27 research outputs found

    Putting the geology back into Earth models

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    New digital methods for data capture can now provide photorealistic, spatially precise, and geometrically accurate three-dimensional (3-D) models of rocks exposed at the Earth's surface [Xu et al., 2000; Pringle et al., 2001; Clegg et al., 2005]. These “virtual outcrops” have the potential to create a new form of laboratory-based teaching aids for geoscience students, to help address accessibility issues in fieldwork, and generally to improve public awareness of the spectacular nature of geologic exposures from remote locations worldwide. This article addresses how virtual outcrops can provide calibration, or a quantitative “reality check,” for a new generation of high-resolution predictive models for the Earth's subsurface

    The Iceland Microcontinent and a continental Greenland-Iceland-Faroe Ridge

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    The breakup of Laurasia to form the Northeast Atlantic Realm was the culmination of a long period of tectonic unrest extending back to the Late Palaeozoic. Breakup was prolonged and complex and disintegrated an inhomogeneous collage of cratons sutured by cross-cutting orogens. Volcanic rifted margins formed, which are blanketed by lavas and underlain variously by magma-inflated, extended continental crust and mafic high-velocity lower crust of ambiguous and probably partly continental provenance. New rifts formed by diachronous propagation along old zones of weakness. North of the Greenland-Iceland-Faroe Ridge the newly forming rift propagated south along the Caledonian suture. South of the Greenland-Iceland-Faroe Ridge it propagated north through the North Atlantic Craton along an axis displaced ~ 150 km to the west of the northern rift. Both propagators stalled where the confluence of the Nagssugtoqidian and Caledonian orogens formed a transverse barrier. Thereafter, the ~ 400-km-wide latitudinal zone between the stalled rift tips extended in a distributed, unstable manner along multiple axes of extension that frequently migrated or jumped laterally with shearing occurring between them in diffuse transfer zones. This style of deformation continues to the present day. It is the surface expression of underlying magma-assisted stretching of ductile mid- and lower continental crust which comprises the Icelandic-type lower crust that underlies the Greenland-Iceland-Faroe Ridge. This, and probably also one or more full-crustal-thickness microcontinents incorporated in the Ridge, are capped by surface lavas. The Greenland-Iceland-Faroe Ridge thus has a similar structure to some zones of seaward-dipping reflectors. The contemporaneous melt layer corresponds to the 3–10 km thick Icelandic-type upper crust plus magma emplaced in the ~ 10–30-km-thick Icelandic-type lower crust. This model can account for seismic and gravity data that are inconsistent with a gabbroic composition for Icelandic-type lower crust, and petrological data that show no reasonable temperature or source composition could generate the full ~ 40-km thickness of Icelandic-type crust observed. Numerical modeling confirms that extension of the continental crust can continue for many tens of Myr by lower-crustal flow from beneath the adjacent continents. Petrological estimates of the maximum potential temperature of the source of Icelandic lavas are up to 1450 °C, no more than ~ 100 °C hotter than MORB source. The geochemistry is compatible with a source comprising hydrous peridotite/pyroxenite with a component of continental mid- and lower crust. The fusible petrology, high source volatile contents, and frequent formation of new rifts can account for the true ~ 15–20 km melt thickness at the moderate temperatures observed. A continuous swathe of magma-inflated continental material beneath the 1200-km-wide Greenland-Iceland-Faroe Ridge implies that full continental breakup has not yet occurred at this latitude. Ongoing tectonic instability on the Ridge is manifest in long-term tectonic disequilibrium on the adjacent rifted margins and on the Reykjanes Ridge, where southerly migrating propagators that initiate at Iceland are associated with diachronous swathes of unusually thick oceanic crust. Magmatic volumes in the NE Atlantic Realm have likely been overestimated and the concept of a monogenetic North Atlantic Igneous Province needs to be reappraised. A model of complex, piecemeal breakup controlled by pre-existing structures that produces anomalous volcanism at barriers to rift propagation and distributes continental material in the growing oceans fits other oceanic regions including the Davis Strait and the South Atlantic and West Indian oceans

    A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

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    Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

    Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

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    BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation

    Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

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    Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research
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