Observations of offshore freshened groundwater and saline groundwater discharge along continental shelves have important implications for water resources, ecosystem function, and the composition of the ocean, but they cannot be explained by basic theory. We show that these independent observations are linked and result from processes that drive variable‐density groundwater flow through the spatial heterogeneity that is ubiquitous in geologic formations. We use lithologic data to develop geostatistical models that mimic the architecture of coastal aquifers. Simulation of groundwater flow and salt transport through these random realizations shows that heterogeneity produces spatially complex subsurface salinity distributions that extend tens of kilometers offshore, even at steady state. The associated density gradients drive high saline groundwater circulation rates that cannot be predicted by equivalent homogeneous models. Results suggest that these phenomena may be common along continental shelves, potentially altering estimates of ocean chemical budgets and impacting coastal water management for future generations.

Iptacopan (LNP023) is a novel, oral selective inhibitor of complement factor B under clinical development for paroxysmal nocturnal hemoglobinuria (PNH). In this ongoing open-label phase 2 study, PNH patients with active hemolysis were randomized to receive single-agent iptacopan twice-daily, at a dose of either 25 mg for 4 weeks followed by 100 mg for up to 2 years (cohort 1) or 50 mg for 4 weeks followed by 200 mg for up to 2 years (cohort 2). At the time of interim analysis, of 13 PNH patients enrolled, all 12 evaluable for efficacy achieved the primary endpoint of reduction in serum lactate dehydrogenase (LDH) levels by at least 60% by week 12 as compared to baseline; mean LDH levels dropped rapidly and durably, namely by 77% and 85% at week 2 and by 86% and 86% at week 12 in cohorts 1 and 2, respectively. Most patients achieved a clinically meaningful improvement in hemoglobin levels and all but one patient remained transfusion-free up to week 12. Other markers of hemolysis, including bilirubin, reticulocytes and haptoglobin, showed consistent improvements. No thromboembolic events were reported, and iptacopan was well tolerated, with no severe or serious adverse events reported up until the data cutoff. In addition to the previously reported beneficial effect of iptacopan add-on therapy to eculizumab, this study showed that iptacopan monotherapy in treatment-naïve PNH patients resulted in normalization of hemolytic markers and rapid transfusion-free improvement of hemoglobin levels in most patients. Registered at www.clinicaltrials.gov as NCT03896152.

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During the design of Human-Computer Interaction (HCI) systems, the creation of visual artefacts forms an important part of design. On one hand producing a visual artefact has a number of advantages: it helps designers to externalise their thought and acts as a common language between different stakeholders. On the other hand, if an inappropriate visualisation method is employed it could hinder the design process. To support the design of HCI systems, this paper reviews the categorisation of visualisation methods used in HCI. A keyword search is conducted to identify a) current HCI design methods, b) approaches of selecting these methods. The resulting design methods are filtered to create a list of just visualisation methods. These are then categorised using the approaches identified in (b). As a result 23 HCI visualisation methods are identified and categorised in 5 selection approaches (The Recipient, Primary Purpose, Visual Archetype, Interaction Type, and The Design Process).