UAV-based investigations into the hydrology and dynamics of the Greenland Ice Sheet

Variation in the rate of meltwater input into the subglacial system of the Greenland Ice Sheet can force dynamic responses on a range of scales from hourly to interannual. Observations of the ice sheet dynamic response are commonly made either through ground-based Global Navigation Satellite System (GNSS) measurements, which can provide continuous and accurate point measurements, or through satellite remote sensing, which can provide regional-scale observations but at coarse temporal resolutions. This thesis investigates the potential of Uncrewed Aerial Vehicles (UAVs) to provide intermediate-level observations of the interactions between ice sheet hydrology and dynamics at a fast-flowing, marine terminating glacier in West Greenland. I first describe the development of a low- cost UAV suitable for deriving ice sheet velocity fields from Structure-from-Motion photogrammetry. In order to geolocate products without using ground control, image locations are determined directly using an on-board L1 GNSS receiver. I validate this method, showing that accuracies are sufficient for producing velocity fields in the ice sheet interior. Next, this method is used, alongside in-situ geophysical observations, to characterise the causes and dynamic influence of a rapid supraglacial lake drainage. I show that rapid drainage can induce a significant dynamic response up to 4 km away from the lake itself, and that fracture history can exert controls on interannual lake drainage behaviour. Finally, I upscale UAV ob- servations using satellite datasets over a ~3,000 km² area, exploring dynamic controls on crevasse hydrology. I find that in compressive mean stress compressive regimes, crevasses are more likely to display ponding and rapid hydrofracture than in extensional regimes, where continuous slow drainage is typical. Continued high-resolution observations are necessary to further identify key controls on the hydrological influences of Greenland Ice Sheet dynamics.Funded by a Natural Environment Research Council studentship awarded through the Cambridge Earth System Science Doctoral Training Partnership (Grant NE/L002507/1). Research logistics funded by the European Research Council as part of the RESPONDER project under the European Union’s Horizon 2020 research and innovation program (Grant 683043)

Glacier surging in the West Kunlun Shan

The cryosphere of High Mountain Asia represents the third-largest glacial system on Earth, with a glacierised area of ~40 800 km2 (Bolch et al., 2012) and a mass balance of -26 ± 12 Gt a-1: ~10% of the global contribution of the cryosphere to sea level rise (Vaughan et al., 2013). The glaciers of the Karakoram and West Kunlun Shan represent the second major global centre of surge activity (Sevestre and Benn, 2015) and also mark a region of anomalous glacier behaviour known as the ’Karakoram Anomaly’ (Hewitt, 2005), whereby widespread glacier stability and even growth contrasts with the global norm (Bhambri et al., 2013; Gardelle et al., 2012; Kääb et al., 2015). Despite the motivations presented by this unusual behaviour, understanding of glacial dynamics in the region is underdeveloped due to a scarcity of data and studies in the area, with even the dominant surge mechanism remaining unclear (Quincey et al., 2015). This study aims to expand the current dataset of surging in the region by characterising a series of surges identified in a small range at the western end of the West Kunlun Shan. This site exists between the Karakoram and the site of the one previous surging study in the region (Yasuda and Furuya, 2015), allowing for the analysis of surging behaviour across a wide longitudinal range. The objectives of this study are: (i) to identify the long-term spatial and temporal distribution of surges in the study region; (ii) to assess surge dynamics over the course of the most recent surges; and (iii) to characterise observed surge behaviour in the context of established surge mechanisms and regional climatic and glaciological behaviour. A combination of a decadal-scale range of remotely sensed imagery, manual tracking of terminus position change, and cross-correlation feature-tracking methods are used to identify and characterise surge dynamics in the range. A total of ten glaciers were observed to surge between 1972–2016 – 11.3% of the total population. Statistical analysis showed that these glaciers were more likely to be wider than non-surging glaciers, which is in line with previous findings, and terminate at lower altitudes, which is a new finding that here is linked to the increased likelihood of warm beds at lower altitudes. Distribution is biased to the northern range in the study area, which could be related to differing topographies in the north and south ranges, but could also be linked to geological differences. Surge dynamics do not conform to classical understandings of surge mechanisms. Some characteristics are indicative of thermal (Svalbard-type) surges, with relatively slow velocities and build-up and termination periods lasting months–years. However, some unusual behaviours are also reminiscent of hydrological surges, including shorter return periods (~4 decades) and surge periods (~2–6 years) than typical thermal surges. These factors have been previously identified in adjacent studies (Quincey et al., 2015; Yasuda and Furuya, 2015), suggesting that the unusual behaviours observed across various surge studies in HMA are not anomalous, but instead indicative of a unique surge mechanism that is related to, but distinct from, traditional surge mechanisms. Finally, observations were made of eight glacier surges that are temporally coincident to an unusual degree, which conflicts with understandings of glacier surging as a behaviour forced entirely by internally regulated mechanisms. Although conclusions presented here are highly speculative, links were made to a hydro-thermodynamic mechanism recently put forward by Dunse et al. (2015) to explain hydrologically forced thermal surging on an outlet glacier of the Austfonna ice cap. This conclusion is supported by records of anomalously high temperatures during the surge initiation period, and can also be interpreted in the context of long-term climate changes in the region, recently linked to increased surge incidence in the Karakoram. This study has expanded the record of surges in the WKS, and made an unusual discovery that further validates recent literature proposing a relationship between surging and climate. These findings are important both in terms of understanding more about regional glaciology and climate, but also in better understanding surge behaviour as a whole

