Nature and dynamics of ice-stream beds: assessing their role in ice-sheet stability

Ice streams are fast flowing outlet glaciers through which over 90% of the ice stored within the Antarctic Ice Sheet drains. The dynamic behaviour of ice streams is therefore crucial in controlling the mass balance of the ice sheet. Over the past few decades, Antarctica has been losing mass. Much of this mass loss has been focussed around coastal regions of the Antarctic Ice Sheet. Some of the most dramatic changes such as grounding-line retreat, acceleration and surface elevation change have been observed in Pine Island Glacier (PIG) and its neighbouring ice streams. This is of particular concern because these ice streams account for 10% of the discharge from the west Antarctic Ice Sheet and therefore have the potential to contribute significantly to global sea-level rise. One of the key challenges in accurately forecasting this future sea-level rise is improving understanding of processes occurring at the beds of ice streams. This requires detailed knowledge of the properties and dynamics of the bed. This thesis aims to address this knowledge gap by investigating the spatial and temporal characteristics of the bed of PIG using high-resolution geophysical data acquired in its trunk and tributaries and beneath the ice shelf. The thesis begins by analysing radar-derived high-resolution maps of subglacial topography. These data show a contrasting topography across the ice-bed interface. These diverse subglacial landscapes have an impact on ice flow through form drag, controlled by the size and orientation of bedrock undulations and protuberances. The next chapter provides a quantitative analysis of these landscapes using Fast Fourier analysis of subglacial roughness. This analysis investigates the roughness signature of subglacial bedforms and the how the orientation and wavelength of roughness elements determine their correlation with ice dynamic parameters. The slow-flowing inter-tributary site is found to have a distinct signature comparable to “ribbed” patterns of modelled basal shear stress and transverse “mega rib” bedforms. Roughness oriented parallel to ice flow with wavelengths approaching mean ice thickness are found to have the highest correlation with ice dynamic parameters. The temporal stability of PIG is analysed using repeat radar measurements. No significant change is observed over a period of 3-6 years with no evidence of rapid erosion or the evolution of subglacial bedforms as observed in previous repeat measurements of ice-stream beds elsewhere in Antarctica. This suggests that the widespread deforming till layer detected in extensive seismic reflection surveys is in steady state. Lastly, the thesis explores geomorphological evidence of twentieth-century grounding-line retreat beneath PIG Ice Shelf using high-resolution geophysical data acquired from autonomous underwater vehicle surveys. Evidence of erosion, deposition, meltwater flow and post-glacial modification is observed in fine detail. The observed distribution of sediment supported previous surveys indicating a geological transition coinciding with the ridge that acted as a former stable grounding-line location. Metre-scale resolution images of recently deglaciated ice stream beds were found to reveal bedforms that are not detectable with traditional offshore bathymetric surveys. Together these findings reveal the role of short wavelength topography as both an influence on, and product of fast ice stream flow. It also highlights the spatial diversity of subglacial environments and the need to focus future research on tying detailed observations of ice-stream beds with knowledge of basal properties over time

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients