Preconditioning and triggering of offshore slope failures and turbidity currents revealed by most detailed monitoring yet at a fjord-head delta

Rivers and turbidity currents are the two most important sediment transport processes by volume on Earth. Various hypotheses have been proposed for triggering of turbidity currents offshore from river mouths, including direct plunging of river discharge, delta mouth bar flushing or slope failure caused by low tides and gas expansion, earthquakes and rapid sedimentation. During 2011, 106 turbidity currents were monitored at Squamish Delta, British Columbia. This enables statistical analysis of timing, frequency and triggers. The largest peaks in river discharge did not create hyperpycnal flows. Instead, delayed delta-lip failures occurred 8–11 h after flood peaks, due to cumulative delta top sedimentation and tidally-induced pore pressure changes. Elevated river discharge is thus a significant control on the timing and rate of turbidity currents but not directly due to plunging river water. Elevated river discharge and focusing of river discharge at low tides cause increased sediment transport across the delta-lip, which is the most significant of all controls on flow timing in this setting

Hybrid turbidite-drift channel complexes: An integrated multiscale model

The interaction of deep-marine bottom currents with episodic, unsteady sediment gravity flows affects global sediment transport, forms climate archives, and controls the evolution of continental slopes. Despite their importance, contradictory hypotheses for reconstructing past flow regimes have arisen from a paucity of studies and the lack of direct monitoring of such hybrid systems. Here, we address this controversy by analyzing deposits, high-resolution seafloor data, and near-bed current measurements from two sites where eastward-flowing gravity flows interact(ed) with northward-flowing bottom currents. Extensive seismic and core data from offshore Tanzania reveal a 1650-m-thick asymmetric hybrid channel levee-drift system, deposited over a period of ∼20 m.y. (Upper Cretaceous to Paleocene). High-resolution modern seafloor data from offshore Mozambique reveal similar asymmetric channel geometries, which are related to northward-flowing near-bed currents with measured velocities of up to 1.4 m/s. Higher sediment accumulation occurs on the downstream flank of channel margins (with respect to bottom currents), with inhibited deposition or scouring on the upstream flank (where velocities are highest). Toes of the drift deposits, consisting of thick laminated muddy siltstone, which progressively step back into the channel axis over time, result in an interfingering relationship with the sandstone-dominated channel fill. Bottom-current flow directions contrast with those of previous models, which lacked direct current measurements or paleoflow indicators. We finally show how large-scale depositional architecture is built through the temporally variable coupling of these two globally important sediment transport processes. Our findings enable more-robust reconstructions of past oceanic circulation and diagnosis of ancient hybrid turbidite-drift systems

Immunohistochemical detection improves the prognostic value of lymphatic and blood vessel invasion in primary ductal breast cancer

Background<p></p> Lymphovascular invasion (LBVI) including lymphatic (LVI) and blood (BVI) vessel invasion is a critical step in cancer metastasis. In breast cancer, the optimal detection method of LBVI remains unclear. This research aimed to compare the prognostic value of different assessments of the LVI and BVI in patients with early breast cancer.<p></p> Methods<p></p> The study cohort included 360 patients with a median follow-up of 168 months. LBVI on H&E sections (LBVIH&E) was reviewed centrally and blinded to the pathology report. Immunohistochemical staining for D2-40 and Factor VIII was performed to identify LVID2–40 and BVIFVIII.<p></p> Results<p></p> LBVIH&E, LVID2–40 and BVIFVIII were present in 102 (28%), 127 (35%) and 59 (16%) patients respectively. In node-negative patients (206), LBVIH&E, LVID2–40 and BVIFVIII were present in 41 (20%), 53 (26%) and 21 (10%) respectively. In triple-negative patients (120), LBVIH&E, LVID2–40 and BVIFVIII were present in 35 (29%), 46 (38%) and 16 (13%) respectively. LBVIH&E was significantly associated with tumour recurrence in the whole cohort (P < 0.001), node-negative patients (P = 0.001) and triple-negative patients (P = 0.004). LVID2–40 and BVIFVIII were significantly associated with tumour recurrence in whole cohort, node-negative (all P < 0.001) and triple-negative patients (P = 0.002). In multivariate survival analysis, only LVID2–40 and BVIFVIII were independent predictors of cancer specific survival in the whole cohort (P = 0.023 and P < 0.001 respectively), node-negative patients (P = 0.004 and P = 0.001 respectively) and triple-negative patients (P = 0.014 and P = 0.001 respectively).<p></p> Conclusion<p></p> Assessment of LVI and BVI by IHC using D2-40 and Factor VIII improves prediction of outcome in patients with node-negative and triple-negative breast cancer

