ 3 and body surface area (BSA) involvement ≥ 20% received tapinarof cream 1% QD for 29 days. Safety and tolerability assessments included adverse events (AEs) and local tolerability scales. PK parameters were calculated using non-compartmental analysis. Efficacy assessments included change in PGA, Psoriasis Area and Severity Index score, and %BSA affected. Results Twenty-one patients were enrolled. Common AEs were folliculitis, headache, back pain, and pruritus (none led to discontinuation). Tapinarof plasma exposure was low, with the majority of concentrations being below detectable limits. At day 29, 14 patients (73.7%) had a ≥ 1-grade improvement in PGA score and six patients (31.6%) had a ≥ 2-grade improvement; four patients (21.1%) achieved treatment success (PGA 0 or 1 and ≥ 2-grade improvement). Conclusion Tapinarof cream 1% QD was well tolerated, with limited systemic exposure and significant efficacy at 4 weeks in patients with extensive plaque psoriasis. ClinicalTrials.gov Identifier NCT04042103. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00641-4.

This study was designed to characterize and compare the pulmonary effects in distal lung from a low-level exposure to jet propellant-8 fuel (JP-8) and a new synthetic-8 fuel (S-8). It is hypothesized that both fuels have different airway epithelial deposition and responses. Consequently, male C57BL/6 mice were nose-only exposed to S-8 and JP-8 at average concentrations of 53 mg/m3 for 1 hour/day for 7 days. A pulmonary function test performed 24 hr after the final exposure indicated that there was a significant increase in expiratory lung resistance in the S-8 mice, whereas JP-8 mice had significant increases in both inspiratory and expiratory lung resistance compared to control values. Neither significant S-8 nor JP-8 respiratory permeability changes were observed compared to controls, suggesting no loss of epithelial barrier integrity. Morphological examination and morphometric analysis of airway tissue demonstrated that both fuels showed different patterns of targeted epithelial cells: bronchioles in S-8 and alveoli/terminal bronchioles in JP-8. Collectively, our data suggest that both fuels may have partially different deposition patterns, which may possibly contribute to specific different adverse effects in lung ventilatory function.

Pulsed laser deposition (PLD) from a hot pressed manganese doped ZnS target using a KrF laser, has produced a high rate deposition method for growing luminescent thin films. Good stoichiometric quality and typical luminescent crystal structures have been observed with a predominant hexagonal phase and little evidence of the cubic phase. The luminescent characteristics were determined by cathodoluminescence and photoluminescence excitation and stable electroluminescence was observed under pulsed dc conditions with a minimum brightness of 150 cd/m2. PLD film characteristics are compared with those observed in radio-frequency sputtered samples.

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The quality of laser-drilled holes is significantly influenced by the laser peak power, pulse format, and wavelength. Three advanced materials are used to demonstrate the importance of choosing the correct laser parameters for a specific material. The materials are: (1) intermetallic single crystal nickel aluminide (NiAl) alloy; (2) N5, a single crystal nickel-based superalloy; and (3) a silicon carbide (SiC) ceramic matrix composite (CMC). The laser peak power is varied in terms of the pulse duration and format. For low peak powers, long pulse format (pulse lengths on the order of ms), conventional and also shaped-pulse (burst) commercial rod Nd:YAG laser systems were used. For high peak powers, a short pulse format was adopted for the laser used, namely a cw-pumped Q-switched or modelocked/Q-switched Nd:YAG oscillator followed by a cw-pumped multipass amplifier using a face-pumped, total internal reflection Nd:YAG slab as the gain medium. Finally, a KrF excimer laser operating at a 248 nm wavelength was used. The excimer wavelength was chosen to be close to the Nd:YAG fourth harmonic.