Borehole-Based Characterization of Deep Mixed-Mode Crevasses at a Greenlandic Outlet Glacier

Funder: Aberystwyth University Capital Equipment FundAbstract: Optical televiewer borehole logging within a crevassed region of fast‐moving Store Glacier, Greenland, revealed the presence of 35 high‐angle planes that cut across the background primary stratification. These planes were composed of a bubble‐free layer of refrozen ice, most of which hosted thin laminae of bubble‐rich “last frozen” ice, consistent with the planes being the traces of former open crevasses. Several such last‐frozen laminae were observed in four traces, suggesting multiple episodes of crevasse reactivation. The frequency of crevasse traces generally decreased with depth, with the deepest detectable trace being 265 m below the surface. This is consistent with the extent of the warmer‐than‐modeled englacial ice layer in the area, which extends from the surface to a depth of ∼400 m. Crevasse trace orientation was strongly clustered around a dip of 63° and a strike that was offset by 71° from orthogonal to the local direction of principal extending strain. The traces’ antecedent crevasses were therefore interpreted to have originated upglacier, probably ∼8 km distant involving mixed‐mode (I and III) formation. We conclude that deep crevassing is pervasive across Store Glacier, and therefore also at all dynamically similar outlet glaciers. Once healed, their traces represent planes of weakness subject to reactivation during subsequent advection through the glacier. Given their depth, it is highly likely that such traces—particularly those formed downglacier—survive surface ablation to reach the glacier terminus, where they may represent foci for fracture and iceberg calving

Thermodynamics of a fast-moving Greenlandic outlet glacier revealed by fiber-optic distributed temperature sensing

Funding: This research was funded by the European Research Council as part of the RESPONDER project under the European Union’s Horizon 2020 research and innovation program (grant 683043). R.L. and T.R.C. were supported by Natural Environment Research Council Doctoral Training Partnership studentships (grant NE/ L002507/1). B.H. was supported by a HEFCW/Aberystwyth University Capital Equipment Grant.Measurements of ice temperature provide crucial constraints on ice viscosity and the thermodynamic processes occurring within a glacier. However, such measurements are presently limited by a small number of relatively coarse-spatial-resolution borehole records, especially for ice sheets. Here, we advance our understanding of glacier thermodynamics with an exceptionally high-vertical-resolution (~0.65 m), distributed-fiber-optic temperature-sensing profile from a 1043-m borehole drilled to the base of Sermeq Kujalleq (Store Glacier), Greenland. We report substantial but isolated strain heating within interglacial-phase ice at 208 to 242 m depth together with strongly heterogeneous ice deformation in glacial-phase ice below 889 m. We also observe a high-strain interface between glacial- and interglacial-phase ice and a 73-m-thick temperate basal layer, interpreted as locally formed and important for the glacier's fast motion. These findings demonstrate notable spatial heterogeneity, both vertically and at the catchment scale, in the conditions facilitating the fast motion of marine-terminating glaciers in Greenland.Publisher PDFPeer reviewe

Correlation of HPV16 Gene Status and Gene Expression With Antibody Seropositivity and TIL Status in OPSCC.

