Mutations in human SLC26A4 are a common cause of hearing loss associated with enlarged vestibular aqueducts (EVA). SLC26A4 encodes pendrin, an anion-base exchanger expressed in inner ear epithelial cells that secretes HCO 3 -into endolymph. Studies of Slc26a4-null mice indicate that pendrin is essential for inner ear development, but have not revealed whether pendrin is specifically necessary for homeostasis. Slc26a4-null mice are profoundly deaf, with severe inner ear malformations and degenerative changes that do not model the less severe human phenotype. Here, we describe studies in which we generated a binary transgenic mouse line in which Slc26a4 expression could be induced with doxycycline. The transgenes were crossed onto the Slc26a4-null background so that all functional pendrin was derived from the transgenes. Varying the temporal expression of Slc26a4 revealed that E16.5 to P2 was the critical interval in which pendrin was required for acquisition of normal hearing. Lack of pendrin during this period led to endolymphatic acidification, loss of the endocochlear potential, and failure to acquire normal hearing. Doxycycline initiation at E18.5 or discontinuation at E17.5 resulted in partial hearing loss approximating the human EVA auditory phenotype. These data collectively provide mechanistic insight into hearing loss caused by SLC26A4 mutations and establish a model for further studies of EVA-associated hearing loss.

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Background and purpose: This study aimed to evaluate the efficacy of radical radiotherapy and assess prognostic factors in metachronous oligometastatic esophageal cancer (MOEC) patients after initial treatment with curative-intent surgery and/or chemoradiotherapy. Materials and methods: MOEC Patients during 2009-2018 in ÂÂÂ Central Hospital were retrospectively analyzed. Each patient had 5 oligometastatic lesions, and the primary lesions were controlled in this study. Patients were devided into radiotherapy (RT) and non-radiotherapy (NRT) groups. The study endpoints were overall survival (OS) and treatment toxicities. Results: This study included 82 patients who underwent intensity-modulated radiotherapy for MOEC. Median OS were 14 (95% confidence interval [CI], 11.0-17.0) and 7 (95% CI, 4.5-9.5) months for the RT and NRT groups, respectively (P = 0.016). Median OS were 18 (95% CI, 13.6-22.4) and 10 (95% CI, 5.1-14.9) months for lung and bone metastases, respectively (P = 0.010). Median OS were 15 (95% CI, 12.4-17.6) and 10 (95% CI, 7.6-12.4) months for interval time from initial diagnosis to metastasis !12 and <12 months, respectively (P = 0.026). Median OS were 16 (95% CI, 12.2-19.8) and 10 (95% CI, 5.0-15.0) months for biological effective dose (BED 10) ! 60 Gy and BED 10 < 60 Gy, respectively (P = 0.033). Cox multivariate regression analysis showed that treatment modality (RT vs. NRT) was an independent prognostic factor for MOEC patients (hazard ratio: 1.8, 95% CI: 1.1-3.0; P = 0.022). No toxic side effects greater than grade 3 were observed in all patients. Conclusions: Radiotherapy is a feasible and positive treatment for MOEC patients after initial treatment, a radical radiation dose with BED 10 ! 60 Gy has benefits in extending survival. Radical radiotherapy should thus be considered for MOEC patients.

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In this paper, a novel microstrip phased array with dual-polarized and wide-angle scanning in the 2-dimensional (2D) space is proposed. The antenna element consists of a mushroom-shaped patch and two circular patches. Each circular patch is connected with one feeding port. The mushroomshaped patch is excited via capacitive coupling through the gaps between the mushroom-shaped patch and the circular patch. The zeroth-order resonance (ZOR) and TM010 mode resonance are simultaneously generated in the mushroom-shaped patch. The 3dB beamwidth of the antenna element in the 2D space is in the range between 110° and 125°. One 6×6 phased array based on the antenna element is designed, fabricated and measured. The phased array shows dual-polarized wide-angle beam scanning in a range of ±66° in both x-z and y-z planes.