South Atlantic tide gauge data management plan

Develop a harmonised data management plan [D4.2] [NERCNOC] for all South Atlantic tide gauge data building on current international data centre activities

Comments on the Paper “Is the sea level stable at Aden, Yemen?” by Albert Parker and Clifford D. Ollier in Earth Systems and Environment (Volume 1, December 2017)

This short note provides comments and a response to the paper published in Earth Systems and Environment by Albert Parker and Clifford D. Ollier (Volume 1, December 2017) entitled “Is the Sea Level Stable at Aden, Yemen?

What is the pathogenic CAG expansion length in Huntington’s disease?

Huntington’s disease (HD) (OMIM 143100) is caused by an expanded CAG repeat tract in the HTT gene. The inherited CAG length is known to expand further in somatic and germline cells in HD subjects. Age at onset of the disease is inversely correlated with the inherited CAG length, but is further modulated by a series of genetic modifiers which are most likely to act on the CAG repeat in HTT that permit it to further expand. Longer repeats are more prone to expansions, and this expansion is age dependent and tissue-specific. Given that the inherited tract expands through life and most subjects develop disease in mid-life, this implies that in cells that degenerate, the CAG length is likely to be longer than the inherited length. These findings suggest two thresholds – the inherited CAG length which permits further expansion, and the intracellular pathogenic threshold, above which cells become dysfunctional and die. This two-step mechanism has been previously proposed and modelled mathematically to give an intracellular pathogenic threshold at a tract length of 115 CAG (95% confidence intervals 70-165 CAG). Empirically, the intracellular pathogenic threshold is difficult to determine. Clues from studies of people and models of HD, and from other diseases caused by expanded repeat tracts, place this threshold between 60-100 CAG, most likely towards the upper part of that range. We assess this evidence and discuss how the intracellular pathogenic threshold in manifest disease might be better determined. Knowing the cellular pathogenic threshold would be informative for both understanding the mechanism in HD and deploying treatments

Towards comprehensive observing and modeling systems for monitoring and predicting regional to coastal sea level

A major challenge for managing impacts and implementing effective mitigation measures and adaptation strategies for coastal zones affected by future sea level (SL) rise is our limited capacity to predict SL change at the coast on relevant spatial and temporal scales. Predicting coastal SL requires the ability to monitor and simulate a multitude of physical processes affecting SL, from local effects of wind waves and river runoff to remote influences of the large-scale ocean circulation on the coast. Here we assess our current understanding of the causes of coastal SL variability on monthly to multi-decadal timescales, including geodetic, oceanographic and atmospheric aspects of the problem, and review available observing systems informing on coastal SL. We also review the ability of existing models and data assimilation systems to estimate coastal SL variations and of atmosphere-ocean global coupled models and related regional downscaling efforts to project future SL changes. We discuss (1) observational gaps and uncertainties, and priorities for the development of an optimal and integrated coastal SL observing system, (2) strategies for advancing model capabilities in forecasting short-term processes and projecting long-term changes affecting coastal SL, and (3) possible future developments of sea level services enabling better connection of scientists and user communities and facilitating assessment and decision making for adaptation to future coastal SL change.RP was funded by NASA grant NNH16CT00C. CD was supported by the Australian Research Council (FT130101532 and DP 160103130), the Scientific Committee on Oceanic Research (SCOR) Working Group 148, funded by national SCOR committees and a grant to SCOR from the U.S. National Science Foundation (Grant OCE-1546580), and the Intergovernmental Oceanographic Commission of UNESCO/International Oceanographic Data and Information Exchange (IOC/IODE) IQuOD Steering Group. SJ was supported by the Natural Environmental Research Council under Grant Agreement No. NE/P01517/1 and by the EPSRC NEWTON Fund Sustainable Deltas Programme, Grant Number EP/R024537/1. RvdW received funding from NWO, Grant 866.13.001. WH was supported by NASA (NNX17AI63G and NNX17AH25G). CL was supported by NASA Grant NNH16CT01C. This work is a contribution to the PIRATE project funded by CNES (to TP). PT was supported by the NOAA Research Global Ocean Monitoring and Observing Program through its sponsorship of UHSLC (NA16NMF4320058). JS was supported by EU contract 730030 (call H2020-EO-2016, “CEASELESS”). JW was supported by EU Horizon 2020 Grant 633211, Atlantos

Genetic risk underlying psychiatric and cognitive symptoms in Huntington’s Disease

Background Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized exam of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown. Methods We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders, and of intelligence, and testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n=5160) of HD patients. Results Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence. Conclusions Polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Rescue of historical UK sea level charts and ledgers

The main aim of the project was to improve access to historic tide gauge data in our archives. These analogue records have always been available to the general public, but not easily accessible. An enquirer would have to contact us to find out if we held any data of interest before arranging a visit to consult the resource. Making digital copies onsite was difficult, so the numbers were often recorded by hand. These data are unrepeatable scientific measurements and we want to encourage their reuse. Extending back and infilling tide gauge records will help with, among other things, climate change research, storm surge predictions and coastal land movement studies. In 2009, we carried out a pilot project for the Marine Environmental Data and Information Network (MEDIN) and made some historical tide gauge charts and ledgers available online. From April 2012 to March 2013 over 2000 unique visitors accessed these records. Prior to these data being made available, we had 12 requests for analogue data in five years. This is an 83000% increase in requests per year. This shows that placing digitised data online attracts more users and is an important activity. We also wanted to encourage new users, not necessarily from an oceanographic background, such as interested members of the public, to make use of the data. We wanted to create Open Educational Resources (OERs), to raise awareness of BODC and ensure reuse of the data

Real Time Quality Control of Current measurements within MyOcean and Copernicus in situ TAC

An important step within the MyOcean project is to uniform existing Real Time Quality Control (RTQC) and quality assurance procedures of the different nations involved. As the MyOcean service is thought to be available at any time and open to anyone, an agreement in good Real Time Quality Control (RTQC) methods and procedures is vital to guarantee high data quality distributed to users via international exchange. The agreement on the implementation of uniform RTQC procedures have the severe potential to overcome the inconsistency within the existing datasets provided actually by the international community. This document is based upon previous experiences and has the following objectives: - “To ensure the data consistency within a single data set and within a collection of data sets and to ensure that the quality and errors of the data are apparent to the user who has sufficient information to assess its sustainability for a task.” (IOC/IODE, Manuals and Guides 26, 1993). One of the various tasks of the MyOcean project - the Work Package (WP) 15 – deals with the scientific and technical validation of In Situ-TAC (Technical Assembly Centres) products and forms the frame of this document the RTQC procedure for current measurements. WP15 aims to perform operational quality control (QC) of global and regional products as well as to lead scientific assessment validation activities with regional responsibilities. Beside global scale products, regional specifications are performed in the Arctic, the Black Sea, the North-western Shelves, the Baltic Sea, the South-western Shelves and the Mediterranean Sea. It follows therewith the EuroGOOS regional approach, with establishing regional alliances