Going against the flow: Pinning points in the Ross Ice Shelf, Antarctica

The ice shelves surrounding much of the Antarctic continent are supported by pinning points, sites of localised grounding where the floating ice runs aground on the seafloor. Pinning points regulate ice shelf flow and thickness by generating flow resistance, and can in turn, modify grounding line position and tributary glacier dynamics. Ice rises and rumples, the surface topographic expressions of pinning points, are common features in the Ross Ice Shelf (RIS), West Antarctica. Large ice rises in the RIS are known to contribute to flow resistance and ice shelf stability but are unlikely to change over the coming decades, while smaller-scale ice rumples are more vulnerable to changes in the degree of basal contact. This thesis examines how pinning points regulate the present-day flow of the RIS. Two separate studies are undertaken to elucidate the full range of ice mechanical and dynamical effects associated with smaller-scale pinning points that are often overlooked in numerical models of the ice sheet-ice shelf system. The first study presents a mechanical inventory of 15 pinning points in the RIS. A force budget technique is applied to quantify the magnitude and direction of resistive forces generated by individual pinning points. Basal drag inferred from the pinning point force budgets varies by two orders of magnitude, implying that variations in the subglacial material directly affect the flow resistance generated by each feature. Of all the RIS pinning points, a collection of smaller-scale, lightly-grounded ice rumples are remarkable for generating flow resistance comparable to large ice rises. These ice rumples are investigated in more detail in the second study. The second study uses a numerical model of RIS and tributary ice stream flow to examine how the Shirase Coast Ice Rumples (SCIR) in the eastern RIS regulate the behaviour of the interconnected ice shelf-ice stream system. Two configurations are compared: (1) the present-day RIS with the SCIR included and (2) a perturbed model with the SCIR removed from the model domain. Differences between the two simulations demonstrate how the SCIR modify ice flow, thickness, grounding line position, mass flux, and the distribution of stresses resisting ice flow. The SCIR promote a slower-flowing eastern RIS, a more seaward grounding line position, and a decrease in mass flux through the MacAyeal and Bindschadler Ice Stream outlets of 2.3% and 3.4%, respectively, in comparison to an RIS configuration without the SCIR. When the SCIR are removed, the flow resistance generated by other grounded features increases to maintain the balance of forces acting on ice shelf flow. This mechanism limits the magnitude of the RIS speed-up. The mechanical and dynamical effects of pinning points are timely mechanisms to investigate given current observations of rapid mass loss along west Antarctic coastal margins triggered by ocean warming. This thesis quantifies both the immediate and multi-decadal consequences of changes in pinning point configuration and elucidates why it is important to include even small-scale pinning points in model inversions for ice material properties, as well as in model projections of variability in the ice sheet-ice shelf system

Tidal Modulation of a Lateral Shear Margin: Priestley Glacier, Antarctica

We use high resolution, ground-based observations of ice displacement to investigate ice deformation across the floating left-lateral shear margin of Priestley Glacier, Terra Nova Bay, Antarctica. Bare ice conditions allow us to fix survey marks directly to the glacier surface. A combination of continuous positioning of a local reference mark, and repeat positioning of a network of 33 stakes installed across a 2 km width of the shear margin are used to quantify shear strain rates and the ice response to tidal forcing over an 18-day period. Along-flow velocity observed at a continuous Global Navigation Satellite Systems (GNSS) station within the network varies by up to ∼30% of the mean speed (±28 m a−1) over diurnal tidal cycles, with faster flow during the falling tide and slower flow during the rising tide. Long-term deformation in the margin approximates simple shear with a small component of flow-parallel shortening. At shorter timescales, precise optical techniques allow high-resolution observations of across-flow bending in response to the ocean tide, including across-flow strains on the order of 10–5. An elastodynamic model informed by the field observations is used to simulate the across-flow motion and deformation. Flexure is concentrated in the shear margin, such that a non-homogeneous elastic modulus is implied to best account for the combined observations. The combined pattern of ice displacement and ice strain also depends on the extent of coupling between the ice and valley sidewall. These conclusions suggest that investigations of elastic properties made using vertical ice motion, but neglecting horizontal displacement and surface strain, will lead to incorrect conclusions about the elastic properties of ice and potentially over-simplified assumptions about the sidewall boundary condition

Ultrasonic and seismic constraints on crystallographic preferred orientations of the Priestley Glacier shear margin, Antarctica

