0000000000270523
AUTHOR
P. Chan
Freshening of the Alaska Coastal Current recorded by coralline algal Ba/Ca ratios
Arctic Ocean freshening can exert a controlling influence on global climate, triggering strong feedbacks on ocean‐atmospheric processes and affecting the global cycling of the world’s oceans. Glacier‐fed ocean currents such as the Alaska Coastal Current are important sources of freshwater for the Bering Sea shelf, and may also influence the Arctic Ocean freshwater budget. Instrumental data indicate a multiyear freshening episode of the Alaska Coastal Current in the early 21st century. It is uncertain whether this freshening is part of natural multidecadal climate variability or a unique feature of anthropogenically induced warming. In order to answer this, a better understanding of past var…
TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)
ABSTRACT Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G…
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…