An investigation of the laser-induced zircon 'matrix effect'

This study aims to improve our understanding of the current limitations to high-precision U-Pb analysis of zircon by LA-ICP-MS by investigating the underlying causes of variation in ablation behaviour between different zircon matrices. Multiple factors such as: the degree of accumulated radiation damage, trace element composition; crystal colour; and crystallographic orientation are all systematically investigated. Due to the marked decrease in elastic moduli of natural zircon crystals with increasing radiation damage, the accumulation of this damage is the dominant factor controlling the rate of ablation for partially damaged to highly metamict zircon samples. There are slight differences, however, in ablation behaviour between highly crystalline matrices that cannot be attributed solely to differences in the degree of accumulated radiation damage. These differences are associated with structural weakening (i.e., decrease in elastic moduli and overall lower mechanical resistance) caused by an increasing degree of cation substitution in some of the zircon samples. Effects of crystallographic orientation and of crystal opacity (i.e., colour) on ablation behaviour are negligible compared to the combined influences of accumulated radiation damage and trace element substitution into the zircon structure. Experiments performed on natural and annealed zircon grains reveal that the reduction in ablation rates observed for the treated samples compared to the untreated grains is proportional to the degree of structural reconstitution achieved after annealing. Thermal annealing of natural zircon at temperatures >1000 °C results in much more uniform ablation characteristics. This 'homogenisation' of ablation behaviour between zircon matrices produces a decrease in the laser-induced matrix effects and subsequent improvement in the accuracy of 206Pb/238U ratio determinations by LA-ICP-MS

Population demographics of golden perch (Macquaria ambigua) in the Darling River prior to a major fish kill: A guide for rehabilitation

An understanding of population demographics and life history processes is integral to the rehabilitation of fish populations. In Australia's highly modified Murray-Darling Basin, native fish are imperilled and fish deaths in the Darling River in 2018-19 highlighted their vulnerability. Golden perch (Macquaria ambigua) is a long-lived percichthyid that was conspicuous in the fish kills. To guide population rehabilitation in the Darling River, pre-fish kill age structure, provenance and movement of golden perch were explored using otolith microstructure and chemistry (87Sr/86Sr). Across the Lower and Mid-Darling River, recruitment was episodic, with dominant cohorts associated with years characterised by elevated discharge. There was substantial variability in age structure, recruitment source and movement patterns between the Lower and Mid-Darling River. In the Mid-Darling River, tributaries were an important recruitment source, whereas in the Lower Darling fish predominantly originated in the Darling River itself. Downstream movement of juveniles, upstream migration of adults and return movements to natal locations were important drivers of population structure. Restoring resilient golden perch populations in the Darling River will be reliant on mitigating barriers to movement, promoting a connected mosaic of recruitment sources and reinstating the hydrological and hydraulic factors associated with spawning, recruitment and dispersal. Globally, increasing water resource development and climate change will necessitate such integrated approaches to the management of long-lived migratory riverine fishes. © 2022 Journal Compilatio

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

Efficient Visual Object and Word Recognition Relies on High Spatial Frequency Coding in the Left Posterior Fusiform Gyrus: Evidence from a Case-Series of Patients with Ventral Occipito-Temporal Cortex Damage

Seeing a face in motion can improve face recognition in the general population, and studies of face matching indicate that people with face recognition difficulties (developmental prosopagnosia; DP) may be able to use movement cues as a supplementary strategy to help them process faces. However, the use of facial movement cues in DP has not been examined in the context of familiar face recognition. This study examined whether people with DP were better at recognizing famous faces presented in motion, compared to static. Methods: Nine participants with DP and 14 age-matched controls completed a famous face recognition task. Each face was presented twice across 2 blocks: once in motion and once as a still image. Discriminability (A) was calculated for each block. Results: Participants with DP showed a significant movement advantage overall. This was driven by a movement advantage in the first block, but not in the second block. Participants with DP were significantly worse than controls at identifying faces from static images, but there was no difference between those with DP and controls for moving images. Conclusions: Seeing a familiar face in motion can improve face recognition in people with DP, at least in some circumstances. The mechanisms behind this effect are unclear, but these results suggest that some people with DP are able to learn and recognize patterns of facial motion, and movement can act as a useful cue when face recognition is impaired

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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

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

Pan-African intraplate deformation in the northern Prince Charles Mountains, east Antarctica

New structural and metamorphic data coupled with U-Pb SHRIMP zircon and Rb-Sr step-leach biotite ages help constrain a period of Early Palaeozoic (Pan-African) deformation recognised in the northern Prince Charles Mountains, east Antarctica. This period of deformation is accommodated along discrete northeast trending mylonites that preserve up-dip reverse kinematics with dominantly southeast over northwest vergence. Ambient P-T conditions of 524 ± 20°C and 7.6 ± 4 kbar accompanied deformation. This phase of deformation post-dated the intrusion of planar felsic dykes that yield ages of c. 550 Ma and pre-dated Rb-Sr biotite ages of c. 475 Ma that record cooling of the terrane below c. 300°C. These mylonites are identical in age to continental collisional events recognised in the southern Prince Charles Mountains and Prydz Bay, which lie to the south and east of the northern Prince Charles Mountains, and similar in age to orogenesis recognised to the west in Lützow-Holm Bay. These belts represent sutures between the component lithospheric blocks of east and west Gondwana. The northern Prince Charles Mountains lie between these sutures. Consequently, the mylonites we report here are interpreted to have formed in an intraplate setting and developed in response to stresses applied along the plated margins as a consequence of continental collision during the amalgamation of Gondwana

Temporal and spatial variation in strontium in a tropical river: implications for otolith chemistry analyses of fish migration

Analysis of otolith strontium isotope ratios 87Sr/86Sr is an increasingly utilised approach for studying fish migration. We analysed surface and groundwater from the Daly River catchment in the wet-dry tropics of Northern Australia over two years. Analyses of otolith 87Sr/86Sr ratios were also conducted for freshwater Sooty grunter (Hephaestus fuliginosus) and the putatively diadromous Ord River mullet (Liza ordensis). Spatial variation in freshwater 87Sr/86Sr was high (range: 0.71612-0.78059) and there was strong seasonality in water 87Sr/86Sr, with highest values in the wet season. Temporal variation in water 87Sr/86Sr ratios is attributed to seasonal patterns in surface run-off from geological formations with radiogenic compositions versus input from groundwater aquifers interacting with less radiogenic formations. Temporal variation in water 87Sr/86Sr ratios precluded robust inference on movement within freshwater for both species, although movement across salinity gradients by Ord River mullet was clearly identified. We conclude that temporally and spatially replicated water Sr data should be a general requisite for studies that analyse otolith Sr (87Sr/86Sr, Sr/Ca, Sr/Ba) to make inferences about fish movement and migration.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Australopithecus sediba at 1.977 Ma and implications for the origins of the genus Homo

Newly exposed cave sediments at the Malapa site include a flowstone layer capping the sedimentary unit containing the Australopithecus sediba fossils. Uranium-lead dating of the flowstone, combined with paleomagnetic and stratigraphic analysis of the flowstone and underlying sediments, provides a tightly constrained date of 1.977 ± 0.002 million years ago (Ma) for these fossils. This refined dating suggests that Au. sediba from Malapa predates the earliest uncontested evidence for Homo in Africa