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SummaryAllergic asthma generally starts during early life and is linked to significant tissue remodelling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLS), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MCs) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-Cadherin. Furthermore, spatial transcriptomics of paediatric asthmatic endobronchial biopsies revealed intense remodelling associated with increased expression of MC proteases in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.

The paper presents a simple directed cellular automata model for the R environment, applied to model the spatial diffusion of a hypothetical past hominin population. At the model start time, an agent (individual or group) occupies a cell, and scans the cell neighbourhood for the most suitable next step. A cost function is implemented whereby the agent will choose the minimum slope within the neighbourhood at each step, but this could be any other suitability surface that might influence an agent's movement decisions, i.e water, game, vegetation etc. The model could be applied at any spatial or temporal scale, from migrations out of an occupation site over a number of days, to an ocean voyage measured in weeks or months, to a species dispersion event measured in millennia. The model could also be applied to practically any dispersion case for which data are available, e.g. viruses, vegetation or airborne particles. Full R script code and data required to run the model are provided as supplementary material.

Aberrant expansion of KRT5+basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5+cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5+cells migrate within the fibrotic lung, navigating regional differences in collagen topography.In vitro, KRT5+cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry-based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5+cell migrationin vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5+cell behaviour and function contributing to remodelling events in the fibrotic niche.

Interstitial lung abnormalities (ILA) can be incidentally detected in patients undergoing low-dose CT screening for lung cancer. In this retrospective study, we explore the downstream impact of ILA detection on interstitial lung disease (ILD) diagnosis and treatment. Using a targeted approach in a lung cancer screening programme, the rate of de novo ILD diagnosis was 1.5%. The extent of abnormality on CT and severity of lung function impairment, but not symptoms were the most important factors in differentiating ILA from ILD. Disease modifying therapies were commenced in 39% of ILD cases, the majority being antifibrotic therapy for idiopathic pulmonary fibrosis.

The community of cells lining our airways plays a collaborative role in the preservation of immune homeostasis in the lung and provides protection from the pathogens and pollutants in the air we breathe. In addition to its structural attributes that provide effective mucociliary clearance of the lower airspace, the airway epithelium is an immunologically active barrier surface that senses changes in the airway environment and interacts with resident and recruited immune cells. Single-cell RNA-sequencing is illuminating the cellular heterogeneity that exists in the airway wall and has identified novel cell populations with unique molecular signatures, trajectories of differentiation and diverse functions in health and disease. In this Review, we discuss how our view of the airway epithelial landscape has evolved with the advent of transcriptomic approaches to cellular phenotyping, with a focus on epithelial interactions with the local neuronal and immune systems., In this Review, Lloyd and Hewitt describe our contemporary understanding of the airway epithelial cell landscape. They highlight the new epithelial cell types that have been recently discovered and explain how epithelial cells interact with the immune and nervous systems to shape immunity in the airways.

Landscapes are changing, with rural areas becoming increasingly urbanized. Children and adolescents are underrepresented in the sense-of-place literature. Our study aimed to understand how adolescent residents of a rural–urban transition area perceive and value their urbanizing landscape by examining sense of place and perceptions of landscape change. A Public Participation GIS approach, accompanied by a questionnaire survey, was applied to elicit responses from a sample of 747 students aged 12–18 in Colmenar Viejo, Madrid (Spain). Respondents’ sense of “self-in-place” or home range was small, around 1 km, although valued places were identified up to around 17 km away, and occasionally further afield. Most responses were associated with urban land, with clear difference between the urban core, strongly associated with emotions, and the suburbs, with activities. Functional locations (i.e. sports facilities) and places which were valued for their social meaning (i.e. shopping malls), could be differentiated. Students were perceptive about change processes in the urban area, but not about those on the peripheral semi-natural land. Younger children were less aware than older children of spaces outside of the town and carried out fewer activities there. Females carried out fewer outdoor activities than male adolescents. In contrast to the adult population, students were more strongly focused on urban areas than on their surrounding rural landscapes. Here, awareness-raising and incentives are needed, particularly those encouraging females into the use of areas beyond the urban land. Our results suggest a lack of meaningful integration between the core city and the periphery, with lessons for urban planners.

Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airway and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. 1 year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells., Graphical Abstract, Many individuals recovering from acute SARS-CoV-2 infection suffer prolonged respiratory dysfunction for months to years after viral clearance. Vijayakumar, Boustani, Ogger, Papadaki et al. show that individuals with persistent symptoms 3-6 months after infection have an altered airway immune cell landscape and evidence of ongoing lung damage. Importantly, different immune cell types correlate with the severity of distinct aspects of ongoing respiratory disease.

Children are less likely than adults to suffer severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while influenza A H1N1 severity is comparable across ages except for the very young or elderly. Airway epithelial cells play a vital role in the early defence against viruses via their barrier and immune functions. We investigated viral replication and immune responses in SARS-CoV-2-infected bronchial epithelial cells from healthy paediatric (n = 6; 2.5-5.6 years old) and adult (n = 4; 47-63 years old) subjects and compared cellular responses following infection with SARS-CoV-2 or Influenza A H1N1. While infection with either virus triggered robust transcriptional interferon responses, including induction of type I (IFNB1) and type III (IFNL1) interferons, markedly lower levels of interferons and inflammatory proteins (IL-6, IL-8) were released following SARS-CoV-2 compared to H1N1 infection. Only H1N1 infection caused disruption of the epithelial layer. Interestingly, H1N1 infection resulted in sustained upregulation of SARS-CoV-2 entry factors FURIN and NRP1. We did not find any differences in the epithelial response to SARS-CoV-2 infection between paediatric and adult cells. Overall, SARS-CoV-2 had diminished potential to replicate, affect morphology and evoke immune responses in bronchial epithelial cells compared to H1N1.

P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.

Coastal and terrestrial fisheries communities in Europe, often economically marginalised, are likely to face severe impacts as climate change becomes more acute. Although progress on climate mitigation and adaptation from national governments remains slow, local development actions can also address these impacts from the bottom up. In this paper we analyse the Fisheries and Sea Operational Programme 2014–2020 and 36 Local Development Strategies prepared within the framework of this programme for the case of Poland. The strategies, which were prepared by cross-sectoral, area-based partnerships known as Fisheries Local Action Groups, are analysed using a content analysis approach. The aim was to assess the degree to which local stakeholders sought to address the climate challenge. We found that the mitigation of climate impacts and the development of renewable energy did not feature prominently in the analysed documents, suggesting that both central policymakers and local stakeholders in Polish fisheries regions had a low level of awareness about the climate problem and their potentially important role in addressing it. Transformation to a post-carbon society undoubtedly requires additional, targeted support and extensive educational activities at the local level, in Poland and elsewhere.

SummarySome patients hospitalized with acute COVID19 suffer respiratory symptoms that persist for many months. To characterize the local and systemic immune responses associated with this form of ‘Long COVID’, we delineated the immune and proteomic landscape in the airway and peripheral blood of normal volunteers and patients from 3 to 6 months after hospital discharge. The bronchoalveolar lavage (but not peripheral blood) proteome was abnormal in patients with post-COVID19 lung disease with significantly elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury. This correlated with an increase in cytotoxic lymphocytes (especially tissue resident CD8+T cells), lactate dehydrogenase and albumin (biomarkers of cell death and barrier integrity). Follow-up of a subset of these patients greater than 1-year post-COVID19 indicated these abnormalities resolved over time. Collectively, these data indicate that COVID-19 results in a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells.HighlightsThe post-COVID19 airway is characterized by increased cytotoxic lymphocytes.Distinct airway proteomes are associated with the airway immune cell landscape.The peripheral blood does not predict immune-proteome alterations in the airway post-COVID19.Persistent abnormalities in the airway immune-proteome post-COVID19 airways correlate with ongoing epithelial damage.

BackgroundFibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airway remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD and assessed association with disease severity and outcome.MethodsBronchoalveolar lavage (BAL) was collected from a cohort of fILD patients and total airway antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 124 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.ResultsA subset of patients with fILD but not healthy controls had a local autoimmune signature in their airways that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased airway total IgA and IgG1 while subjects with CHP had increased airway IgA, IgG1 and IgG4. In patients with CHP, increased airway total IgA was associated with reduced survival probability.ConclusionThe presence of airway autoantibodies identifies a unique subset of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.

BackgroundFibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airways remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD, and assessed association with disease severity and outcome.MethodsBronchoalveolar lavage (BAL) fluid was collected from a cohort of fILD patients and total BAL antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 122 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.ResultsA subset of patients with fILD but not healthy controls had a local autoimmune signature in their BAL that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased BAL total IgA and IgG1 while subjects with CHP had increased BAL IgA, IgG1 and IgG4. In patients with CHP, increased BAL total IgA was associated with reduced survival probability.ConclusionAirway autoantibodies that are not present systemically identify a group of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.

Rationale: Airway macrophages (AMs) are key regulators of the lung environment and are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease with no cure. However, knowledge about the epigenetics of AMs in IPF is limited. Objectives: To assess the role of epigenetic regulation of AMs during lung fibrosis. Methods: We undertook DNA methylation (DNAm) profiling by using Illumina EPIC (850k) arrays in sorted AMs from healthy donors (n = 14) and donors with IPF (n = 30). Cell-type deconvolution was performed by using reference myeloid-cell DNA methylomes. Measurements and Main Results: Our analysis revealed that epigenetic heterogeneity was a key characteristic of IPF AMs. DNAm "clock" analysis indicated that epigenetic alterations in IPF AMs were not associated with accelerated aging. In differential DNAm analysis, we identified numerous differentially methylated positions (n = 11) and differentially methylated regions (n = 49) between healthy and IPF AMs, respectively. Differentially methylated positions and differentially methylated regions encompassed genes involved in lipid (LPCAT1 [lysophosphatidylcholine acyltransferase 1]) and glucose (PFKFB3 [6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3]) metabolism, and importantly, the DNAm status was associated with disease severity in IPF. Conclusions: Collectively, our data identify that changes in the epigenome are associated with the development and function of AMs in the IPF lung.

Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating, scarring lung disease with a worse prognosis than some cancers. The incidence of IPF is increasing and while current antifibrotic therapies slow disease progression, they do not offer a cure. The pathobiology of IPF is complex and is driven by aging-associated cellular dysfunction, epithelial injury, and an aberrant wound-healing response characterised by fibroblast activation and extracellular matrix accumulation (ECM) in the interstitium. As understanding of the underlying mechanisms has evolved, new targets for pharmacotherapy have emerged. Novel drugs currently in development for pulmonary fibrosis have diverse molecular properties and mechanisms of action, as well as different routes of administration. A shared primary goal of these agents is reduction of the profibrotic activity of fibroblasts and limitation of ECM deposition, which hinders gas exchange and ultimately leads to respiratory failure. This article provides an overview of some promising new therapeutic options for IPF and considers the challenges for future drug development.

In a context of political and economic austerity, social innovation has been presented as a solution to many social challenges, old and new. It aims to support the introduction of new ideas in response to the current urgent needs and challenges of vulnerable groups and seems to offer promising solutions to the challenges faced by rural areas. Yet the evidence base of the impacts on the sustainable development of rural communities remains scarce. In this paper, we explore social innovation in the context of community forestry and provide a brief synthetic review of key themes linking the two concepts. We examine a case of social innovation in the context of community forestry and analyse its type, extent, and scale of impact in a marginalized rural area of Scotland. Using an in-depth case study approach, we apply a mixed research methodology using quantitative indicators of impact as well as qualitative data. Our results show that social innovation reinforces the social dimension of community forestry. Impacts are highlighted across domains (environmental, social, economic, and institutional/governance) but are mainly limited to local territory. We discuss the significance of those results in the context of community forestry as well as for local development. We formulate policy recommendations to foster and sustain social innovation in rural areas.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease of unknown aetiology. There is growing evidence that the lung microbiota may play a role in IPF. However, no study has investigated the functional impact of the short-chain fatty acids (SCFAs) on primary bronchial epithelial cells (PBECs) and disease pathogenesis. Therefore, we investigated the influence of acetate, propionate, and butyrate on PBECs from healthy controls and subjects with IPF. Subjects diagnosed with IPF (n=201) and healthy controls (n=40) were prospectively recruited and underwent bronchoalveolar lavage. Bacterial DNA was isolated and 16S rRNA gene sequencing undertaken to characterise bacterial communities. Untargeted 1H nuclear magnetic resonance spectroscopy-based metabolomics and targeted gas chromatography-mass spectrometry captured the metabolic profile of these samples. PBECs from healthy controls and subjects with IPF were differentiated at air-liquid interface (ALI) and either left untreated or exposed to the SCFAs. The IPF microbiota was less diverse (P Subjects with IPF display an altered microbiome which is associated with a distinct metabolic signature in the lower airways. Differences in specific bacterial genera and an increased bacterial burden in IPF results in changes in the SCFAs in the airways. In vitro work demonstrates the potential of these SCFAs to shape immunological responses in the lung, mediating the pathogenesis of fibrosis.

