Are focus and givenness prosodically marked in Kinyarwanda and Rwandan English?

This paper concentrates on whether systematic variations in pitch, intensity, and duration can be observed as a function of the focused or discourse-given status of a constituent in Kinyarwanda (Guthrie code JD.61), and a relatively recent variety of “New English” in contact with this Bantu language. Kinyarwanda is a tone language, in which the information-structural notion of focus has been reported to be expressed through changes in word order, with focus appearing clause-finally (Kimenyi 1988, Ndayiragije 1999, Ngoboka 2016). In contrast, Standard English is well-known for the prosodic boost associated with narrowly focused words and the prosodic reduction of post-focal items. Crosslinguistically, the prosodic expression of focus and givenness is progressively being considered a marked feature. Zerbian (2015a) predicts that it should not be found in a second language or a contact variety if it is not already present in the first language of a speaker or a group of speakers. Our study finds no evidence that information focus, exhaustive focus, or givenness systematically affect the prosody of Kinyarwanda. We also find no systematic effect of information structure in the variety of English spoken by our Rwandan participants, confirming that this is probably an area of English that is difficult to acquire

Pathogenic and targetable genetic alterations in 70 urachal adenocarcinomas

Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins (MMR)) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR-deficiency (MMR-d)/MSI-high (MSI-h), whereas 10 of 63 cases (16%) expressed PD-L1. Therefore, anti-PD-1/PD-L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti-EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer. This article is protected by copyright. All rights reserved