Outcrop-scale manifestations of reactivation during multiple superimposed rifting and basin inversion events: the Devonian Orcadian Basin, northern Scotland

The Devonian Orcadian Basin in Scotland hosts extensional fault systems assumed to be related to the initial formation of the basin, with only limited post-Devonian inversion and reactivation. However, a recent detailed structural study across Caithness, underpinned by published Re–Os geochronology, shows that three phases of deformation are present. North–south- and NW–SE-trending Group 1 faults are related to Devonian ENE–WSW transtension associated with sinistral shear along the Great Glen Fault during the formation of the Orcadian Basin. Metre- to kilometre-scale north–south-trending Group 2 folds and thrusts are developed close to earlier sub-basin-bounding faults and reflect late Carboniferous–early Permian east–west inversion associated with dextral reactivation of the Great Glen Fault. The dominant Group 3 structures are dextral oblique NE–SW-trending and sinistral east–west-trending faults with widespread syndeformational carbonate mineralization (± pyrite and bitumen) and are dated using Re–Os geochronology as Permian (c. 267 Ma). Regional Permian NW–SE extension related to the development of the offshore West Orkney Basin was superimposed over pre-existing fault networks, leading to local oblique reactivation of Group 1 faults in complex localized zones of transtensional folding, faulting and inversion. The structural complexity in surface outcrops onshore therefore reflects both the local reactivation of pre-existing faults and the superimposition of obliquely oriented rifting episodes during basin development in the adjacent offshore areas

A revised age, structural model and origin for the North Pennine Orefield in the Alston Block, northern England: intrusion (Whin Sill)-related base metal (Cu–Pb–Zn–F) mineralization

Mineralization and associated fluid migration events in the c. 1500 km2 North Pennine Orefield (NPO) are known to be associated with tectonic activity, but the age of these tectonic events and origins of the base metal sulfide mineralization remain unresolved. New fieldwork in the Alston Block shows that mineralization post-dates a weakly developed phase of north–south shortening consistent with far-field Variscan basin inversion during the late Carboniferous. New observations of field relationships, coupled with microstructural observations and stress inversion analyses, together with Re–Os sulfide geochronology show that the vein-hosted mineralization (apart from barium minerals) was synchronous with a phase of north–south extension and east–west shortening coeval with emplacement of the Whin Sill (c. 297–294 Ma). Thus the development of the NPO was related to an early Permian regional phase of transtensional deformation, mantle-sourced hydrothermal mineralization and magmatism in northern Britain. Previously proposed Mississippi Valley Type models, or alternatives relating mineralization to the influx of Mesozoic brines, can no longer be applied to the development of the NPO in the Alston Block. Our findings also mean that existing models for equivalent base metal sulfide fields worldwide (e.g. Zn–Pb districts of Silesia, Poland and Tennessee, USA) may need to be reassessed

The Neoarchaean Uyea Gneiss Complex, Shetland: an onshore fragment of the Rae Craton on the European Plate

A tract of amphibolite facies granitic gneisses and metagabbros in northern Shetland, U.K., is here named the Uyea Gneiss Complex. Zircon U–Pb dating indicates emplacement of the igneous protoliths of the complex c. 2746–2726 Ma, at a later time than most of the Archaean protoliths of the Lewisian Gneiss Complex of mainland Scotland. Calc-alkaline geochemistry of the Uyea Gneiss Complex indicates arc-affinity and a strong genetic kinship among the mafic and felsic components. Zircon Hf compositions suggest an enriched mantle source and limited interaction with older crust during emplacement. Ductile fabrics developed soon after emplacement, with zircon rims at c. 2710 Ma, but there was little further deformation until Caledonian reworking east of the Uyea Shear Zone. There is no evidence for the Palaeoproterozoic reworking that dominates large tracts of the Lewisian Gneiss Complex and of the Nagssugtoqidian Orogen of East Greenland. The more northerly location of the Uyea Gneiss Complex and extensive offshore basement of similar age implies that, prior to the opening of the North Atlantic Ocean, these rocks were contiguous with the Archaean Rae Craton

The Effects of Disorder on the ν=1\nu=1 Quantum Hall State

A disorder-averaged Hartree-Fock treatment is used to compute the density of single particle states for quantum Hall systems at filling factor $\nu=1$. It is found that transport and spin polarization experiments can be simultaneously explained by a model of mostly short-range effective disorder. The slope of the transport gap (due to quasiparticles) in parallel field emerges as a result of the interplay between disorder-induced broadening and exchange, and has implications for skyrmion localization.Comment: 4 pages, 3 eps figure

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

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

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease