Amplified Sediment waves in the Irish Sea (AmSedIS)

Exceptionally high, straight-crested and trochoidal sediment waves have recently been observed on shelf seas world-wide, and reach heights of up to 36 m in the Irish Sea. It is uncertain how the interplay between geological, biogeochemical and hydrodynamic processes influences the migration and extreme growth of these sediment waves. The AmSedIS project thus sets out to (1) investigate the role of sediment granulometry and sedimentavailability on both “extreme” and “normal” sediment wave development and (2) investigate the potential association of methane derived carbonate formation with extreme sediment wave growth. The preliminary findings are: (1) The crests of unusually high and trochoidal sediment waves still migrate over several meters per year and they consist of coarser, more poorly sorted sediments in comparison to the "normal" sediments waves; (2) Methane seepage is not considered a factor in extreme sediment wave development; (3) The excess of mobile sediment supply seems to allow for "extreme" sediment wave growth, and is linked to palaeo-tunnel valleys and the finer sediments that fill them or with converging sediment transport pathways; (4) The variation in sediment from sediment wave trough to crest to trough will form the basis for more advanced numerical modelling

Seabed geomorphology: a two-part classification system

The BGS has developed a two- part classification system (‘Morphology’ and ‘Geomorphology’) to facilitate work on a new ‘S eabed Geomorphology’ mapping initia tive, and this classification system is the focus of this report. As stated in the Foreword, the rationale and the basic framework of the classification system were conceived and es tablished within BGS, but recent collaboration within the MAREANO -Norway, INFOMAR -Ireland, and MAREMAP -UK (MIM) partnership has led to significant improvement of the classifi cation system, and this report. To further support this effort, existing BGS GIS tools (SIGMA) ha ve been adapted to apply this two-part classification system for more efficient geom orphological mapping in the marine environment. This report: provides a brief background on seabed mapping and characterisation, as well as how this science has been addressed historically within BGS; describes the current motiva tion to conduct seabed geom orphological mapping, and the requirement for a new set of t ools to facilitate this work; describes the logical framework that underpins the classification system; outlines the attributes of the classification system, how it can be applied, and discusses the advantages and limitations of the approach. It is anticipated that through testing and usage, the classification syst em will be revised and improved over time, with updated versions released through MIM partnershi p. It is also planned that a further ‘user guide’ report will be produced for the classifi cation system and the GIS tools, including thematic details (e.g. background information on ‘coastal’ or ‘glacial’ features) and a feature glossary

Phased occupation and retreat of the last British–Irish Ice Sheet in the southern North Sea: geomorphic and seismostratigraphic evidence of a dynamic ice lobe

Along the terrestrial margin of the southern North Sea, previous studies of the MIS 2 glaciation impacting eastern Britain have played a significant role in the development of principles relating to ice sheet dynamics (e.g. deformable beds), and the practice of reconstructing the style, timing, and spatial configuration of palaeo-ice sheets. These detailed terrestrially-based findings have however relied on observations made from only the outer edges of the former ice mass, as the North Sea Lobe (NSL) of the British-Irish Ice Sheet (BIIS) occupied an area that is now almost entirely submarine (c.21–15 ka). Compounded by the fact that marine-acquired data have been primarily of insufficient quality and density, the configuration and behaviour of the last BIIS in the southern North Sea remains surprisingly poorly constrained. This paper presents analysis of a new, integrated set of extensive seabed geomorphological and seismo-stratigraphic observations that both advances the principles developed previously onshore (e.g. multiple advance and retreat cycles), and provides a more detailed and accurate reconstruction of the BIIS at its southern-most extent in the North Sea. A new bathymetry compilation of the region reveals a series of broad sedimentary wedges and associated moraines that represent several terminal positions of the NSL. These former still-stand ice margins (1–4) are also found to relate to newly-identified architectural patterns (shallow stacked sedimentary wedges) in the region's seismic stratigraphy (previously mapped singularly as the Bolders Bank Formation). With ground-truthing constraint provided by sediment cores, these wedges are interpreted as sub-marginal till wedges, formed by complex subglacial accretionary processes that resulted in till thickening towards the former ice-sheet margins. The newly sub-divided shallow seismic stratigraphy (at least five units) also provides an indication of the relative event chronology of the NSL. While there is a general record of south-to-north retreat, seismic data also indicate episodes of ice-sheet re-advance suggestive of an oscillating margin (e.g. MIS 2 maximum not related to first incursion of ice into region). Demonstrating further landform interdependence, geographically-grouped sets of tunnel valleys are shown to be genetically related to these individual ice margins, providing clear insight into how meltwater drainage was organised at the evolving termini of this dynamic ice lobe. The newly reconstructed offshore ice margins are found to be well correlated with previously observed terrestrial limits in Lincolnshire and E. Yorkshire (Holderness) (e.g. MIS 2 maximum and Withernsea Till). This reconstruction will hopefully provide a useful framework for studies targeting the climatic, mass-balance, and external glaciological factors (i.e. Fennoscandian Ice Sheet) that influenced late-stage advance and deglaciation, important for accurately characterising both modern and palaeo-ice sheets

