AGNs in massive galaxy clusters: Role of galaxy merging, infalling groups, cluster mass, and dynamical state

There is compelling evidence that active galactic nuclei (AGNs) in high-density regions have undergone a different evolution than their counterparts in the field, indicating that they are strongly affected by their environment. To investigate the various factors that may affect the prevalence of AGNs in cluster galaxies, we selected a sample of 19 thoroughly studied X-ray-selected galaxy clusters from the LoCuSS survey. All these clusters are considered massive, with $M_{500}\gtrsim 2\times10^{14} M_{solar}$, and span a narrow redshift range between $z\sim$0.16 and 0.28. We divided the cluster surroundings into two concentric annuli with a width of $R_{500}$ radius. We further divided the cluster sample based on the presence of infalling X-ray-detected groups, cluster mass, or dynamical state. We found that the X-ray AGN fraction in the outskirts is consistent with the field, but it is significantly lower in cluster centres, in agreement with previous results for massive clusters. We show that these results do not depend on cluster mass. Furthermore, we did not find any evidence of a spatial correlation between infalling groups and AGNs. Nevertheless, a significant excess of X-ray AGNs is found in the outskirts of relaxed clusters at the 2$\sigma$ confidence level, compared both to non-relaxed clusters and to the field. Our results suggest that the mechanisms that trigger AGN activity may vary between cluster centres and the outskirts. Ram pressure can efficiently remove the gas from infalling galaxies, thereby triggering AGN activity in some cases. However, the reduced availability of gas globally diminishes the fraction of AGNs in cluster centers. The surplus of X-ray AGNs identified in the outskirts of relaxed clusters may be attributed to an increased frequency of galaxy mergers, a notion that is further supported by the disturbed morphology observed in several galaxies.Comment: 14 pages, accepted in A&

Maintaining Clinical Freedom Whilst Achieving Value in Biologics Prescribing: An Integrated Cross-Specialty Consensus of UK Dermatologists, Rheumatologists and Gastroenterologists.

BACKGROUND: Biologics are now key drugs in the management of immune-mediated inflammatory diseases. However, the increasingly complex biologics environment and growing cost pressures in the UK have led to variability in drug commissioning and inequity of patient access across regions. OBJECTIVES: Our objectives were to provide consensus recommendations for enhancing the current situation in biologic prescribing in the UK by balancing clinical freedom with equitable distribution of biologics given the limited availability of resources. METHODS: A modified Delphi approach was used to reach integrated, cross-specialty consensus among dermatologists, rheumatologists and gastroenterologists practising within the English National Health Service (NHS). RESULTS: We describe the concepts of clinical freedom and clinical judgement and demonstrate how, together with patient choice, they can be exercised in the context of biologic prescribing in the NHS. We highlight that in England, local variations occur that are at odds with National Institute for Health and Care Excellence (NICE) guidance; these variably limit the degree to which clinicians can exercise clinical freedom and impact on equity of patient access to treatments. We define factors encompassing a drug's value and identify challenges to the measurement and interpretation of this concept, which can raise barriers to the freedom of clinical choice and appropriate prescribing decisions allowing practices of holistic and personalised medicine. Cross-specialty consensus recommendations on ensuring equitable access to biologics in the NHS while protecting appropriate and individualised drug selection for patients are provided. We have also provided strategies for improving physician-commissioner communication to harmonise equity of patient access to biologics across England and improve patient outcomes. Commentary from patient advisory groups indicates that they welcome our exploration that value does not equal cost and agree that there should be an emphasis on shared decision making, which requires the clinician to practice clinical freedom by aligning the patient's needs and preferences with available treatment choices. CONCLUSIONS: This consensus highlights the need to strike a balance between clinical freedom and short-term cost restrictions to support equitable resource distribution within the English NHS. Consideration of these recommendations may help to harmonise local, regional and national services and balance equity of patient access to biologic treatments with excellence in the NHS

WILL (When to Induce Labour to Limit risk in pregnancy hypertension): a multicentre randomised controlled trial - adaptations to deliver a timing-of-birth trial during the COVID-19 international pandemic.