We aim to contribute to in-depth comprehension of the factors and preferences behind the reuses of large-scale underused or abandoned former collective farms from the 1950s–1980s for biogas plants and solar photovoltaic power plants. As a case study, three regions in the southern part of the Czech Republic have been selected. Our findings signal that the residents’ attitudes towards the mentioned energy sources are rather negative. Similarly, farmers’ interest in photovoltaic power plants is low. More interest has been detected in the case of biogas production; this is especially true for large agricultural companies and farmers, who own underused or abandoned premises. Biogas plants are frequently located in agricultural areas with warmer or just slightly colder climates as a consequence of the potential to process locally grown maize. On the other hand, photovoltaic power plants are found on more fertile plains with high levels of insolation, but, surprisingly, also in mountain regions which typically have low emissions. Both renewable energy solutions were found to be problematic as there is strong opposition to both types of installations among local inhabitants. This indicates the need for “soft” forms of planning. Stakeholder engagement and inclusive participation in all phases of the planning process are essential requirements for arriving at the best possible outcomes for the new renewable energy solutions and their acceptance by the public.

The 2015 Paris Agreement is falling short of its aspirations, as signatory countries are struggling to implement the policies required to meet the targets. The global scenario framework formed by the Shared Socioeconomic Pathways (SSPs) and the Representative Concentration Pathways (RCPs) places little emphasis on the dynamics of climate policy implementation. Social science approaches to understanding these dynamics are not well-integrated into climate scenario research. We apply an implementation research approach to analyse the transition to clean energy in the US and China, as well as two examples from Europe–Germany and Spain–which have shown markedly diverging implementation trajectories. We propose four implementation scenarios (ISs) for clean energy worldwide which relate to different configurations of actors in the policy system. These are: (1) Civil Society Takes Control (IS1)–where ideologically opposed governments are marginalised by citizens and forward-thinking investors; (2) Strong-arm Transition (IS2)–where a single party state drives the transition without the involvement of civil society; (3) Systemic Limits (IS3)–which highlights the need to focus on the whole energy system, not just renewables; and (4) Renewable Austerity (IS4)–where an economic downturn offers powerful anti-transition actors the opportunity to advocate removal of support for climate mitigation, as they did after the 2007–2008 financial crisis. This scenario could be repeated as countries seek to recover from the Covid-19 pandemic. Our study offers a framework for structured analysis of real-world constraints faced by implementing actors, which we argue is urgently needed to help national and international policy makers achieve climate goals. Key policy insights The world is struggling to implement the Paris Agreement, partly because the complex dynamics of climate policy implementation are poorly understood. Social science approaches to understanding these dynamics are not well-integrated into climate scenario research. Implementation research focussing on the actors and context provides a useful framework for analysis of implementation efforts from major global carbon emitters. The approach offers new and distinctive scenario narratives that go beyond Representative Concentration Pathways (RCPs) and Shared Socioeconomic Pathways (SSPs). These new scenarios can help policy makers evaluate likely outcomes of climate policy implementation based on information about actors and context. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Airway macrophages (AMs) are key regulators of the lung environment and are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease with no cure. However, the epigenetics of AMs development and function in IPF are limited. Here, we characterised the DNA-methylation (DNAm) profile of AMs from IPF (n=30) and healthy (n=14) donors. Our analysis revealed epigenetic heterogeneity was a key characteristic of IPF AMs. DNAm ‘clock’ analysis indicated epigenetic alterations in IPF-AMs was not associated with accelerated ageing. In differential DNAm analysis, we identified numerous differentially methylated positions (DMPs, n=11) and regions (DMRs, n=49) between healthy and IPF AMs respectively. DMPs and DMRs encompassed genes involved in lipid (LPCAT1) and glucose (PFKB3) metabolism and importantly, DNAm status was associated with disease severity in IPF. Collectively, our data identify that profound changes in the epigenome underpin the development and function of AMs in the IPF lung.

Spatial planning systems at local and regional levels are often not well-adapted to the growth of small-scale and local social innovations in renewable energy. Participatory decision support tools have been developed to support the implementation of many areas of environmental policy, but are less common in energy contexts. In response to this knowledge gap, we discuss, compare and contrast the participatory development of two different types of digital support tools for the cases of Spain and the Netherlands, leading to insights into the characteristics that local-level stakeholders find particularly desirable. We adopt an integrative approach, hybridizing implementation theory and action research for, respectively, analysis of implementation characteristics of key actors, and knowledge co-construction with participant stakeholders. The tools developed represent two extremes of the spatial decision support tool spectrum, a simple touchscreen application on the one hand (COLLAGE) and a more complicated spatial model on the other (APoLUS). COLLAGE was used and well-liked by stakeholders, whereas APoLUS was not adopted by the participant group, who nevertheless contributed much essential information to its development. We identify eight key differences between the two tools which shed light on the nature of bottom-up energy transition processes: 1: Target users; 2: Target scale of action; 3: Relevance to users’ needs; 4: Interactive quality; 5: Key emphasis; 6: Level of complexity; 7: Ease of communication of tool rationale; 8: Cost. The differences between these tools also relate to a recognized dichotomy in sustainability transition research, with complex spatial support systems like APoLUS tending towards descriptive-analytical modes of sustainability science and simpler tools like COLLAGE being more clearly related to transformational modes. Approaches to supporting local-scale energy transitions that are able to span both modes are likely to become increasingly relevant as the climate crisis evolves. We also identify a research gap between support tools for implementation of established policy and support tools for transformative actions at local scales, and suggest the study of digital “transition support tools” as a promising avenue for future research. Highlights •Participatory decision support tools can help support local scale social innovation in energy.•Different types of tools address different modes of sustainability science (descriptive-analytical vs transformational).•As multi-level, multi-actor processes, energy transitions require participatory support approaches that span both modes.•Simple touch-screen tools can aid local scale implementation, while more complex models are useful for strategic planning.•The study of digital “transition support tools” is a promising avenue for future research.

Social innovation is a process in which local communities build social and cultural capital to address challenges and social needs. The diffusion of social innovation requires compelling narratives that encourage people to join them. Using qualitative techniques and a multiple case study methodology, this paper examines the content of narratives of social innovation in rural areas and how actors construct, spread and change them. We propose a narrative analytical framework comprising four key components: problematisation; solutions and goals; actors; and plot, which we apply to three initiatives in Scotland and Spain. Our findings suggest that marginalisation, the natural environment and community activation are central themes in the content of narratives. In addition, we explain how policies and public actors can support social innovation as well as how collective leadership of social innovations can reduce imbalances in power relations, and contribute to a consistent evolution of narratives over time, enhancing the sustainability of social innovation projects overall. Supporting Information

RATIONALE: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises following repeated exposure and sensitisation to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease but to date, no study has investigated the composition of microbial communities in the lower airways in CHP. OBJECTIVE: To characterise and compare the airway microbiome in subjects with CHP, idiopathic pulmonary fibrosis (IPF) and controls. METHODS: We prospectively recruited individuals diagnosed with CHP (n=110), IPF (n=45) and controls (n=28). Subjects underwent bronchoalveolar lavage and bacterial DNA was isolated, quantified by qPCR and the 16S rRNA gene was sequenced to characterise the bacterial communities in the lower airways. MAIN MEASUREMENTS AND RESULTS: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both IPF and CHP subjects included Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. However, in IPF, Firmicutes dominated while the percentage of reads assigned to Proteobacteria in the same group was significantly lower compared to CHP subjects. At the genus level, Staphylococcus was increased in CHP and Actinomyces and Veillonella in IPF. The lower airway bacterial burden in CHP subjects was higher than controls but lower than those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP. CONCLUSIONS: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF and, notably, bacterial burden in individuals with CHP fails to predict survival.

Current estimates suggest that the world is on track for ~3°C of heating relative to pre-industrial levels by 2100. This is likely to bring great disruption to earth systems, leading to increased natural hazard risks, crop failures, civil unrest and population migration. There is, however, a high degree of uncertainty about the impacts that such events may have on land use and ecosystems in individual countries. Integrated assessment modelling (IAM) of scenarios like the Shared Socioeconomic Pathways (SSPs) offers one way to address this uncertainty, allowing outcomes such as the relative land cover under food production or forestry to be compared for each scenario. However, global and continental-scale IAMs need to be complemented by landscape scale spatial modelling to inform national and regional policy making. In this paper, we demonstrate impacts and trade-offs of future land cover change in Scotland, a UK region with a high degree of political autonomy, using downscaled SSPs from Europe to the national and finally the regional level. Our methods integrate participatory knowledge co-construction approaches with land-use modelling. Firstly, a stakeholder workshop held in November 2018 led to the development of detailed narratives for 5 UK SSPs. Two contrasting UK SSPs, SSP1 (Sustainability), and SSP5 (Fossil-Fuelled Development) were then adapted to the case of Scotland and simulated to the year 2040 using a land use change model (APoLUS). Land use demands for each scenario were quantified based on historical tendencies, narrative information derived from the workshop, and future Scottish Government targets. Results highlight trade-offs between forest cover, grasslands, natural areas including marginal peatlands important for carbon sequestration, and cropland for food production and the drinks industry. We discuss these preliminary findings, highlight key areas of uncertainty and present pathways for future work.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease in which airway macrophages (AMs) play a key role. Itaconate has emerged as a mediator of macrophage function, but its role during fibrosis is unknown. Here, we reveal that itaconate is an endogenous antifibrotic factor in the lung. Itaconate levels are reduced in bronchoalveolar lavage, and itaconate-synthesizing cis-aconitate decarboxylase expression (ACOD1) is reduced in AMs from patients with IPF compared with controls. In the murine bleomycin model of pulmonary fibrosis, Acod1-/- mice develop persistent fibrosis, unlike wild-type (WT) littermates. Profibrotic gene expression is increased in Acod1-/- tissue-resident AMs compared with WT, and adoptive transfer of WT monocyte-recruited AMs rescued mice from disease phenotype. Culture of lung fibroblasts with itaconate decreased proliferation and wound healing capacity, and inhaled itaconate was protective in mice in vivo. Collectively, these data identify itaconate as critical for controlling the severity of lung fibrosis, and targeting this pathway may be a viable therapeutic strategy.

Chronic hypersensitivity pneumonitis (CHP) is a scarring lung disease that arises following repeated exposure to antigens. While the lung microbiome is increasingly implicated in respiratory disease, to date, no study has investigated the composition of microbial communities and metabolites in the lower airways in CHP. We prospectively recruited individuals diagnosed with CHP (n=110), idiopathic pulmonary fibrosis (IPF) (n=45) and controls (n=28). Subjects underwent bronchoalveolar lavage with differential cell counts. Bacterial DNA was isolated, quantified by qPCR and 16S rRNA gene sequencing performed to characterise bacterial communities. 1H Nuclear Magnetic Resonance spectroscopy was utilised to capture the metabolic profile of these individuals. Lymphocyte and neutrophil proportions were higher in CHP and IPF, respectively. Evident alterations in the composition and microbial community structure (β-diversity) of the respiratory microbiome were observed in CHP compared to IPF; Staphylococcus was increased in CHP and Actinomyces and Veillonella in IPF. There was an increased bacterial burden in cases compared to controls. Individuals with CHP had significantly reduced α-diversity and bacterial load compared to subjects with IPF. Metabolomics analysis revealed decreased levels of the short-chain fatty acids acetate, propionate and butyrate in CHP compared to IPF. Subjects with CHP and IPF displayed an altered microbiome and a distinct metabolic signature in the lower airways. Collectively, differences in specific bacterial genera may provide a low-level antigenic stimulus for repetitive alveolar injury. Further elucidation of these differences will improve our understanding of crosstalk between microbe and host and its role in the progression of fibrosis.