Crystallographic preferred orientations (CPOs) are particularly important in controlling the mechanical properties of glacial shear margins. Logistical and safety considerations often make direct sampling of shear margins difficult, and geophysical measurements are commonly used to constrain the CPOs. We present here the first direct comparison of seismic and ultrasonic data with measured CPOs in a polar shear margin. The measured CPO from ice samples from a 58 m deep borehole in the left lateral shear margin of the Priestley Glacier, Antarctica, is dominated by horizontal c axes aligned sub-perpendicularly to flow. A vertical-seismic-profile experiment with hammer shots up to 50 m away from the borehole, in four different azimuthal directions, shows velocity anisotropy of both P waves and S waves. Matching P-wave data to the anisotropy corresponding to CPO models defined by horizontally aligned c axes gives two possible solutions for the c-axis azimuth, one of which matches the c-axis measurements. If both P-wave and S-wave data are used, there is one best fit for the azimuth and intensity of c-axis alignment that matches the measurements well. Azimuthal P-wave and S-wave ultrasonic data recorded in the laboratory on the ice core show clear anisotropy of P-wave and S-wave velocities in the horizontal plane that match that predicted from the CPO of the samples. With quality data, azimuthal increments of 30∘ or less will constrain well the orientation and intensity of c-axis alignment. Our experiments provide a good framework for planning seismic surveys aimed at constraining the anisotropy of shear margins

Microstructure and crystallographic preferred orientations of an azimuthally oriented ice core from a lateral shear margin: Priestley Glacier, Antarctica

A 58 m long azimuthally oriented ice core has been collected from the floating lateral sinistral shear margin of the lower Priestley Glacier, Terra Nova Bay, Antarctica. The crystallographic preferred orientations (CPO) and microstructures are described in order to correlate the geometry of anisotropy with constrained large-scale kinematics. Cryogenic Electron Backscatter Diffraction analysis shows a very strong fabric (c-axis primary eigenvalue ∼0.9) with c-axes aligned horizontally sub-perpendicular to flow, rotating nearly 40° clockwise (looking down) to the pole to shear throughout the core. The c-axis maximum is sub-perpendicular to vertical layers, with the pole to layering always clockwise of the c-axes. Priestley ice microstructures are defined by largely sub-polygonal grains and constant mean grain sizes with depth. Grain long axis shape preferred orientations (SPO) are almost always 1–20° clockwise of the c-axis maximum. A minor proportion of “oddly” oriented grains that are distinct from the main c-axis maximum, are present in some samples. These have horizontal c-axes rotated clockwise from the primary c-axis maximum and may define a weaker secondary maximum up to 30° clockwise of the primary maximum. Intragranular misorientations are measured along the core, and although the statistics are weak, this could suggest recrystallization by subgrain rotation to occur. These microstructures suggest subgrain rotation (SGR) and recrystallization by grain boundary migration recrystallization (GBM) are active in the Priestley Glacier shear margin. Vorticity analysis based on intragranular distortion indicates a vertical axis of rotation in the shear margin. The variability in c-axis maximum orientation with depth indicates the structural heterogeneity of the Priestley Glacier shear margin occurs at the meter to tens of meters scale. We suggest that CPO rotations could relate to rigid rotation of blocks of ice within the glacial shear margin. Rotation either post-dates CPO and SPO development or is occurring faster than CPO evolution can respond to a change in kinematics

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Going against the flow: Pinning points in the Ross Ice Shelf, Antarctica

The ice shelves surrounding much of the Antarctic continent are supported by pinning points, sites of localised grounding where the floating ice runs aground on the seafloor. Pinning points regulate ice shelf flow and thickness by generating flow resistance, and can in turn, modify grounding line position and tributary glacier dynamics. Ice rises and rumples, the surface topographic expressions of pinning points, are common features in the Ross Ice Shelf (RIS), West Antarctica. Large ice rises in the RIS are known to contribute to flow resistance and ice shelf stability but are unlikely to change over the coming decades, while smaller-scale ice rumples are more vulnerable to changes in the degree of basal contact. This thesis examines how pinning points regulate the present-day flow of the RIS. Two separate studies are undertaken to elucidate the full range of ice mechanical and dynamical effects associated with smaller-scale pinning points that are often overlooked in numerical models of the ice sheet-ice shelf system. The first study presents a mechanical inventory of 15 pinning points in the RIS. A force budget technique is applied to quantify the magnitude and direction of resistive forces generated by individual pinning points. Basal drag inferred from the pinning point force budgets varies by two orders of magnitude, implying that variations in the subglacial material directly affect the flow resistance generated by each feature. Of all the RIS pinning points, a collection of smaller-scale, lightly-grounded ice rumples are remarkable for generating flow resistance comparable to large ice rises. These ice rumples are investigated in more detail in the second study. The second study uses a numerical model of RIS and tributary ice stream flow to examine how the Shirase Coast Ice Rumples (SCIR) in the eastern RIS regulate the behaviour of the interconnected ice shelf-ice stream system. Two configurations are compared: (1) the present-day RIS with the SCIR included and (2) a perturbed model with the SCIR removed from the model domain. Differences between the two simulations demonstrate how the SCIR modify ice flow, thickness, grounding line position, mass flux, and the distribution of stresses resisting ice flow. The SCIR promote a slower-flowing eastern RIS, a more seaward grounding line position, and a decrease in mass flux through the MacAyeal and Bindschadler Ice Stream outlets of 2.3% and 3.4%, respectively, in comparison to an RIS configuration without the SCIR. When the SCIR are removed, the flow resistance generated by other grounded features increases to maintain the balance of forces acting on ice shelf flow. This mechanism limits the magnitude of the RIS speed-up. The mechanical and dynamical effects of pinning points are timely mechanisms to investigate given current observations of rapid mass loss along west Antarctic coastal margins triggered by ocean warming. This thesis quantifies both the immediate and multi-decadal consequences of changes in pinning point configuration and elucidates why it is important to include even small-scale pinning points in model inversions for ice material properties, as well as in model projections of variability in the ice sheet-ice shelf system

Improving access to melarsomine therapy: treating canine heartworm infection in a high-volume, outpatient community clinic setting

Abstract Background Models that provide high-quality veterinary care for more affordable prices are emerging, but not well documented outside of wellness and preventative care. Effective treatment guidelines for heartworm disease have been developed by the American Heartworm Society; however, not all owners are able to access treatment due to the high costs associated with sick and emergency care services. Methods To increase access to high-quality adulticidal treatment of canine heartworm disease, we developed and implemented a technician-leveraged heartworm treatment protocol for high-volume, outpatient community clinic settings based on the American Heartworm Society guidelines. Modifications were few and included limited pre-treatment blood work, pre-injection sedation, post-injection pain medication, and a reduced exercise restriction period. We monitored retention rates for 556 dogs throughout treatment, evaluated treatment success (defined as no antigen detection 9 months post treatment) for patients that returned for post-treatment antigen testing, and reported on adverse reactions and therapy adherence throughout treatment. Results Of the patients that began adulticide therapy, 539/556 (97%) successfully completed the three-injection series. No microfilariae were detected in 99% (428/433) of those who returned for post-injection microfilaria testing. Among those that returned for or reported the results of post-injection antigen testing, no antigen was detected for 99% (245/248) and no microfilariae were detected for 99.5% (200/201). During the course of treatment, 483/539 (90%) of patients experienced at least one adverse reaction, with the most frequently reported types being behavioral and injection site reactions. 25/539 (4.6%) of owners sought additional medical care for adverse reactions at some point during the treatment course. The overall mortality rate was 1.3% (7/556). Conclusions This study represents the first evaluation of a heartworm treatment protocol optimized for implementation in a high-volume, outpatient community clinic setting. Our findings align with those previously reported in private practice or tertiary referral centers, illustrating that through the inclusion of pre-treatment blood work, employing short-acting or reversible sedatives, ensuring proper analgesia, minimizing the use of ancillary diagnostics, reducing the duration of in-clinic monitoring while focusing on outpatient care, and maximizing technician involvement, we can deliver effective and safe melarsomine therapy at a more affordable cost to pet owners. Graphical Abstrac

The epidemiology of hospital inpatient exposure to SARS-CoV-2: A retrospective cohort study

Background COVID-19 has posed a significant challenge to Infection and Prevention Control practices in UK hospitals. The epidemiology of nosocomial COVID-19 is not yet fully understood. Methods In this cohort study, all incidences of patient-to-patient exposure on non-COVID wards between October and December 2020 at a UK hospital trust were identified. Patient contacts were traced, and data collected on SARS-CoV-2 testing, length of stay and mortality outcome. Factors associated with acquiring infection, mortality and length of stay were investigated using multivariable regression and Cox proportional hazard modelling respectively. Findings 575 patients were exposed across 24 clusters. 118 (19.5%) tested positive for SARS-CoV-2 within 14 days of exposure. Evidence of multiple introductions were found in four clusters and this was associated with a greater secondary attack rate (SAR). There was no detected transmission in 6 of the clusters. Sharing a bay and spending a longer time on the ward with the index case were associated with acquiring infection (ORs of 3.8, 95% CI: 1.89, 7.74, and 1.08, 95% CI: 1.01, 1.15 respectively). Half of all secondary cases did not develop symptoms. Patients acquiring symptomatic COVID-19 had four-fold increased odds of mortality. There was no difference in mortality between asymptomatic COVID-positive and COVID-negative patients. Interpretation Exposure to COVID-19 in hospital often, but not always, leads to transmission. This study highlights the large mortality risk associated with symptomatic nosocomial COVID-19 infection and is the first to describe factors that can be used to understand a contact’s risk of developing infection post-exposure. Funding Non