Dissecting Galaxies: Separating Star Formation, Shock Excitation and AGN Activity in the Central Region of NGC 613

The most rapidly evolving regions of galaxies often display complex optical spectra with emission lines excited by massive stars, shocks and accretion onto supermassive black holes. Standard calibrations (such as for the star formation rate) cannot be applied to such mixed spectra. In this paper we isolate the contributions of star formation, shock excitation and active galactic nucleus (AGN) activity to the emission line luminosities of individual spatially resolved regions across the central 3 $\times$ 3 kpc$^2$ region of the active barred spiral galaxy NGC$\sim$613. The star formation rate and AGN luminosity calculated from the decomposed emission line maps are in close agreement with independent estimates from data at other wavelengths. The star formation component traces the B-band stellar continuum emission, and the AGN component forms an ionization cone which is aligned with the nuclear radio jet. The optical line emission associated with shock excitation is cospatial with strong $H_2$ and [Fe II] emission and with regions of high ionized gas velocity dispersion ($\sigma > 100$ km s$^{-1}$). The shock component also traces the outer boundary of the AGN ionization cone and may therefore be produced by outflowing material interacting with the surrounding interstellar medium. Our decomposition method makes it possible to determine the properties of star formation, shock excitation and AGN activity from optical spectra, without contamination from other ionization mechanisms.Comment: 16 pages, 12 figures. Accepted for publication in MNRA

Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Web-based application for reducing methamphetamine use among Aboriginal and Torres Strait Islander People: Randomized waitlist controlled trial

Background: Digital interventions can help to overcome barriers to care, including stigma, geographical distance, and a lack of culturally appropriate treatment options. “We Can Do This” is a web-based app that was designed with input from cultural advisors and end users to support Aboriginal and Torres Strait Islander people seeking to stop or reduce their use of methamphetamine and increase psychosocial well-being. Objective: This study aimed to evaluate the effectiveness of the “We Can Do This” web-based app as a psychosocial treatment for Aboriginal and Torres Strait Islander people who use methamphetamine. Methods: The web app was evaluated using a randomized waitlist controlled parallel group trial. Participants were Aboriginal and Torres Strait Islander people aged 16 years or older who self-identified as having used methamphetamine at least weekly for the past 3 months. Participants were randomized on a 1:1 ratio to receive either access to the web-based app for 6 weeks or a waitlist control group. Both groups received access to a website with harm minimization information. The primary outcome was days of methamphetamine use in the past 4 weeks assessed at 1, 2, and 3 months post randomization. Secondary outcomes included severity of methamphetamine dependence (Severity of Dependence Scale [SDS]), psychological distress (Kessler 10 [K10]), help-seeking behavior, and days spent out of role due to methamphetamine use. Results: Participants (N=210) were randomized to receive either access to the web-based app (n=115) or the waitlist control condition (n=95). Follow-up was 63% at 1 month, 57% at 2 months, and 54% at 3 months. There were no significant group differences in days of methamphetamine use in the past 4 weeks at 1 the month (mean difference 0.2 days, 95% CI -1.5 to -2), 2 months (mean difference 0.6 days, 95% CI -1 to 2.4 days) or 3 months (mean difference 1.4 days, 95% CI -0.3 to 3.3 days) follow-up. There were no significant group differences in K10 scores, SDS scores, days out of role, or help-seeking at any of the 3 follow-up timepoints. There was poor adherence to the web-based app, only 20% of participants in the intervention group returned to the web-based app after their initial log-in. Participants cited personal issues and forgetting about the web-based app as the most common reasons for nonadherence. Conclusions: We found poor engagement with this web-based app. The web-based app had no significant effects on methamphetamine use or psychosocial well-being. Poor adherence and low follow-up hindered our ability to accurately evaluate the effectiveness of the web-based app. Future web-based apps for this population need to consider methods to increase participant engagement

Responses to the primary health care needs of Aboriginal and Torres Strait Islander women experiencing violence: A scoping review of policy and practice guidelines