IntroductionHuman papillomavirus 16 (HPV16) is the main cause of oropharyngeal squamous cell carcinoma (OPSCC). To date, the links between HPV16 gene expression and adaptive immune responses have not been investigated. We evaluated the correlation of HPV16 DNA, RNA transcripts and features of adaptive immune response by evaluating antibody isotypes against E2, E7 antigens and density of tumor-infiltrating lymphocytes (TIL).Material and methodsFFPE-tissue from 27/77 p16-positive OPSCC patients was available. DNA and RNA were extracted and quantified using qPCR for all HPV16 genes. The TIL status was assessed. Immune responses against E2 and E7 were quantified by ELISA (IgG, IgA, and IgM; 77 serum samples pre-treatment, 36 matched post-treatment).ResultsAmounts of HPV16 genes were highly correlated at DNA and RNA levels. RNA co-expression of all genes was detected in 37% (7/19). E7 qPCR results were correlated with higher anti-E7 antibody (IgG, IgA) level in the blood. Patients with high anti-E2 IgG antibody (>median) had better overall survival (p=0.0311); anti-E2 and anti-E7 IgA levels had no detectable effect. During the first 6 months after treatment, IgA but not IgG increased significantly, and >6 months both antibody classes declined over time. Patients with immune cell-rich tumors had higher levels of circulating antibodies against HPV antigens.ConclusionWe describe an HPV16 qPCR assay to quantify genomic and transcriptomic expression and correlate this with serum antibody levels against HPV16 oncoproteins. Understanding DNA/RNA expression, relationship to the antibody response in patients regarding treatment and outcome offers an attractive tool to improve patient care

Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity

Multi-minicore Disease

Multi-minicore Disease (MmD) is a recessively inherited neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown. Marked clinical variability corresponds to genetic heterogeneity: the most instantly recognizable classic phenotype characterized by spinal rigidity, early scoliosis and respiratory impairment is due to recessive mutations in the selenoprotein N (SEPN1) gene, whereas recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement resembling central core disease (CCD). In the latter forms, there may also be a histopathologic continuum with CCD due to dominant RYR1 mutations, reflecting the common genetic background. Pathogenetic mechanisms of RYR1-related MmD are currently not well understood, but likely to involve altered excitability and/or changes in calcium homeoestasis; calcium-binding motifs within the selenoprotein N protein also suggest a possible role in calcium handling. The diagnosis of MmD is based on the presence of suggestive clinical features and multiple cores on muscle biopsy; muscle MRI may aid genetic testing as patterns of selective muscle involvement are distinct depending on the genetic background. Mutational analysis of the RYR1 or the SEPN1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to address the risk of marked respiratory impairment in SEPN1-related MmD and the possibility of malignant hyperthermia susceptibility in RYR1-related forms. In the majority of patients, weakness is static or only slowly progressive, with the degree of respiratory impairment being the most important prognostic factor

Intermittent PI3Ko inhibition sustains anti-tumor immunity and curbs irAEs

YesPhosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity

Research data supporting "Structural controls on the hydrology of crevasses on the Greenland ice sheet"

This dataset contains stress estimations and crevasse and water surface maps across the Store Glacier region of West Greenland from satellite and UAV data. Methods are outlined in the associated paper, and detailed information on the interpretation and use of the data is provided in the README.txt file.This research was funded by the European Research Council as part of the RESPON- DER project under the European Union’s Horizon 2020 research and innovation program (Grant 683043). TRC was supported by a Natural Environment Research Council Doctoral Training Partnership Studentship (Grant NE/L002507/1)