Long-term outcomes for Asian patients with X-linked hypophosphataemia : rationale and design of the SUNFLOWER longitudinal, observational cohort study

Introduction X-linked hypophosphataemic rickets/osteomalacia (XLH) is a chronic, debilitating genetic disease characterised by skeletal abnormalities and growth disorder. The burden of XLH begins in childhood and continues throughout life. Conventional medical therapy with phosphate, active vitamin D and surgery do not address the underlying pathophysiology of the disease. While treatment during childhood may improve bone deformity and growth retardation, a large proportion of adult patients still fail to reach normal stature. Furthermore, adult patients with XLH report comorbidities associated with unresolved childhood disease, as well as newly developed disease-related complications and significantly impaired quality of life (QOL). Despite the multiple negative aspects of XLH, Asian consensus statements for diagnosis and management are lacking. Methods and analysis The Study of longitUdinal observatioN For patients with X-Linked hypOphosphataemic rickets/osteomalacia in collaboration With Asian partnERs study is a longitudinal observational cohort study of patients with XLH, designed to determine the medical characteristics and burdens (physical, emotional and financial) of this progressive disease and to evaluate the impact of treatment (including the use of burosumab) on clinical outcomes. The study was initiated in April 2018, and registration will remain open until 30 April 2022. The sample size planned for analyses is 160 patients, consisting of 100 patients in Japan and 60 patients in Korea. Up to 5 years of observation are planned per patient, from enrolment through to April 2023. Prospective and retrospective data will be collected to evaluate variables, including height/growth, rickets severity score, QOL, motor function and biomarkers for phosphate metabolism and bone turnover. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Osaka University, the Ethics Committee of Kyowa Kirin Co and by the Ethics Committee of each participating medical institution. Two interim analyses and associated publications are planned using retrospective and enrolment data at year 1 and results at year 3

Distinct control mechanism of fine-grained sediments from Yellow River and Kyushu supply in the northern Okinawa Trough since the last glacial

© 2017. American Geophysical Union. All Rights Reserved. High-resolution multiproxy records, including clay minerals and Sr-Nd-Pb isotopes of the clay-sized silicate fraction of sediments from IODP Site U1429 in the northern Okinawa Trough, provide reliable evidence for distinct control mechanism on fine-grained sediments input from the Yellow River and the southern Japanese Islands to the northern Okinawa Trough since 34 ka BP. Provenance analysis indicates that the sediments were mainly derived from the Yellow River and the island of Kyushu. Since the last glacial, clay-sized sediments transported from the Yellow River to the study site were strongly influenced by sea-level fluctuation. During low sea-level stage (∼34–14 ka BP), the paleo-Yellow River mouth was positioned closer to the northern Okinawa Trough, favoring large fluvial discharge or even direct input of detrital sediments, which resulted about four times more flux of clay-sized sediments supply to the study area as during the relatively high sea-level stage (∼14–0 ka BP). The input of Kyushu-derived clay-sized sediments to the study site was mainly controlled by the Kuroshio Current and Tsushima Warm Current intensity, with increased input in phase with weakened Kuroshio Current/Tsushima Warm Current. Our study suggests that the Kuroshio Current was very likely flowed into the Okinawa Trough and thus influenced the fine-grained sediment transport in the area throughout the last glacial and deglacial. During ∼34–11 ka BP, the Kyushu clay-sized sediment input was mainly controlled by the Kuroshio Current. Since ∼11 ka BP, the occurrence of Tsushima Warm Current became important in influencing the Kyushu fine-grained sediment input to the northern Okinawa Trough