Both the Arctic and Antarctic sea ice extents (SIEs) from 44 coupled models in the Coupled Model Intercomparison Project Phase 6 (CMIP6) are evaluated by comparing them with observations and CMIP5 results. The CMIP6 multimodel mean can adequately reproduce the seasonal cycles of both the Arctic and Antarctic SIE. The observed Arctic September SIE declining trend (−0.82 ± 0.18 million km 2 per decade) between 1979 and 2014 is slightly underestimated in CMIP6 models (−0.70 ± 0.06 million km 2 per decade). The observed weak but significant upward trend of the Antarctic SIE is not captured, which was an issue already in the CMIP5 phase. Compared with CMIP5 models, CMIP6 models have lower intermodel spreads in SIE mean values and trends, although their SIE biases are relatively larger. The CMIP6 models did not reproduce the new summer tendencies after 2000, including the faster decline of Arctic SIE and the larger interannual variability in Antarctic SIE.

Using state‐of‐the‐art models from the Coupled Model Intercomparison Project phase 5 (CMIP5), this study found the upper Arctic Ocean likely to freshen considerably in the future. Arctic Ocean average sea surface salinity is projected to decrease by 1.5 ± 1.1 psu, and the liquid freshwater column is projected to increase by 5.4 ± 3.8 m by the end of the 21st century under the Representative Concentration Pathway 8.5 (RCP8.5) scenario. Most freshening would occur in the Arctic Ocean basins, that is, the Canada, Makarov, and Amundsen basins. Anomalies in freshwater flux from sea ice melt, Bering Strait inflow, net precipitation (P‐E), river runoff, and freshwater through the Barents Sea Opening (BSO) would contribute to Arctic Ocean freshening. CMIP5 historical and RCP8.5 experiments showed that the respective projected contributions from BSO freshwater flux, river runoff, P‐E, and Bering Strait inflow are about 6.4, 5.0, 2.7, and 2.2 times the contribution from sea ice melt averaged throughout the 21st century. Contributions from sea ice melt and Bering Strait inflow would increase and then decrease gradually, while those from BSO freshwater flux, river runoff, and P‐E would increase continuously. The CMIP5 models are able to simulate the Arctic Ocean freshwater system more accurately than CMIP3 models. However, the simulated rate of increase of freshwater content (296 ± 232 km3/yr) is weaker than estimated (600 ± 300 km3/yr) based on observations (1992–2012). Moreover, the simulated BSO and Davis Strait freshwater fluxes still exhibit substantial intermodel spread and they differ considerably from observed values.

Objective:To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers and participants with multiple sclerosis (MS).Methods:In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1–100 mg/kg) of BIIB033 or placebo were administered via IV infusion or subcutaneous injection to 72 healthy volunteers, and multiple ascending doses (MAD; 0.3–100 mg/kg; 2 doses separated by 14 days) of BIIB033 or placebo were administered via IV infusion to 47 participants with relapsing-remitting or secondary progressive MS. Safety assessments included adverse event (AE) monitoring, neurologic examinations, conventional and nonconventional MRI, EEG, optical coherence tomography, retinal examinations, and evoked potentials. Serum and CSF PK as well as the immunogenicity of BIIB033 were also evaluated.Results:All 72 healthy volunteers and 47 participants with MS were included in the safety analyses. BIIB033 infusions were well tolerated. The frequency of AEs was similar between BIIB033 and placebo. There were no serious AEs or deaths. No clinically significant changes in any of the safety measures were observed. BIIB033 PK was similar between healthy volunteers and participants with MS. Doses of ≥10 mg/kg resulted in BIIB033 concentrations similar to or higher than the concentration associated with 90% of the maximum remyelination effect in rat remyelination studies. The incidence of anti-drug antibody production was low.Conclusions:The emerging safety, tolerability, and PK of BIIB033 support advancing BIIB033 into phase II clinical development as a potential treatment for CNS demyelination disorders.Classification of evidence:This study provides Class I evidence that BIIB033 is well tolerated and safe (serious adverse event rate 0%, 95% confidence interval 0–7.6%).