To provide an observational basis for the Intergovernmental Panel on Climate Change projections of a slowing Atlantic meridional overturning circulation (MOC) in the 21st century, the Overturning in the Subpolar North Atlantic Program (OSNAP) observing system was launched in the summer of 2014. The first 21-month record reveals a highly variable overturning circulation responsible for the majority of the heat and freshwater transport across the OSNAP line. In a departure from the prevailing view that changes in deep water formation in the Labrador Sea dominate MOC variability, these results suggest that the conversion of warm, salty, shallow Atlantic waters into colder, fresher, deep waters that move southward in the Irminger and Iceland basins is largely responsible for overturning and its variability in the subpolar basin.

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis.

The Atlantic Meridional Overturning Circulation (AMOC) is a key component of the global climate system through its transport of heat and freshwater. The subpolar North Atlantic (SPNA) is a region where the AMOC is actively developed and shaped though mixing and water mass transformation and where large amounts of heat are released to the atmosphere. Two hydrographic transbasin sections in the summers of 2014 and 2016 provide highly spatially resolved views of the SPNA velocity and property fields on a line from Canada to Greenland to Scotland. Estimates of the AMOC, isopycnal (gyre-scale) transport, and heat and freshwater transport are derived from the observations. The overturning circulation, the maximum in northward transport integrated from the surface to seafloor and computed in density space, has a high range, with 20.6 ± 4.7 Sv in June-July 2014 and 10.6 ± 4.3 Sv in May-August 2016. In contrast, the isopycnal (gyre-scale) circulation was lowest in summer 2014: 41.3 ± 8.2 Sv compared to 58.6 ± 7.4 Sv in 2016. The heat transport (0.39 ± 0.08 PW in summer 2014, positive is northward) was highest for the section with the highest AMOC, and the freshwater transport was largest in summer 2016 when the isopycnal circulation was high (À0.25 ± 0.08 Sv). Up to 65% of the heat and freshwater transport was carried by the isopycnal circulation, with isopycnal property transport highest in the western Labrador Sea and the eastern basins (Iceland Basin to Scotland).

Reflectance confocal microscopy (RCM) allows the identification of four malignant melanoma (MM) subtypes: dendritic-cell (DC), round cell (RN), dermal-nest (DN) and combinedtype (CT). The aim was to study the biomolecular profile of MM RCM-subtypes. 85 MM were evaluated by RCM and characterized by clinical, dermoscopic and histopatological analyses. DC and RC melanoma were generally Radial Growth Phase in stage I and II, while CT and DN were Vertical Growth Phase in stage III and IV. Ki67, as shown by immunohistochemistry, was significantly more expressed in the epidermis of DC and RC. CD271 expression increased from DC to RC and decreased from RC to CT. This correlates with our previously published concept that CD271 has a switch on-off function in melanoma progression. ABCB5 expression was lower in RC than in DC, CT and DN. Co-expression of BMF and BRAFv660E was observed in CT, while it inversely correlated in DC, RC and DN. Nestin and Sox2 were highly co-expressed in CT and DN, indicating a more aggressive behaviour of CT and DN, as compared to DC. RNAs extracted from paraffin-embedded melanoma tissues were analysed for the expression of 770 genes by NanoString technology. The analysis revealed significant differences in the expression of genes involved in chemotaxis, inflammation, cell-cell adhesion, cell motility and angiogenesis. While CT melanomas were able to generate spheroids, DC did not form a compact spheroid, probably because of its less proliferative capacity, as shown by MTT assay. Collagen invasion assay confirmed that DC is a less aggressive tumour, as compared to the other RCM-subtypes. These results represent a first step to develop a new method to diagnose and manage melanoma, reaching a more accurate patient/tumour tailored therapeutic approach.