Introduction a Objectives: Airway macrophages (AMs) are implicated in the dysregulated wound healing response in idiopathic pulmonary fibrosis (IPF). The endogenous metabolite itaconate, synthesised by immune-response gene 1 (IRG1), has been shown to influence macrophage function via regulation of succinate dehydrogenase. Here we investigated the role of itaconate in pulmonary fibrosis. Methods: To assess the expression pattern of Irg1 in the lung, we analysed gene expression in AMs from IPF patients or controls. To investigate the role of itaconate in the bleomycin model of pulmonary fibrosis we utilised WT and Irg1-/- mice, in addition to therapeutic dosing of exogenous itaconate. To determine the role of secreted itaconate on the stromal compartment in IPF, primary lung fibroblasts were cultured with itaconate in vitro and proliferation/wound healing was assessed. Results: Irg1 expression was reduced in IPF AMs compared to controls. In the bleomycin model, Irg1-/- mice had decreased survival, worsened lung function and increased collagen deposition at the resolution time point (42d post bleomycin). Tissue-resident AMs (Tr-AMs) upregulated the expression of fibrosis-related genes in Irg1-/- mice and showed impaired Oxidative Phosphorylation. Inhaled itaconate during the fibrotic phase of the bleomycin model improved lung function and decreased gene expression of type IV collagen and fibronectin. In vitro culture of primary human lung fibroblasts with itaconate decreased proliferation and wound healing capacity. Conclusions: Overall these data indicate that itaconate is essential for the resolution of lung fibrosis and that targeting this pathway may be a viable therapeutic strategy in IPF.

To meet the goals of the Paris Agreement, as well as earlier targets set down in the EU Low-Carbon Road Map, requires a major transformation in the way energy is generated, marketed, and distributed that we call the clean energy transition. The clean energy transition is a social process and its success will be determined by the actions of key actors such as policy makers, energy suppliers and businesses. In this paper, we apply integrative research approaches to engage stakeholders in the renewable energy (RE) sector in knowledge co-construction activities for the case of Spain. Established modes of energy production are very resilient and powerful actors are effectively blocking the energy transition on the basis that it threatens the status quo. Innovation is unlikely unless that veto can be overcome. The work has implications elsewhere, especially for other EU countries, where institutional structures and power relations are similar to those in Spain. To move forward requires a better understanding of the clean energy transition as a social process, and in particular, systematic identification of barriers to innovation and a serious effort to negotiate with the most powerful players.

In the postulated efforts to limit adverse climate change (CC), increasing attention is paid to the development of distributed renewable energy (RE) that meets the needs of local communities on the spot. This article analyses the objectives, planned actions and performance indicators related to CC and RE, defined by national and local stakeholders in: (1) the national Rural Development Programme (RDP) 2014–2020 in Poland and (2) in the bottom-up Local Development Strategies (LDS) financed from RDP and using a Community-Led Local Development approach. The content analysis method was used. We found that the strategy documents considered, created in the years 2014–2015, paid relatively little attention to local actions related to CC and RE. Some educational activities related to adaptation and mitigation of CC were planned in 66% of LDS, while investment support for RE was planned only in 9% of the LDS. Traditional goals such as supporting local businesses and farmers, local cultural heritage and the development of human and social capital were seen as more important. The results of the analysis suggest a relatively low level of interest from rural-policy actors in Poland in implementing the climate-friendly objectives of the Europe 2020 strategy. This article contributes to understanding why Poland failed to meet the European 2020 RE development goals. These issues are discussed in the context of national and continental climate policy and problems of transformation to post-carbon society.