Drilling-induced and logging-related features illustrated from IODP-ICDP Expedition 364 downhole logs and borehole imaging tools

Expedition 364 was a joint IODP and ICDP mission-specific platform (MSP) expedition to explore the Chicxulub impact crater buried below the surface of the Yucatán continental shelf seafloor. In April and May 2016, this expedition drilled a single borehole at Site M0077 into the crater's peak ring. Excellent quality cores were recovered from ~ 505 to ~1335m below seafloor (m b.s.f.), and high-resolution open hole logs were acquired between the surface and total drill depth. Downhole logs are used to image the borehole wall, measure the physical properties of rocks that surround the borehole, and assess borehole quality during drilling and coring operations. When making geological interpretations of downhole logs, it is essential to be able to distinguish between features that are geological and those that are operation-related. During Expedition 364 some drilling-induced and logging-related features were observed and include the following: effects caused by the presence of casing and metal debris in the hole, logging-tool eccentering, drilling-induced corkscrew shape of the hole, possible re-magnetization of low-coercivity grains within sedimentary rocks, markings on the borehole wall, and drilling-induced changes in the borehole diameter and trajectory

Ocean Drilling Perspectives on Meteorite Impacts

Extraterrestrial impacts that reshape the surfaces of rocky bodies are ubiquitous in the solar system. On early Earth, impact structures may have nurtured the evolution of life. More recently, a large meteorite impact off the Yucatán Peninsula in Mexico at the end of the Cretaceous caused the disappearance of 75% of species known from the fossil record, including non-avian dinosaurs, and cleared the way for the dominance of mammals and the eventual evolution of humans. Understanding the fundamental processes associated with impact events is critical to understanding the history of life on Earth, and the potential for life in our solar system and beyond. Scientific ocean drilling has generated a large amount of unique data on impact pro- cesses. In particular, the Yucatán Chicxulub impact is the single largest and most sig- nificant impact event that can be studied by sampling in modern ocean basins, and marine sediment cores have been instrumental in quantifying its environmental, cli- matological, and biological effects. Drilling in the Chicxulub crater has significantly advanced our understanding of fundamental impact processes, notably the formation of peak rings in large impact craters, but these data have also raised new questions to be addressed with future drilling. Within the Chicxulub crater, the nature and thickness of the melt sheet in the central basin is unknown, and an expanded Paleocene hemipelagic section would provide insights to both the recovery of life and the climatic changes that followed the impact. Globally, new cores collected from today’s central Pacific could directly sample the downrange ejecta of this northeast-southwest trending impact. Extraterrestrial impacts have been controversially suggested as primary drivers for many important paleoclimatic and environmental events throughout Earth history. However, marine sediment archives collected via scientific ocean drilling and geo- chemical proxies (e.g., osmium isotopes) provide a long-term archive of major impact events in recent Earth history and show that, other than the end-Cretaceous, impacts do not appear to drive significant environmental changes

