Re-evaluation and extension of the Marine Isotope Stage 5 tephrostratigraphy of the Faroe Islands region: The cryptotephra record

PMA, SMD, WENA and NJGP are supported by NERC through the SMART project (NE/F020600/1, NE/F02116X/1, NE/F021445/1). The research leading to the results for the MIS 4 and 5a tephra horizons has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement n° [259253]. PMA, SMD and NJGP acknowledge the support of the Climate Change Consortium of Wales (C3W). JB is funded by the Research Council of Norway through the INTERACT project (project no. 221999).Abstract Previous studies of marine sequences from the Faroe Islands region have identified a series of coarse-grained tephra horizons deposited during Marine Isotope Stage (MIS) 5. Here we reassess the MIS 5 tephrostratigraphy of the Faroe Islands region and focus on the cryptotephra deposits preserved within the fine-grained fraction of marine core LINK 16. We also extend the record to encompass the late MIS 6 and early MIS 4 periods. A density separation technique, commonly used for tephra investigations in lacustrine settings but rarely applied to marine sediments, is utilised to explore the fine-grained material and EPMA and LA-ICP-MS are employed to determine the major and trace element composition of individual tephra shards. In total, 3 basaltic and 3 rhyolitic Icelandic cryptotephra deposits with homogeneous geochemical compositions are identified — all of which have the potential to act as isochronous tie-lines. Geochemical results highlight that the Grímsvötn volcanic system of Iceland is the predominant source of the basaltic horizons and the Öraefajökull or Torfajökull systems are the likely sources of the rhyolitic deposits. Three of the horizons have been previously recognised in Faroe Islands region marine sequences, with two of these deposits traceable into a Norwegian Sea sequence. An early MIS 4 rhyolitic horizon is the most widespread deposit as it can be traced into the Norwegian Sea and to the south into a record from the Rockall Trough. Basaltic and rhyolitic horizons deposited during late MIS 6 have not been recognised in other sequences and represent new additions to the regional tephrostratigraphy.Publisher PDFPeer reviewe

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Renormalization group flows and continual Lie algebras

We study the renormalization group flows of two-dimensional metrics in sigma models and demonstrate that they provide a continual analogue of the Toda field equations based on the infinite dimensional algebra G(d/dt;1). The resulting Toda field equation is a non-linear generalization of the heat equation, which is integrable in target space and shares the same dissipative properties in time. We provide the general solution of the renormalization group flows in terms of free fields, via Backlund transformations, and present some simple examples that illustrate the validity of their formal power series expansion in terms of algebraic data. We study in detail the sausage model that arises as geometric deformation of the O(3) sigma model, and give a new interpretation to its ultra-violet limit by gluing together two copies of Witten's two-dimensional black hole in the asymptotic region. We also provide some new solutions that describe the renormalization group flow of negatively curved spaces in different patches, which look like a cane in the infra-red region. Finally, we revisit the transition of a flat cone C/Z_n to the plane, as another special solution, and note that tachyon condensation in closed string theory exhibits a hidden relation to the infinite dimensional algebra G(d/dt;1) in the regime of gravity. Its exponential growth holds the key for the construction of conserved currents and their systematic interpretation in string theory, but they still remain unknown.Comment: latex, 73pp including 14 eps fig

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy

The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma

Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk