A Markov Chain Monte Carlo approach for measurement of jet precession in radio-loud active galactic nuclei

© 2020 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Jet precession can reveal the presence of binary systems of supermassive black holes. The ability to accurately measure the parameters of jet precession from radio-loud AGN is important for constraining the binary supermassive black hole population, which are expected as a result of hierarchical galaxy evolution. The age, morphology, and orientation along the line of sight of a given source often result in uncertainties regarding jet path. This paper presents a new approach for efficient determination of precession parameters using a 2D MCMC curve-fitting algorithm which provides us a full posterior probability distribution on the fitted parameters. Applying the method to Cygnus A, we find evidence for previous suggestions that the source is precessing. Interpreted in the context of binary black holes leads to a constraint of parsec scale and likely sub-parsec orbital separation for the putative supermassive binary.Peer reviewe

3D Hydrodynamic Simulations of Large-Scale Precessing Jets : Radio Morphology

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society] ©: 2020 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved. The final published version is available at: https://doi.org/10.1093/mnras/staa3020.The prospect of relativistic jets exhibiting complex morphologies as a consequence of geodetic precession has long been hypothesised. We have carried out a 3D hydrodynamics simulation study varying the precession cone angle, jet injection speed and number of turns per simulation time. Using proxies for the radio emission we project the sources with different inclinations to the line of sight to the observer. We find that a number of different precession combinations result in characteristic `X' shaped sources which are frequently observed in radio data, and some precessing jet morphologies may mimic the morphological signatures of restarting radio sources. We look at jets ranging in scale from tens to hundreds of kiloparsecs and develop tools for identifying known precession indicators of point symmetry, curvature and jet misalignment from the lobe axis and show that, based on our simulation sample of precessing and non-precessing jets, a radio source that displays any of these indicators has a 98% chance of being a precessing source.Peer reviewe

Efficacy, tolerability and safety of biologic therapy in rheumatoid disease: patient considerations

Rheumatoid arthritis (RA) is a systemic inflammatory disease in which chronic inflammation leads to joint destruction and extra-articular complications. Early and effective inhibition of inflammation is critical in order to prevent the progressive joint damage that occurs rapidly after onset of the disease. In the past, treatment for this purpose was limited to conventional disease-modifying antirheumatic drugs (DMARDs), which were often suboptimal. Within the last decade however, the development of biologic therapies, targeted against cytokines and cells involved in the inflammatory process, has revolutionized the management of RA. Disease remission is now an achievable goal in newly diagnosed patients. Since the advent of the first tumor necrosis factor-α inhibitor in 1999, other biologics have proved necessary as individuals respond to varying degrees with different therapies. Several are now available for the treatment of patients with RA that remains active despite DMARD treatment. This article reviews the evidence, over the last decade, of the efficacy and safety of biologic therapies used in this context, and the recent clinical data supporting the use of biologic therapy earlier in the disease process as first-line therapy

New mechanisms for forming multiple hotspots in radio jets

Hotspots of radio galaxies are regions of shock-driven particle acceleration. Multiple hotspots have long been identified as potential indicators of jet movement or precession. Two frequent explanations describe a secondary hotspot as either the location of a prior jet termination point, or a deflected backflow-driven shock: the so-called Dentist's Drill and Splatter Spot models. We created high-resolution simulations of precessing jets with a range of parameters. In addition to the existing mechanisms, our results show three additional mechanisms for multiple hotspot formation: (1) the splitting of a large terminal hotspots into passive and active components; (2) jet stream splitting resulting in two active hotspots; (3) dynamic multiple hotspot complexes that form as a result of jet termination in a turbulent cocoon, linked here to rapid precession. We show that these distinct types of multiple hotspots are difficult to differentiate in synthetic radio maps, particularly hotspot complexes which can easily be mistaken for the jet itself. We discuss the implication for hypothesised binary supermassive black hole systems where jet precession is a key component of the morphology, and show a selection of potential precession candidates found using the LOFAR Two-Metre Sky Survey Data Release 2 (LoTSS DR2).Comment: 14 pages, 10 figure

Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment to target strategy

Objective: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early rheumatoid arthritis (RA), achieved with treat-to-target management in clinical practice. Methods: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by disease activity score (DAS28-CRP<2.6). Twelve month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on ultrasound (US) of 26 joints (total PDA score=0 or ≤1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. Results: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Amongst patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42%, 44% and 40%, respectively; absent/minimal PDA was detected in 62%, 66% and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of osteoarthritis predicted absence of PDA and lower total baseline PDA predicted absent/minimal PDA. Conclusion: DAS28-CRP remission and absence of PDA were observed in almost half of patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target

A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA)

Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis, with significant impact on quality of life and functional status. Whilst biologic disease modifying anti-rheumatic drugs (bDMARD) such as tumour necrosis factor-inhibitor (TNFi) agents have revolutionised outcomes in RA, early diagnosis with immediate conventional therapy, titrated in a treat to target approach is also associated with high remission rates. The main aim of the VEDERA study (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) is to assess the depth of remission, sustainability of remission and immunological normalisation induced by very early TNFi with etanercept (ETN) or standard of care +/- delayed ETN. Methods/Design VEDERA is a pragmatic, phase IV single-centre open-label randomised superiority trial of 120 patients with early, treatment-naive RA. Patients will be randomised 1:1 to first-line ETN and methotrexate (MTX) or MTX with additional synthetic disease modifying anti-rheumatic drugs (sDMARDs) according to a treat to target (TT) protocol with further step up to ETN and MTX after 24 weeks if remission is not achieved. Participants will have regular disease activity assessments and imaging evaluation including musculoskeletal ultrasound and MRI. The main objective of this study is to assess the proportion of patients with early RA that achieve clinical remission at 48 weeks, following either treatment strategy. In addition, the participants are invited to take part in a cardio-vascular sub-study (Coronary Artery Disease in RA, CADERA), which aims to identify the incidence of cardiovascular abnormalities in early RA. Discussion The hypothesis underlining this study is that very early treatment with first-line ETN increases the proportion of patients with rheumatoid arthritis achieving clinical remission, in comparison to conventional therapy. Trial registration NCT02433184, 23/04/201

The Limits to Moral Erosion in Markets: Social Norms and the Replacement Excuse

This paper studies the impact of a key feature of competitive markets on moral behavior: the possibility that a competitor will step in and conclude the deal if a conscientious market actor forgoes a profitable business opportunity for ethical reasons. We study experimentally whether people employ the argument "if I don’t do it, someone else will" to justify taking a narrowly self-interested action. Our data reveal a clear pattern. Subjects do not employ the "replacement excuse" if a social norm exists that classifies the selfish action as immoral. But if no social norm exists, subjects are more inclined to take a selfish action in situations where another subject can otherwise take it. By demonstrating the importance of social norms of moral behavior for limiting the power of the replacement excuse, our paper informs the long-standing debate on the effect of markets on morals

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570