Combined impact of lipidomic and genetic aberrations on clinical outcomes in metastatic castration-resistant prostate cancer

Background: Both changes in circulating lipids represented by a validated poor prognostic 3-lipid signature (3LS) and somatic tumour genetic aberrations are individually associated with worse clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). A key question is how the lipid environment and the cancer genome are interrelated in order to exploit this therapeutically. We assessed the association between the poor prog‑ nostic 3-lipid signature (3LS), somatic genetic aberrations and clinical outcomes in mCRPC. Methods: We performed plasma lipidomic analysis and cell-free DNA (cfDNA) sequencing on 106 men with mCRPC commencing docetaxel, cabazitaxel, abiraterone or enzalutamide (discovery cohort) and 94 men with mCRPC com‑ mencing docetaxel (validation cohort). Diferences in lipid levels between men ± somatic genetic aberrations were assessed with t-tests. Associations between the 3LS and genetic aberrations with overall survival (OS) were examined using Kaplan-Meier methods and Cox proportional hazard models. Results: The 3LS was associated with shorter OS in the discovery (hazard ratio [HR] 2.15, 95% confdence interval [CI] 1.4-3.3, p < 0.001) and validation cohorts (HR 2.32, 95% CI 1.59–3.38, p < 0.001). Elevated plasma sphingolipids were associated with AR, TP53, RB1 and PI3K aberrations (p < 0.05). Men with both the 3LS and aberrations in AR, TP53, RB1 or PI3K had shorter OS than men with neither in both cohorts (p ≤ 0.001). The presence of 3LS and/or genetic aberration was independently associated with shorter OS for men with AR, TP53, RB1 and PI3K aberrations (p < 0.02). Furthermore, aggressive-variant prostate cancer (AVPC), defned as 2 or more aberrations in TP53, RB1 and/or PTEN, was associated with elevated sphingolipids. The combination of AVPC and 3LS predicted for a median survival of ~12 months. The relatively small sample size of the cohorts limits clinical applicability and warrants future studies. Conclusions: Elevated circulating sphingolipids were associated with AR, TP53, RB1, PI3K and AVPC aberrations in mCRPC, and the combination of lipid and genetic abnormalities conferred a worse prognosis. These fndings suggest that certain genotypes in mCRPC may beneft from metabolic therapies.Blossom Mak ... Lisa M. Butler ... et. a

Early paleocene paleoceanography and export productivity in the Chicxulub crater

The Chicxulub impact caused a crash in productivity in the world''s oceans which contributed to the extinction of ~75% of marine species. In the immediate aftermath of the extinction, export productivity was locally highly variable, with some sites, including the Chicxulub crater, recording elevated export production. The long-term transition back to more stable export productivity regimes has been poorly documented. Here, we present elemental abundances, foraminifer and calcareous nannoplankton assemblage counts, total organic carbon, and bulk carbonate carbon isotope data from the Chicxulub crater to reconstruct changes in export productivity during the first 3 Myr of the Paleocene. We show that export production was elevated for the first 320 kyr of the Paleocene, declined from 320 kyr to 1.2 Myr, and then remained low thereafter. A key interval in this long decline occurred 900 kyr to 1.2 Myr post impact, as calcareous nannoplankton assemblages began to diversify. This interval is associated with fluctuations in water column stratification and terrigenous flux, but these variables are uncorrelated to export productivity. Instead, we postulate that the turnover in the phytoplankton community from a post-extinction assemblage dominated by picoplankton (which promoted nutrient recycling in the euphotic zone) to a Paleocene pelagic community dominated by relatively larger primary producers like calcareous nannoplankton (which more efficiently removed nutrients from surface waters, leading to oligotrophy) is responsible for the decline in export production in the southern Gulf of Mexico. © 2021. American Geophysical Union. All Rights Reserved

Overcoming enzalutamide resistance in metastatic prostate cancer by targeting sphingosine kinase