BACKGROUND: As a pragmatic randomised timing-of-birth trial, WILL adapted its trial procedures in response to the COVID-19 pandemic. These are reviewed here to inform post-pandemic trial methodology. METHODS: The trial (internal pilot) paused in March 2020, re-opened in July 2020, and is currently recruiting in 37 UK NHS consultant-led maternity units. We evaluated pandemic adaptations made to WILL processes and surveyed sites for their views of these changes (20 sites, videoconference). RESULTS: Despite 88% of sites favouring an electronic investigator site file (ISF), information technology requirements and clinical trial unit (CTU) operating procedures mandated the ongoing use of paper ISFs; site start-up delays resulted from restricted access to the CTU. Site initiation visits (SIVs) were conducted remotely; 50% of sites preferred remote SIVs and 44% felt that it was trial-dependent, while few preferred SIVs in-person as standard procedure. The Central team felt remote SIVs provided scheduling and attendance flexibility (for sites and trial staff), the option of recording discussions for missing or future staff, improved efficiency by having multiple sites attend, and time and cost savings; the negative impact on rapport-building and interaction was partially mitigated over time with more familiarity with technology and new ways-of-working. Two methods of remote consent were developed and used by 30/37 sites and for 54/156 recruits. Most (86%) sites using remote consenting felt it improved recruitment. For remote data monitoring (5 sites), advantages were primarily for the monitor (e.g. flexibility, no time constraints, reduced cost), and disadvantages primarily for the sites (e.g. document and access preparation, attendance at a follow-up meeting), but 81% of sites desired having the option of remote monitoring post-pandemic. CONCLUSIONS: COVID adaptations to WILL trial processes improved the flexibility of trial delivery, for Central and site staff, and participants. Flexibility to use these strategies should be retained post-pandemic. TRIAL REGISTRATION: ISRCTN77258279. Registered on 05 December 2018

SN 2020zbf: A fast-rising hydrogen-poor superluminous supernova with strong carbon lines

SN 2020zbf is a hydrogen-poor superluminous supernova at $z = 0.1947$ that shows conspicuous C II features at early times, in contrast to the majority of H-poor SLSNe. Its peak magnitude is $M_{\rm g}$ = $-21.2$ mag and its rise time ($\lesssim 24$ days from first light) place SN 2020zbf among the fastest rising SLSNe-I. Spectra taken from ultraviolet (UV) to near-infrared wavelengths are used for the identification of spectral features. We pay particular attention to the C II lines as they present distinctive characteristics when compared to other events. We also analyze UV and optical photometric data, and model the light curves considering three different powering mechanisms: radioactive decay of Ni, magnetar spin-down and circumstellar material interaction (CSM). The spectra of SN 2020zbf match well with the model spectra of a C-rich low-mass magnetar model. This is consistent with our light curve modelling which supports a magnetar-powered explosion with a $M_{\rm ej}$ = 1.5 $M_\odot$. However, we cannot discard the CSM-interaction model as it also may reproduce the observed features. The interaction with H-poor, carbon-oxygen CSM near peak could explain the presence of C II emission lines. A short plateau in the light curve, around 30 - 40 days after peak, in combination with the presence of an emission line at 6580 \r{A} can also be interpreted as late interaction with an extended H-rich CSM. Both the magnetar and CSM interaction models of SN 2020zbf indicate that the progenitor mass at the time of explosion is between 2 - 5 $M_\odot$. Modelling the spectral energy distribution of the host reveals a host mass of 10$^{8.7}$ $M_\odot$, a star-formation rate of 0.24$^{+0.41}_{-0.12}$ $M_\odot$ yr$^{-1}$ and a metallicity of $\sim$ 0.4 $Z_\odot$.Comment: 26 pages, 22 figures, submitted to A&

An individual randomised efficacy trial of autologous blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in leprosy in Nepal : the TABLE trial protocol

Background: Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing. Methods: This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation. Discussion: This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers. Trial registration: ClinicalTrials.govISRCTN14933421. Registered on 16 June 202

Cumulative incidence and risk factors for cutaneous squamous-cell carcinoma metastases in organ transplant recipients: the SCOPE-ITSCC metastases study, a prospective multi-center study.

Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous-cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. Of 514 SOTRs who presented with 623 primary cSCCs, 37 developed metastases with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size >2cm, clinical ulceration, poor differentiation grade, perineural invasion and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9% - 68.4%). SOTRs have a high risk of cSCC metastases and well-established clinical and histological risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Spectroscopic observations of progenitor activity 100 days before a Type Ibn supernova ⋆

Obtaining spectroscopic observations of the progenitors of core-collapse supernovae is often unfeasible, due to an inherent lack of knowledge as to what stars experience supernovae and when they will explode. In this Letter we present photometric and spectroscopic observations of the progenitor activity of SN 2023fyq before the He-rich progenitor explodes as a Type Ibn supernova. The progenitor of SN 2023fyq shows an exponential rise in flux prior to core collapse. Complex He i emission line features are observed in the progenitor spectra, with a P Cygni-like profile, as well as an evolving broad base with velocities of the order of 10 000 km s-1. The luminosity and evolution of SN 2023fyq is consistent with a Type Ibn, reaching a peak r-band magnitude of-18:8 mag, although there is some uncertainty regarding the distance to the host, NGC 4388, which is located in the Virgo cluster. We present additional evidence of asymmetric He-rich material being present both prior to and after the explosion of SN 2023fyq, which suggests that this material survived the ejecta interaction. Broad [O i], C i, and the Ca ii triplet lines are observed at late phases, confirming that SN 2023fyq was a genuine supernova, rather than a non-Terminal interacting transient. SN 2023fyq provides insight into the final moments of a massive star's life, demonstrating that the progenitor is likely highly unstable before core collapse

Metabolism of 2-acylglycerol in rabbit and human platelets. Involvement of monoacylglycerol lipase and fatty acid amide hydrolase

The endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA) are produced by neurons and other cells, including platelets, in a stimulus-dependent manner and act as signaling molecules; they are then inactivated through transport into cells followed by enzymatic degradation. A number of studies showed that monoacylglycerol lipase (MAGL) plays an important role in the degradation of 2-AG. In this study we investigated the enzymatic degradation of 2-acylglycerols in rabbit platelets and we characterized the responsible enzyme(s). [ 3H]2-AG and [ 3H]2-oleoylglycerol (2-OG) were both metabolized to [ 3H]glycerol and the respective fatty acid in a time and protein concentration-dependent manner, apparently by the action of MAGL activity. In the presence of the specific fatty acid amide hydrolase (FAAH) inhibitors URB597 and AM374, though, 2-OG hydrolysis was inhibited up to 55% in a concentration-dependent manner (Ic50 = 129.8 nM and 20.9 nM respectively). These results indicate the involvement of both MAGL and FAAH on 2-acylglycerol hydrolysis. MAGL was further characterized in the presence of URB597 and it was found that 2-monoacylglycerols were hydrolyzed in a time, pH and protein concentration-dependent manner and hydrolysis followed Michaelis-Menten kinetics, with an apparent KM of 0.11 μM and Vmax of 1.32 nmol/min*mg protein. Subcellular fractionation of platelet homogenate showed that MAGL activity was present in both the cytosolic and membrane fractions. In conclusion, the endocannabinoid 2-AG, as well as other 2-acylglycerols, are substrates of both FAAH and MAGL; the latter was characterized for the first time in platelets. In human platelets, under the same experimental conditions, the hydrolysis of 2-acylglycerols was higher and MAGL activity showed a different sensitivity against the inhibitors mentioned above. Finally, immunoblot analysis revealed the presence of MAGL, both in rabbit and human platelets, with a molecular mass of ∼ü33 kDa. © 2009 Informa UK Ltd All rights reserved