Issue Addressed It is demonstrated that primary health care (PHC) providers are sought out by women who experience violence. Given the disproportionate burden of violence experienced by Aboriginal and Torres Strait Islander women, it is essential there is equitable access to appropriate PHC services. This review aimed to analyse whether Australian PHC policy accounts for the complex needs of Aboriginal and Torres Strait Islander women experiencing violence and the importance of PHC providers responding to violence in culturally safe ways. Methods Using the Arskey and O’Malley framework, an iterative scoping review determined the policies for analysis. The selected policies were analysed against concepts identified as key components in responding to the needs of Aboriginal and Torres Strait Islander women experiencing violence. The key components are Family Violence, Violence against Aboriginal and Torres Strait Islander Women, Social Determinants of Health, Cultural Safety, Holistic Health, Trauma, Patient Centred Care and Trauma‐and‐Violence‐Informed Care. Results Following a search of Australian government websites, seven policies were selected for analysis. Principally, no policy embedded or described best practice across all key components. Conclusion The review demonstrates the need for a specific National framework supporting Aboriginal and Torres Strait Islander women who seek support from PHC services, as well as further policy analysis and review. So what Aboriginal and Torres Strait Islander women disproportionately experience more severe violence, with complex impact, than other Australian women. PHC policy and practice frameworks must account for this, together with the intersection of contemporary manifestations of colonialism and historical and intergenerational traum

Two Secreted Proteoglycans, Activators of Urothelial Cell-Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression.

Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer

Reducing methamphetamine use in Aboriginal and Torres Strait Islander communities with the “We Can Do This” web app: Qualitative evaluation of acceptability and feasibility

Background: Preventing and treating methamphetamine-related harm in Aboriginal and Torres Strait Islander populations is a significant challenge for health care services. Digital health care may offer opportunities to support individuals and families in ways that complement existing methamphetamine treatment options. This study responds to a community-identified priority as Aboriginal Community Controlled Health Services identified methamphetamine use as a key concern and sought support to respond to the needs of people who use methamphetamine and their families. Objective: This paper reports on a process evaluation of the web application’s acceptability and feasibility when used by clients and clinicians in residential rehabilitation services and primary care. This study is part of a larger project entitled “Novel Interventions to address Methamphetamine use in Aboriginal and Torres Strait Islander Communities” (NIMAC), which seeks to develop culturally appropriate and strengths-based prevention and treatment interventions to reduce methamphetamine related harm. “We Can Do This” was a web application developed for Aboriginal and Torres Strait Islander people who are seeking to reduce or stop methamphetamine use. Methods: Clinicians and clients who had used the web application were recruited through Aboriginal Community Controlled Health Services and Aboriginal residential rehabilitation services in urban and regional Victoria and South Australia. Unidentified usage data was collected from all participants. After using the web application, those who indicated a willingness to be interviewed were contacted and interviewed by phone or in person and asked about the feasibility and acceptability of the web application. The framework method of analysis was used to structure and summarise the resulting qualitative data. Results: Interviews with 24 clients and 11 clinicians explored the acceptability and feasibility of the web application. Acceptability incorporated the following domains: affective attitude, burden, ethicality, cultural appropriateness, coherence, opportunity cost, perceived effectiveness, and self-efficacy. The evaluation of feasibility assessed barriers and facilitators to the implementation of the program, with a focus on demand, practicality, fidelity, and integration. Results indicated that both clients and clinicians found the web application content coherent, relatable, empowering, and culturally safe. Barriers to using the web application for clients included a lack of internet connectivity and personal issues such as scheduling. Conclusions: Process evaluation is often under-valued. However, as “We Can Do This” was new, innovative and targeted a hard-to-reach population, understanding its feasibility and acceptability as a clinical tool was essential to understanding its potential. “We Can Do This” is unique as the only evidence-based, culturally appropriate internet-based therapeutic program specifically designed for Aboriginal and Torres Strait Islander people who use methamphetamine. Findings suggest it was both acceptable and feasible as a low-cost adjunct to usual care in residential rehabilitation and primary care settings

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden