Assessing Inequalities in Wellbeing at a Neighbourhood Scale in Low-Middle-Income-Country Secondary Cities and Their Implications for Long-Term Livability

Correction: FEB 15 2022 DOI10.3389/fsoc.2022.856609To ensure future sustainability, cities need to consider concepts of livability and resident wellbeing alongside environmental, economic and infrastructure development equity. The current rapid urbanization experienced in many regions is leading to sustainability challenges, but also offers the opportunity to deliver infrastructure supporting the social aspects of cities and the services that underpin them alongside economic growth. Unfortunately, evidence of what is needed to deliver urban wellbeing is largely absent from the global south. This paper contributes to filling this knowledge gap through a novel interdisciplinary mixed methods study undertaken in two rapidly changing cities (one Thai and one Kenyan) using qualitative surveys, subjective wellbeing and stress measurements, and spatial analysis of urban infrastructure distribution. We find the absence of basic infrastructure (including waste removal, water availability and quality) unsurprisingly causes significant stress for city residents. However, once these services are in place, smaller variations (inequalities) in social (crime, tenure) and environmental (noise, air quality) conditions begin to play a greater role in determining differences in subjective wellbeing across a city. Our results indicate that spending time in urban greenspaces can mitigate the stressful impacts of city living even for residents of informal neighborhoods. Our data also highlights the importance of places that enable social interactions supporting wellbeing-whether green or built. These results demonstrate the need for diversity and equity in the provision of public realm spaces to ensure social and spatial justice. These findings strengthen the need to promote long term livability in LMIC urban planning alongside economic growth, environmental sustainability, and resilience.Peer reviewe

Spectacles of intimacy? Mapping the moral landscape of teenage social media

This paper explores young people's expressed concerns about privacy in the context of a highly mediated cultural environment, mapping social media practices against axes of visibility and participation. Drawing on interdisciplinary conceptual resources from both the humanities and social sciences, we use ‘spectacles of intimacy’ to conceptualise breaches of privacy, mapping an emergent moral landscape for young people that moves beyond concerns with e-safety to engage with the production and circulation of audiences and value. The paper draws on data from a methodological innovation project using multi-media and mixed methods to capture lived temporalities for children and young people. We present a model that captures a moral landscape shaped by emotional concerns about social media, the affordances of those media and affective discourses emerging from young people's use of the media

Legitimacy in the Multilevel European Polity

In order to be simultaneously effective and liberal, governments must normally be able to count on voluntary compliance – which, in turn, depends on the support of socially shared legitimacy beliefs. In Western constitutional democracies, such beliefs are derived from the distinct but coexistent traditions of “republican” and “liberal” political philosophy. When judged by these criteria, the European Union – if considered by itself – appears as a thoroughly liberal polity which, however, lacks all republican credentials. But this view (which seems to structure the debates about the “European democratic deficit”) ignores the multilevel nature of the European polity, where the compliance of citizens is requested, and needs to be legitimated by member states – whereas the Union appears as a “government of governments” which is entirely dependent on the voluntary compliance of its member states. What matters primarily, therefore, is the compliance-legitimacy relationship between the Union and its member states – which, however, is normatively constrained by the basic compliance-legitimacy relationship between member governments and their constituents. Given the high consensus requirements of European legislation, member governments could and should be able to assume political responsibility for European policies in which they had a voice, and to justify them in “communicative discourses” in the national public space. This is not necessarily true of “non-political” policy choices imposed by the European Court of Justice. By enforcing its “liberal” program of liberalization and deregulation, the ECJ may presently be undermining the “republican” bases of member-state legitimacy. Where this is the case, open non-compliance is a present danger, and political controls of judicial legislation may be called for.Um gleichzeitig effektiv und liberal sein zu können, ist staatliche Herrschaft auf freiwillige Folgebereitschaft angewiesen – die ihrerseits der Unterstützung durch sozial geteilte Legitimitätsüberzeugungen bedarf. In den demokratischen Verfassungsstaaten des Westens werden solche Überzeugungen aus den unterschiedlichen, aber komplementär zusammenwirkenden Traditionen der „republikanischen“ und der „liberalen“ politischen Philosophie hergeleitet. An diesen Kriterien gemessen erscheint die Europäische Union – wenn man sie für sich betrachtet – als eine „liberale“ politische Ordnung, der jedoch alle „republikanischen“ Legitimitätsmerkmale fehlen. Aber eine solche Sichtweise, die auch die derzeitige Diskussion über ein „europäisches Demokratiedefizit“ bestimmt, verkennt den Mehrebenencharakter des europäischen Gemeinwesens. In ihm sind es die Mitgliedstaaten, die Entscheidungen der Union gegenüber den eigenen Bürgern durchsetzen und auch legitimieren müssen, während es für die Union ihrerseits auf die freiwillige Folgebereitschaft ihrer Mitgliedstaaten ankommt. Dabei werden diese jedoch durch die normativen Grundlagen ihrer eigenen Legitimität begrenzt. Politische Entscheidungen auf europäischer Ebene setzen breiten Konsens voraus, und die Regierungen sollten sie deshalb auch gegenüber den eigenen Bürgern in „kommunikativen Diskursen“ vertreten und dafür die politische Verantwortung übernehmen können. Dies gilt jedoch nicht notwendigerweise auch für Entscheidungen der europäischen Politik, die im nichtpolitischen Modus ohne Beteiligung des Rates und des Parlaments vom Europäischen Gerichtshof bestimmt werden. Mit der gegenwärtigen Radikalisierung seines „liberalen“ Programms der Liberalisierung und Deregulierung des nationalen Rechts könnte der Gerichtshof in der Tat die „republikanischen“ Grundlagen der mitgliedstaatlichen Legitimität unterminieren. In diesem Falle könnte die Union sich nicht länger auf die Folgebereitschaft ihrer Mitgliedstaaten verlassen. Um diese Gefahr für die europäische Integration zu vermeiden, sollte eine stärkere politische Kontrolle der richterlichen Rechtsetzung erwogen werden.1 Legitimacy Republican and liberal legitimating discourses Constitutional democracies – and the EU? 2 Legitimacy in multilevel polities 3 Legitimating member state compliance Political modes of policy making Non-political policy making 4 The need for justification 5 The Court is pushing against the limits of justifiability 6 The liberal undermining of republican legitimacy 7 Needed: A political balance of community and autonomy Reference

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Temperature-dependent alterations in host use drive rapid range expansion in a butterfly

Responses of species to climate change are extremely variable, perhaps because of climate-related changes to interactions among species. We show that temperature-related changes in the dependence of the butterfly Aricia agestis on different larval host plants have facilitated rapid range expansion. Historically, the butterfly was largely restricted to a single plant species, Helianthemum nummularium, but recent warmer conditions have enabled the butterfly to increasingly use the more widespread plant species Geranium molle. This has resulted in a substantial increase in available habitat and rapid range expansion by the butterfly (79 kilometers northward in Britain in 20 years). Interactions among species are often seen as constraints on species’ responses to climate change, but we show that temperature-dependent changes to interspecific interactions can also facilitate change