The Incidence of X-ray selected AGN in Nearby Galaxies

We present the identification and analysis of an unbiased sample of AGN that lie within the local galaxy population. Using the MPA-JHU catalogue (based on SDSS DR8) and 3XMM DR7 we define a parent sample of 25,949 local galaxies ($z \leq 0.33$). After confirming that there was strictly no AGN light contaminating stellar mass and star-formation rate calculations, we identified 917 galaxies with central, excess X-ray emission likely originating from an AGN. We analysed their optical emission lines using the BPT diagnostic and confirmed that such techniques are more effective at reliably identifying sources as AGN in higher mass galaxies: rising from 30% agreement in the lowest mass bin to 93% in the highest. We then calculated the growth rates of the black holes powering these AGN in terms of their specific accretion rates ($\propto L_X/M_*$). Our sample exhibits a wide range of accretion rates, with the majority accreting at rates $\leq 0.5\%$ of their Eddington luminosity. Finally, we used our sample to calculate the incidence of AGN as a function of stellar mass and redshift. After correcting for the varying sensitivity of 3XMM, we split the galaxy sample by stellar mass and redshift and investigated the AGN fraction as a function of X-ray luminosity and specific black hole accretion rate. From this we found the fraction of galaxies hosting AGN above a fixed specific accretion rate limit of $10^{-3.5}$ is constant (at $\approx 1\%$) over stellar masses of $8 < \log \mathrm{M_*/M_\odot} < 12$ and increases (from $\approx 1\%$ to $10\%$) with redshift.Comment: 18 pages, 10 figures, 2 appendices. Accepted for publication in MNRA

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. Funding Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

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&lt;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&lt;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&lt;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 &gt;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

Characterising the X-ray selected AGN Content of the Nearby Universe

Large-scale surveys of the Active Galactic Nuclei (AGN) population performed over the past few decades have highlighted the existence of strong correlations between the central supermassive black hole and their host galaxy. Whilst such samples are incredibly useful, they tend to be incomplete. This skews our understanding of the AGN population as samples consist of largely brighter, more actively accreting objects. In this thesis, I combined SDSS galaxy samples with XMM-Newton serendipitous sources to measure the incidence of AGN as a function of galaxy properties in the nearby (z < 0:35) Universe, carefully accounting for the incompleteness of the X-ray imaging. Regardless of how the galaxy population were split, the probability of hosting an AGN was well described by a power law and highlighted significant amounts of activity at low X-ray luminosities and accretion rates. I identified 61 AGN in dwarf galaxies, of which 40 have not been previously identified. The probability of hosting an AGN in this regime was unaffected by either the stellar mass or redshift of the host galaxy. Then I studied the wider local galaxy population. As with dwarf galaxies, the probability of hosting an AGN is not affected by stellar mass but it does increases with redshift. When comparing my results to higher redshift measurements, I identified a stellar-mass-dependent distribution of black hole growth rates. Finally, I investigated the effect of star-forming activity. I found that the probability of a galaxy hosting an AGN increases with the star formation rate. Throughout, I also compared the effectiveness of AGN selection at X-ray and optical wavelengths. I found that the BPT diagnostic is not as effective as X-ray selection. The optical diagnostic incorrectly classified a significant proportion of the X-ray selected AGN sample as star-forming, and was unable to identify weak AGN emission.</div

The incidence of X-ray selected AGN in nearby galaxies

We present the identification and analysis of an unbiased sample of active galactic nuclei (AGN) that lie within the local galaxy population. Using the MPA-JHU catalogue (based on SDSS DR8) and 3XMM DR7 we define a parent sample of 25 949 local galaxies (z ≤ 0.33). After confirming that there was strictly no AGN light contaminating stellar mass and star-formation rate calculations, we identified 917 galaxies with central, excess X-ray emission likely originating from an AGN. We analysed their optical emission lines using the BPT diagnostic and confirmed that such techniques are more effective at reliably identifying sources as AGN in higher mass galaxies: rising from 30 per cent agreement in the lowest mass bin to 93 per cent in the highest. We then calculated the growth rates of the black holes powering these AGN in terms of their specific accretion rates (∝LX/M*). Our sample exhibits a wide range of accretion rates, with the majority accreting at rates ≤0.5 percent of their Eddington luminosity. Finally, we used our sample to calculate the incidence of AGN as a function of stellar mass and redshift. After correcting for the varying sensitivity of 3XMM, we split the galaxy sample by stellar mass and redshift and investigated the AGN fraction as a function of X-ray luminosity and specific black hole accretion rate. From this we found the fraction of galaxies hosting AGN above a fixed specific accretion rate limit of 10−3.5 is constant (at ≈1 percent⁠) over stellar masses of 8 < log M*/M⊙ < 12 and increases (from ≈1 percent to 10 per cent) with redshift.</p

XMM2ATHENA, the H2020 project to improve XMM-Newton analysis software and prepare for Athena

XMM-Newton, a European Space Agency observatory, has been observing the X-ray, ultra-violet, and optical sky for 23 years. During this time, astronomy has evolved from mainly studying single sources to populations and from a single wavelength, to multi-wavelength/messenger data. We are also moving into an era of time domain astronomy. New software and methods are required to accompany evolving astronomy and prepare for the next-generation X-ray observatory, Athena. Here we present XMM2ATHENA, a program funded by the European Union's Horizon 2020 research and innovation program. XMM2ATHENA builds on foundations laid by the XMM-Newton Survey Science Centre (XMM-SSC), including key members of this consortium and the Athena Science ground segment, along with members of the X-ray community. The project is developing and testing new methods and software to allow the community to follow the X-ray transient sky in quasi-real time, identify multi-wavelength/messenger counterparts of XMM-Newton sources and determine their nature using machine learning. We detail here the first milestone delivery of the project, a new online, sensitivity estimator. We also outline other products, including the forthcoming innovative stacking procedure and detection algorithms, to detect the faintest sources. These tools will then be adapted for Athena and the newly detected/identified sources will enhance preparation for observing the Athena X-ray sky

XMM2ATHENA, the H2020 project to improve XMM-Newton analysis software and prepare for Athena

International audienceXMM-Newton, a European Space Agency observatory, has been observing the X-ray, ultra-violet and optical sky for 23 years. During this time, astronomy has evolved from mainly studying single sources to populations and from a single wavelength, to multi-wavelength or messenger data. We are also moving into an era of time domain astronomy. New software and methods are required to accompany evolving astronomy and prepare for the next generation X-ray observatory, Athena. Here we present XMM2ATHENA, a programme funded by the European Union's Horizon 2020 research and innovation programme. XMM2ATHENA builds on foundations laid by the XMM-Newton Survey Science Centre (XMM-SSC), including key members of this consortium and the Athena Science ground segment, along with members of the X-ray community. The project is developing and testing new methods and software to allow the community to follow the X-ray transient sky in quasi-real time, identify multi-wavelength or messenger counterparts of XMM-Newton sources and determine their nature using machine learning. We detail here the first milestone delivery of the project, a new online, sensitivity estimator. We also outline other products, including the forthcoming innovative stacking procedure and detection algorithms to detect the faintest sources. These tools will then be adapted for Athena and the newly detected or identified sources will enhance preparation for observing the Athena X-ray sky