63 research outputs found

    Sq and EEJ—A Review on the Daily Variation of the Geomagnetic Field Caused by Ionospheric Dynamo Currents

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    Gaia Data Release 3: reflectance spectra of Solar System small bodies

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    Stars and planetary system

    Gaia Early Data Release 3: acceleration of the solar system from Gaia astrometry

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    Stars and planetary system

    Gaia focused product release: radial velocity time series of long-period variables

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    Stars and planetary system

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Local office policy in the context of strategic planning and structural change The case of the London-South East region, circa 1975-1980

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    SIGLEAvailable from British Library Document Supply Centre- DSC:D172073 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Rethinking the metropolis: reconfiguring the governance structures of the twenty-first-century city-region

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    Increasingly, metropolitan planning is challenged by the tensions between the search to become a ‘competitive metropolis' as well as a ‘sustainable metropolis'. Many urban regions struggle with dealing with these complexities on the metropolitan level and try to find bottom-up solutions to balance between the supposed merits of new territorial frames and identities on the metropolitan level and the often local political spaces. Yet, the political strength of metropolitan areas, necessary to design and implement these policies, remains rather weak. The overarching purpose of this special issue is to develop a more robust and rigorous definition of what ‘thinking metropolitan’ means, particularly for five medium-sized city-regions of the early twenty-first century
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