Characterisation of weak layers, physical controls on their global distribution and their role in submarine landslide formation

Submarine landslides pose a hazard to coastal communities as they can generate powerful tsunamis, and threaten critical offshore infrastructure such as seafloor cable networks that underpin global communications. Such events can be orders of magnitude larger than their onshore equivalents. Despite the hazard they pose, many aspects of submarine landslides remain poorly understood, such as why they fail on low angle (<2°), seemingly stable slopes. Many studies have proposed that failure on low slope angles, and the large areal extent of submarine landslides, may be controlled by the presence of laterally-extensive weak layers embedded within the slope stratigraphy, which precondition slopes to failure. Little remains known, however, about the characteristics and processes that control and form weak layers. We conducted a comprehensive review of published submarine landslide studies that examine failure planes and apparent weak layers associated with historical and ancient submarine landslides. Based on a new global landslide catalogue that comprises 64 case studies, this review aims to investigate the types of sediment that form weak layers and to understand the controls on their global variability. Existing classification schemes are based on mechanical process(es), and do not readily enable a diagnosis of weak layers from unfailed sediments. Here, a new and complementary classification of weak layers based on lithology is introduced. This classification enables weak layer recognition from sediment cores (including those sampling unfailed sediments), and allows us to attribute failure mechanisms to different environmental settings where distinct types of weak layers are more likely. The results show that failure planes usually form in the vicinity of an interface between distinct lithologies that together comprise a weak layer. The weak layers of 22 of the 64 case studies were related to characteristic sediment sequences within the slope stratigraphy, of which 19 were classified based on direct measurements from sediment cores and in-situ measurements: 16 weak layers were classified as siliciclastic, four as volcaniclastic, and two as fossiliferous sediment sequences. Only three submarine landsides were related to clay-dominated weak layers. In addition, failure along lithological contrasts was inferred for six case studies. Based on global depositional models likely locations of these different types of weak layer can be inferred. These include oceanic gateways where long-term circulation can create distinct permeability interfaces within siliciclastic sequences, areas of high productivity where biogenic sediments may dominate, and regions that experience widespread ash fall from volcanic eruptions. We highlight that many submarine landslide studies have historically not collected sediment cores that characterise weak layers within intact sedimentary sequences and instead have focused on characterising the slope failure deposit. As weak layers can collapse or become heavily modified during failure, there is a widespread omission of key information required for geotechnical analysis to determine where and why certain slopes are predisposed to failure. We conclude by highlighting the need to combine detailed geotechnical measurements with sedimentological and geophysical analyses including grain-scale observations (e.g. micro-Computed Tomography 3D imagery), and emphasise the importance of a uniform workflow that will allow for a better comparison between individual studies

Direct monitoring of active geohazards: emerging geophysical tools for deep-water assessments

Seafloor networks of cables, pipelines, and other infrastructure underpin our daily lives, providing communication links, information, and energy supplies. Despite their global importance, these networks are vulnerable to damage by a number of natural seafloor hazards, including landslides, turbidity currents, fluid flow, and scour. Conventional geophysical techniques, such as high-resolution reflection seismic and side-scan sonar, are commonly employed in geohazard assessments. These conventional tools provide essential information for route planning and design; however, such surveys provide only indirect evidence of past processes and do not observe or measure the geohazard itself. As such, many numerical-based impact models lack field-scale calibration, and much uncertainty exists about the triggers, nature, and frequency of deep-water geohazards. Recent advances in technology now enable a step change in their understanding through direct monitoring. We outline some emerging monitoring tools and how they can quantify key parameters for deepwater geohazard assessment. Repeat seafloor surveys in dynamic areas show that solely relying on evidence from past deposits can lead to an under-representation of the geohazard events. Acoustic Doppler current profiling provides new insights into the structure of turbidity currents, whereas instrumented mobile sensors record the nature of movement at the base of those flows for the first time. Existing and bespoke cabled networks enable high bandwidth, low power, and distributed measurements of parameters such as strain across large areas of seafloor. These techniques provide valuable new measurements that will improve geohazard assessments and should be deployed in a complementary manner alongside conventional geophysical tools

Chronology Protection in Galileon Models and Massive Gravity

Galileon models are a class of effective field theories that have recently received much attention. They arise in the decoupling limit of theories of massive gravity, and in some cases they have been treated in their own right as scalar field theories with a specific nonlinearly realized global symmetry (Galilean transformation). It is well known that in the presence of a source, these Galileon theories admit superluminal propagating solutions, implying that as quantum field theories they must admit a different notion of causality than standard local Lorentz invariant theories. We show that in these theories it is easy to construct closed timelike curves (CTCs) within the {\it naive} regime of validity of the effective field theory. However, on closer inspection we see that the CTCs could never arise since the Galileon inevitably becomes infinitely strongly coupled at the onset of the formation of a CTC. This implies an infinite amount of backreaction, first on the background for the Galileon field, signaling the break down of the effective field theory, and subsequently on the spacetime geometry, forbidding the formation of the CTC. Furthermore the background solution required to create CTCs becomes unstable with an arbitrarily fast decay time. Thus Galileon theories satisfy a direct analogue of Hawking's chronology protection conjecture.Comment: 34 pages, no figure

de Sitter Galileon

We generalize the Galileon symmetry and its relativistic extension to a de Sitter background. This is made possible by studying a probe-brane in a flat five-dimensional bulk using a de Sitter slicing. The generalized Lovelock invariants induced on the probe brane enjoy the induced Poincar\'e symmetry inherited from the bulk, while living on a de Sitter geometry. The non-relativistic limit of these invariants naturally maintain a generalized Galileon symmetry around de Sitter while being free of ghost-like pathologies. We comment briefly on the cosmology of these models and the extension to the AdS symmetry as well as generic FRW backgrounds

A drug repurposing screen for whipworms informed by comparative genomics.

Hundreds of millions of people worldwide are infected with the whipworm Trichuris trichiura. Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these ex vivo by assessing motility of adult worms of Trichuris muris, the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC50 values of ≤50 μM against T. muris ex vivo, and selected nine for testing in vivo. However, the best worm burden reduction seen in mice was just 19%. The high number of ex vivo hits against T. muris shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug development against whipworms

Electron Bio-Imaging Centre (eBIC): the UK national research facility for biological electron microscopy

The recent resolution revolution in cryo-EM has led to a massive increase in demand for both time on high-end cryo-electron microscopes and access to cryo-electron microscopy expertise. In anticipation of this demand, eBIC was set up at Diamond Light Source in collaboration with Birkbeck College London and the University of Oxford, and funded by the Wellcome Trust, the UK Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC) to provide access to high-end equipment through peer review. eBIC is currently in its start-up phase and began by offering time on a single FEI Titan Krios microscope equipped with the latest generation of direct electron detectors from two manufacturers. Here, the current status and modes of access for potential users of eBIC are outlined. In the first year of operation, 222 d of microscope time were delivered to external research groups, with 95 visits in total, of which 53 were from unique groups. The data collected have generated multiple high- to intermediate-resolution structures (2.8–8 Å), ten of which have been published. A second Krios microscope is now in operation, with two more due to come online in 2017. In the next phase of growth of eBIC, in addition to more microscope time, new data-collection strategies and sample-preparation techniques will be made available to external user groups. Finally, all raw data are archived, and a metadata catalogue and automated pipelines for data analysis are being developed

The Crystallography of Color Superconductivity

We develop the Ginzburg-Landau approach to comparing different possible crystal structures for the crystalline color superconducting phase of QCD, the QCD incarnation of the Larkin-Ovchinnikov-Fulde-Ferrell phase. In this phase, quarks of different flavor with differing Fermi momenta form Cooper pairs with nonzero total momentum, yielding a condensate that varies in space like a sum of plane waves. We work at zero temperature, as is relevant for compact star physics. The Ginzburg-Landau approach predicts a strong first-order phase transition (as a function of the chemical potential difference between quarks) and for this reason is not under quantitative control. Nevertheless, by organizing the comparison between different possible arrangements of plane waves (i.e. different crystal structures) it provides considerable qualitative insight into what makes a crystal structure favorable. Together, the qualitative insights and the quantitative, but not controlled, calculations make a compelling case that the favored pairing pattern yields a condensate which is a sum of eight plane waves forming a face-centered cubic structure. They also predict that the phase is quite robust, with gaps comparable in magnitude to the BCS gap that would form if the Fermi momenta were degenerate. These predictions may be tested in ultracold gases made of fermionic atoms. In a QCD context, our results lay the foundation for a calculation of vortex pinning in a crystalline color superconductor, and thus for the analysis of pulsar glitches that may originate within the core of a compact star.Comment: 41 pages, 13 figures, 1 tabl