159 research outputs found

    Causality - Complexity - Consistency: Can Space-Time Be Based on Logic and Computation?

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    The difficulty of explaining non-local correlations in a fixed causal structure sheds new light on the old debate on whether space and time are to be seen as fundamental. Refraining from assuming space-time as given a priori has a number of consequences. First, the usual definitions of randomness depend on a causal structure and turn meaningless. So motivated, we propose an intrinsic, physically motivated measure for the randomness of a string of bits: its length minus its normalized work value, a quantity we closely relate to its Kolmogorov complexity (the length of the shortest program making a universal Turing machine output this string). We test this alternative concept of randomness for the example of non-local correlations, and we end up with a reasoning that leads to similar conclusions as in, but is conceptually more direct than, the probabilistic view since only the outcomes of measurements that can actually all be carried out together are put into relation to each other. In the same context-free spirit, we connect the logical reversibility of an evolution to the second law of thermodynamics and the arrow of time. Refining this, we end up with a speculation on the emergence of a space-time structure on bit strings in terms of data-compressibility relations. Finally, we show that logical consistency, by which we replace the abandoned causality, it strictly weaker a constraint than the latter in the multi-party case.Comment: 17 pages, 16 figures, small correction

    Dravet syndrome as epileptic encephalopathy: Evidence from long-term course and neuropathology

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    Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy

    A standardisation framework for bio‐logging data to advance ecological research and conservation

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    Bio‐logging data obtained by tagging animals are key to addressing global conservation challenges. However, the many thousands of existing bio‐logging datasets are not easily discoverable, universally comparable, nor readily accessible through existing repositories and across platforms, slowing down ecological research and effective management. A set of universal standards is needed to ensure discoverability, interoperability and effective translation of bio‐logging data into research and management recommendations. We propose a standardisation framework adhering to existing data principles (FAIR: Findable, Accessible, Interoperable and Reusable; and TRUST: Transparency, Responsibility, User focus, Sustainability and Technology) and involving the use of simple templates to create a data flow from manufacturers and researchers to compliant repositories, where automated procedures should be in place to prepare data availability into four standardised levels: (a) decoded raw data, (b) curated data, (c) interpolated data and (d) gridded data. Our framework allows for integration of simple tabular arrays (e.g. csv files) and creation of sharable and interoperable network Common Data Form (netCDF) files containing all the needed information for accuracy‐of‐use, rightful attribution (ensuring data providers keep ownership through the entire process) and data preservation security. We show the standardisation benefits for all stakeholders involved, and illustrate the application of our framework by focusing on marine animals and by providing examples of the workflow across all data levels, including filled templates and code to process data between levels, as well as templates to prepare netCDF files ready for sharing. Adoption of our framework will facilitate collection of Essential Ocean Variables (EOVs) in support of the Global Ocean Observing System (GOOS) and inter‐governmental assessments (e.g. the World Ocean Assessment), and will provide a starting point for broader efforts to establish interoperable bio‐logging data formats across all fields in animal ecology

    Guidelines for Modeling and Reporting Health Effects of Climate Change Mitigation Actions

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    Background: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers. Objective: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions. Methods: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies. Results: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting. Discussion: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can inform evidence-based decision making and practice

    Seasonality and spatial heterogeneity of the surface ocean carbonate system in the northwest European continental shelf

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    In 2014–5 the UK NERC sponsored an 18 month long Shelf Sea Biogeochemistry research programme which collected over 1500 nutrient and carbonate system samples across the NW European Continental shelf, one of the largest continental shelves on the planet. This involved the cooperation of 10 different Institutes and Universities, using 6 different vessels. Additional carbon dioxide (CO2) data were obtained from the underway systems on three of the research vessels. Here, we present and discuss these data across 9 ecohydrodynamic regions, adapted from those used by the EU Marine Strategy Framework Directive (MSFD). We observed strong seasonal and regional variability in carbonate chemistry around the shelf in relation to nutrient biogeochemistry. Whilst salinity increased (and alkalinity decreased) out from the near-shore coastal waters offshore throughout the year nutrient concentrations varied with season. Spatial and seasonal variations in the ratio of DIC to nitrate concentration were seen that could impact carbon cycling. A decrease in nutrient concentrations and a pronounced under-saturation of surface pCO2 was evident in the spring in most regions, especially in the Celtic Sea. This decrease was less pronounced in Liverpool Bay and to the North of Scotland, where nutrient concentrations remained measurable throughout the year. The near-shore and relatively shallow ecosystems such as the eastern English Channel and southern North Sea were associated with a thermally driven increase in pCO2 to above atmospheric levels in summer and an associated decrease in pH. Non-thermal processes (such as mixing and the remineralisation of organic material) dominated in winter in most regions but especially in the northwest of Scotland and in Liverpool Bay. The large database collected will improve understanding of carbonate chemistry over the North-Western European Shelf in relation to nutrient biogeochemistry, particularly in the context of climate change and ocean acidification

    Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

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    The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-ÎČ PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-ÎČ positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-ÎČ burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

    Prompt K_short production in pp collisions at sqrt(s)=0.9 TeV

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    The production of K_short mesons in pp collisions at a centre-of-mass energy of 0.9 TeV is studied with the LHCb detector at the Large Hadron Collider. The luminosity of the analysed sample is determined using a novel technique, involving measurements of the beam currents, sizes and positions, and is found to be 6.8 +/- 1.0 microbarn^-1. The differential prompt K_short production cross-section is measured as a function of the K_short transverse momentum and rapidity in the region 0 < pT < 1.6 GeV/c and 2.5 < y < 4.0. The data are found to be in reasonable agreement with previous measurements and generator expectations.Comment: 6+18 pages, 6 figures, updated author lis
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