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Abstract Tapinarof cream 1% (VTAMA®; Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2 years of age, and for atopic dermatitis in adults and children down to 2 years of age. The PSOARING phase 3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52 weeks (NCT03956355, NCT03983980, NCT04053387). Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points from baseline at week 12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment. Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387.

Our actions arise from our beliefs about life: what we need and how best to achieve it. This article asks English language teachers to undertake an open-minded examination of some long-held beliefs in our profession and of the teaching practices that derive from those beliefs. Perhaps, based on this examination, teachers may wish to modify some beliefs and, correspondingly, change some practices. The particular beliefs examined in the article are as follows: people who begin second language learning at a younger age will be more successful than those who start at an older age; native speaker varieties of English (e.g., those spoken native-English speaking countries) should be valued over non-native varieties (e.g., those spoken in outer and expanding circle countries); the best outcome is for second language learners to use English only and stop using their mother tongue in and out of the classroom; in second language instruction, systematic, explicit and detailed instruction of grammar deserves top priority; vocabulary is considered less important than grammar; pragmatic competence need not be taught as students can acquire it on their own; learning depends on suffering, thus the famous saying “no pain, no gain”; teaching learning strategies deserves a great deal of attention; teaching materials should be difficult in order to move learning forward, and only lazy and uninformed teachers use cooperative learning.

The low electronegativity of Si gives rise to a variety of nonconventional intermolecular interactions in clusters of silanes and their derivatives, which have not been well characterized yet. Herein, we characterize the structures of various isomers of bare and Ar-tagged SiH3OH2+SiH4 dimers composed of protonated silanol and silane by infrared photodissociation (IRPD) of mass-selected ions and dispersion-corrected density functional calculations (B3LYP-D3/aug-cc-pVTZ). The analysis of the IRPD spectra recorded in the OH stretch range reveals the competition between two types of nonconventional hydrogen bonds (H-bonds). The first one represents a OH⋯HSi ionic dihydrogen bond (DHB), in which SiH4 interacts with the H2O moiety of SiH3OH2+. The second one represents a charge-inverted SiH⋯Si ionic H-bond (CIHB), in which the SiH4 ligand interacts with the SiH3 moiety of SiH3OH2+. The latter may also be considered as a weak three-centre two-electron (3c–2e) bond. Although both types of H-bonds are computed to have comparable interaction strengths for SiH3OH2+SiH4 (D0 ≈ 35–40 kJ mol−1), DHB isomers dominate the population in the supersonic plasma expansion, while the abundance of CIHB isomers is roughly one order of magnitude lower, probably as a result of entropic factors. [ABSTRACT FROM AUTHOR]

SinHm+ cations are important constituents in silane plasmas and astrochemical environments. Protonated disilane (Si2H7+) was shown to have a symmetric three-centre two-electron (3c–2e) Si–H–Si bond that can also be considered as a strong ionic charge-inverted hydrogen bond with polarity Siδ+–Hδ−–Siδ+. Herein, we extend our previous work to larger SinH4n−1+ cations, formally resulting from adding SiH4 molecules to a SiH3+ core. Infrared spectra of size-selected SinH4n−1+ ions (n = 2–8) produced in a cold SiH4/H2/He plasma expansion are analysed in the SiH stretch range by complementary dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ) to reveal their bonding characteristics and cluster growth. The ions with n = 2–4 form a linear inorganic H–(Si–H)n hydride wire with adjacent Si–H–Si 3c–2e bridges, whose strength decreases with n, as evident from their characteristic and strongly IR active SiH stretch fundamentals in the range 1850–2100 cm−1. These 3c–2e bonds result from the lowest-energy valence orbitals, and their high stability arises from their delocalization along the whole hydride wire. For SinH4n−1+ with n ≥ 5, the added SiH4 ligands form weak van der Waals bonds to the Si4H19+ chain. Significantly, because the SinH4n−1+ hydride wires are based on penta-coordinated Si atoms leading to supersaturated hydrosilane ions, analogous wires cannot be formed by isovalent carbon. [ABSTRACT FROM AUTHOR]