Eruptive activity of the Santorini Volcano controlled by sea-level rise and fall

Sea-level change is thought to influence the frequencies of volcanic eruptions on glacial to interglacial timescales. However, the underlying physical processes and their importance relative to other influences (for example, magma recharge rates) remain poorly understood. Here we compare an approximately 360-kyr-long record of effusive and explosive eruptions from the flooded caldera volcano at Santorini (Greece) with a high-resolution sea-level record spanning the last four glacial–interglacial cycles. Numerical modelling shows that when the sea level falls by 40 m below the present-day level, the induced tensile stresses in the roof of the magma chamber of Santorini trigger dyke injections. As the sea level continues to fall to −70 or −80 m, the induced tensile stress spreads throughout the roof so that some dykes reach the surface to feed eruptions. Similarly, the volcanic activity gradually disappears after the sea level rises above −40 m. Synchronizing Santorini’s stratigraphy with the sea-level record using tephra layers in marine sediment cores shows that 208 out of 211 eruptions (both effusive and explosive) occurred during periods constrained by sea-level falls (below −40 m) and subsequent rises, suggesting a strong absolute sea-level control on the timing of eruptions on Santorini—a result that probably applies to many other volcanic islands around the world

The Met Office Unified Model Global Atmosphere 6.0/6.1 and JULES Global Land 6.0/6.1 configurations

We describe Global Atmosphere 6.0 and Global Land 6.0: the latest science configurations of the Met Office Unified Model and JULES land surface model developed for use across all timescales. Global Atmosphere 6.0 includes the ENDGame dynamical core, which significantly increases mid-latitude variability improving a known model bias. Alongside developments of the model’s physical parametrisations, ENDGame also increases variability in the tropics, which leads to an improved representation of tropical cyclones and other tropical phenomena. Further developments of the atmospheric and land surface parametrisations improve other aspects of model performance, including the forecasting of surface weather phenomena. We also describe Global Atmosphere 6.1 and Global Land 6.1, which include a small number of long-standing differences from our main trunk configurations that we continue to require for operational global weather prediction. Since July 2014, GA6.1/GL6.1 has been used by the Met Office for operational global NWP, whilst GA6.0/GL6.0 was implemented in its remaining global prediction systems over the following year

Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype

Amyotrophic lateral sclerosis (ALS) is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs). We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes) was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years) sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18). Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033). We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025). Our data are consistent with an oligogenic model of ALS. We provide evidence for a number of entirely novel genetic variants of ALS caused by mutations in RNA-binding proteins. Moreover we show that these mutations act synergistically with each other and with C9ORF72 expansions to modify the clinical phenotype of ALS. A key finding is that this synergy is present only between functionally interacting variants. This work has significant implications for ALS therapy development

The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

How do women seeking abortion choose between surgical and medical abortion? Perspectives from abortion service providers

BACKGROUND: Depending on availability, many Australian women seeking an abortion will be faced with the choice between surgical or medical abortion. Little is known about the factors that influence Australian women's choice of method. AIM: Through the perspectives of abortion service providers, this study aimed to explore the factors that contribute to Australian women's decision to have a surgical or medical abortion. MATERIALS AND METHODS: In 2015, in-depth interviews were conducted with fifteen Victorian-based key informants (KIs) directly providing or working within a service offering medical abortion. Ten KIs were working at a service that also provided surgical abortion. Interviews were semi-structured, conducted face-to-face or over the telephone, transcribed verbatim and analysed thematically. RESULTS: KIs described varying levels of awareness of medical abortion, with poorer awareness in regional areas. When it comes to accessing information, women were informed by: their own research (often online); their own experiences and the experiences of others; and advice from health professionals. Women's reasons for choosing surgical or medical abortion range from the pragmatic (timing and location of the method, support at home) to the subjective (perceived risk, emotional impact, privacy, control, and physical ability). CONCLUSIONS: Women benefit from an alternative to surgical abortion and are well-placed to choose between the two methods, however, challenges remain to ensure that all women are enabled to make an informed choice. KIs identify the need to: promote the availability of medical abortion; address misconceptions about this method; and increase general practitioner involvement in the provision of medical abortion

\u27…a one stop shop in their own community\u27: medical abortion and the role of general practice

BACKGROUND: The introduction to Australia of modern medical abortion methods, which require less specialist expertise and equipment than the more traditional surgical methods, have brought an as yet unrealised potential to improve access to abortion services. AIMS: To investigate the potential for expanding the role of general practice in the provision of medical abortion in Victoria. MATERIALS AND METHODS: In 2015, in-depth interviews were conducted with 19 experts in abortion service provision in Victoria. A semi-structured interview schedule was used to guide the interviews. Interviews were transcribed verbatim and transcripts analysed thematically. RESULTS: Participants were largely very supportive of the provision of early medical abortion in general practice as a way of increasing abortion access for women, particularly in rural and regional communities. Access to abortion was seen as an essential component of women's comprehensive health care and therefore general practitioners (GPs) were perceived as ideally placed to provide this service. However, this would require development and implementation of new service models, careful consideration of GP and nurse roles, strengthening of partnerships with other health professionals and services in the community, and enhanced training, support and mentoring for clinicians. CONCLUSION: The application of these findings by relevant health services and agencies has the potential to increase provision of medical abortion services in general practice settings, better meeting the health-care needs of women seeking this service