Background Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20–30% of men with metastatic castration-resistant prostate cancer (mCRPC). Ceramide metabolism may have a role in ARSI resistance. Our study's aim is to investigate the association of the ceramide-sphingosine-1-phosphate (ceramide-S1P) signalling axis with ARSI resistance in mCRPC. Methods Lipidomic analysis (∼700 lipids) was performed on plasma collected from 132 men with mCRPC, before commencing enzalutamide or abiraterone. AR gene aberrations in 77 of these men were identified by deep sequencing of circulating tumour DNA. Associations between circulating lipids, radiological progression-free survival (rPFS) and overall survival (OS) were examined by Cox regression. Inhibition of ceramide-S1P signalling with sphingosine kinase (SPHK) inhibitors (PF-543 and ABC294640) on enzalutamide efficacy was investigated with in vitro assays, and transcriptomic and lipidomic analyses of prostate cancer (PC) cell lines (LNCaP, C42B, 22Rv1). Findings Men with elevated circulating ceramide levels had shorter rPFS (HR=2·3, 95% CI=1·5–3·6, p = 0·0004) and shorter OS (HR=2·3, 95% CI=1·4–36, p = 0·0005). The combined presence of an AR aberration with elevated ceramide levels conferred a worse prognosis than the presence of only one or none of these characteristics (median rPFS time = 3·9 vs 8·3 vs 17·7 months; median OS time = 8·9 vs 19·8 vs 34·4 months). SPHK inhibitors enhanced enzalutamide efficacy in PC cell lines. Transcriptomic and lipidomic analyses indicated that enzalutamide combined with SPHK inhibition enhanced PC cell death by SREBP-induced lipotoxicity. Interpretation Ceramide-S1P signalling promotes ARSI resistance, which can be reversed with SPHK inhibitors.Hui-Ming Lin, Blossom Mak, Nicole Yeung, Kevin Huynh, Thomas G. Meikl, Natalie A. Mellett, Edmond M. Kwan, Heidi Fettk, Ben Tran, Ian D. Davis, Kate L. Mahon, Alison Zhang, Martin R. Stockler, Karen Brisco, Gavin Marx, Megan Crumbaker, Phillip D. Stricker, Pan Du, Jianjun Yu, Shidong Ji, Tahlia Scheinberg, Michael Fitzpatrick, Paul Bonnitcha, David R. Sullivan, Anthony M. Joshua, Arun A. Azad, Lisa M. Butler, Peter J. Meikle, Lisa G. Horvat

The effects of long-term saturated fat enriched diets on the brain lipidome

The brain is highly enriched in lipids, where they influence neurotransmission, synaptic plasticity and inflammation. Non-pathological modulation of the brain lipidome has not been previously reported and few studies have investigated the interplay between plasma lipid homeostasis relative to cerebral lipids. This study explored whether changes in plasma lipids induced by chronic consumption of a well-tolerated diet enriched in saturated fatty acids (SFA) was associated with parallel changes in cerebral lipid homeostasis. Male C57Bl/6 mice were fed regular chow or the SFA diet for six months. Plasma, hippocampus (HPF) and cerebral cortex (CTX) lipids were analysed by LC-ESI-MS/MS. A total of 348 lipid species were determined, comprising 25 lipid classes. The general abundance of HPF and CTX lipids was comparable in SFA fed mice versus controls, despite substantial differences in plasma lipid-class abundance. However, significant differences in 50 specific lipid species were identified as a consequence of SFA treatment, restricted to phosphatidylcholine (PC), phosphatidylethanolamine (PE), alkyl-PC, alkenyl-PC, alkyl-PE, alkenyl-PE, cholesterol ester (CE), diacylglycerol (DG), phosphatidylinositol (PI) and phosphatidylserine (PS) classes. Partial least squares regression of the HPF/CTX lipidome versus plasma lipidome revealed the plasma lipidome could account for a substantial proportion of variation. The findings demonstrate that cerebral abundance of specific lipid species is strongly associated with plasma lipid homeostasis

Intravesical Treatments of Bladder Cancer: Review

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy