Participation in Transition(s):Reconceiving Public Engagements in Energy Transitions as Co-Produced, Emergent and Diverse

This paper brings the transitions literature into conversation with constructivist Science and Technology Studies (STS) perspectives on participation for the first time. In doing so we put forward a conception of public and civil society engagement in sustainability transitions as co-produced, relational, and emergent. Through paying close attention to the ways in which the subjects, objects, and procedural formats of public engagement are constructed through the performance of participatory collectives, our approach offers a framework to open up to and symmetrically compare diverse and interconnected forms of participation that make up wider socio-technical systems. We apply this framework in a comparative analysis of four diverse cases of civil society involvement in UK low carbon energy transitions. This highlights similarities and differences in how these distinct participatory collectives are orchestrated, mediated, and subject to exclusions, as well as their effects in producing particular visions of the issue at stake and implicit models of participation and ‘the public’. In conclusion we reflect on the value of this approach for opening up the politics of societal engagement in transitions, building systemic perspectives of interconnected ‘ecologies of participation’, and better accounting for the emergence, inherent uncertainties, and indeterminacies of all forms of participation in transitions

Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.

Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.L.S.C.L. was funded by Wellcome Trust (104384/Z/14/Z). M.R.C. is supported by National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Chan-Zuckerburg Initiative Human Cell Atlas Technology Development Grant, Medical Research Council New Investigator Research Grant (MR/N024907/1), Arthritis Research UK Cure Challenge Research Grant (21777), and NIHR Research Professorship (RP-2017-08- ST2-002)

Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome.

RATIONALE: Acute respiratory distress syndrome (ARDS) affects over 200000 people annually in the USA. Despite causing severe, and often refractory, hypoxaemia, the high mortality and long-term morbidity of ARDS results mainly from extra-pulmonary organ failure; however the mechanism for this organ crosstalk has not been determined. METHODS: Using autologous radiolabelled neutrophils we investigated the pulmonary transit of primed and unprimed neutrophils in humans. Flow cytometry of whole blood samples was used to assess transpulmonary neutrophil priming gradients in patients with ARDS, sepsis and perioperative controls. MAIN RESULTS: Unprimed neutrophils passed through the lungs with a transit time of 14.2 s, only 2.3 s slower than erythrocytes, and with <5% first-pass retention. Over 97% of neutrophils primed ex vivo with granulocyte macrophage colony-stimulating factor were retained on first pass, with 48% still remaining in the lungs at 40 min. Neutrophils exposed to platelet-activating factor were initially retained but subsequently released such that only 14% remained in the lungs at 40 min. Significant transpulmonary gradients of neutrophil CD62L cell surface expression were observed in ARDS compared with perioperative controls and patients with sepsis. CONCLUSIONS: We demonstrated minimal delay and retention of unprimed neutrophils transiting the healthy human pulmonary vasculature, but marked retention of primed neutrophils; these latter cells then 'deprime' and are re-released into the systemic circulation. Further, we show that this physiological depriming mechanism may fail in patients with ARDS, resulting in increased numbers of primed neutrophils within the systemic circulation. This identifies a potential mechanism for the remote organ damage observed in patients with ARDS.This work was supported by the Wellcome Trust, MRC (UK), Papworth Hospital R&D, Intensive Care Society and NIHR Cambridge Biomedical Research Centre.This is the final published version, also available from http://thorax.bmj.com/content/early/2014/04/04/thoraxjnl-2013-204742.full

A case-control study of cryptorchidism and maternal hormone concentrations in early pregnancy.

Serum samples taken between 6 and 20 weeks of gestation were obtained from 28 mothers who gave birth to cryptorchid sons (cases) and from 108 control mothers. In comparison with controls the cases had 10% higher geometric mean oestradiol (95% CI -13% to +39%: P=0.42) and 10% lower geometric mean testosterone (95% CI -27% to +10%: P=0.30). Among the samples collected between 6 and 14 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 5% lower (95% CI -32% to +31%: P=0.74) and 25% lower (95% CI -45% to +1%: P=0.06) respectively in cases than in controls. Among the samples collected between 15 and 20 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 29% higher (95% CI -8% to +79%: P=0.14) and 21% higher (95% CI -8% to +60%: P=0.18) respectively in cases than in controls. The results do not support the hypothesis that cryptorchidism may be caused by high concentrations of oestradiol in the maternal blood during the first phase of testicular descent, but suggest that the possible association of cryptorchidism with low maternal testosterone during early gestation should be further investigated

Incidence and recognition of acute respiratory distress syndrome in a UK intensive care unit.

The reported incidence of ARDS is highly variable (2.5%-19% of intensive care unit (ICU) patients) and varies depending on study patient population used. We undertook a 6-month, prospective study to determine the incidence and outcome of ARDS in a UK adult University Hospital ICU. 344 patients were admitted during the study period, of these 43 (12.5%) were determined to have ARDS. Patients with ARDS had increased mortality at 28 days and 2 years post-diagnosis, and there was under-recognition of ARDS in both medical records and death certificattion. Our findings have implications for critical care resource planning.This is the final version of the article. It first appeared from BMJ Thorax via ://dx.doi.org/10.1136/thoraxjnl-2016-20840

Understanding the impact of diet and nutrition on symptoms of Tourette Syndrome: A Scoping Review

This document is the accepted manuscript version. The final, definitive version of this paper has been published in Journal of Child Health Care, December 2017, published by SAGE Publishing, doi:https://doi.org/10.1177/1367493517748373.Anecdotal reports frequently suggest some dietary involvement in the maintenance of tics in children with Tourette syndrome (TS). This scoping review aimed to (1) understand the possible influence of diet as a trigger of tics and (2) map out the existing studies documenting dietary interventions in children with TS. Current evidence suggests no single diet to benefit individuals with TS. However, reports from parents of children with TS suggest that certain allergens in food may exacerbate tic-related symptoms. For example, an increase in tics has been related to the consumption of caffeine and refined sugar. Moreover, oligoantigenic diets and sugar-free diets have been identified as significantly reducing tics. More research is urgently needed to develop more accurate guidance for parents and children with TS, as many have reported using dietary and nutritional supplements, despite the lack of evidence detailing any benefits, side effects and recommended doses.Peer reviewedFinal Accepted Versio

Deliberating stratospheric aerosols for climate geoengineering and the SPICE project

Increasing concerns about the narrowing window for averting dangerous climate change have prompted calls for research into geoengineering, alongside dialogue with the public regarding this as a possible response. We report results of the first public engagement study to explore the ethics and acceptability of stratospheric aerosol technology and a proposed field trial (the Stratospheric Particle Injection for Climate Engineering (SPICE) ‘pipe and balloon’ test bed) of components for an aerosol deployment mechanism. Although almost all of our participants were willing to allow the field trial to proceed, very few were comfortable with using stratospheric aerosols. This Perspective also discusses how these findings were used in a responsible innovation process for the SPICE project initiated by the UK’s research councils

Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model

Efficient T-cell targeting, infiltration and activation within tumors is crucial for successful adoptive T-cell therapy. Intravital microscopy is a powerful tool for the visualization of T-cell behavior within tumors, as well as spatial and temporal heterogeneity in response to immunotherapy. Here we describe an experimental approach for intravital imaging of adoptive T-cell morphology, mobility and trafficking in a skin-flap tumor model, following immune modulation with immune checkpoint inhibitors (ICIs) targeting PD-L1 and CTLA-4. A syngeneic model of ovalbumin and mCherry-expressing amelanotic mouse melanoma was used in conjunction with adoptively transferred OT-1+ cytotoxic T-cells expressing GFP to image antigen-specific live T-cell behavior within the tumor microenvironment. Dynamic image analysis of T-cell motility showed distinct CD8+ T-cell migration patterns and morpho-dynamics within different tumor compartments in response to ICIs: this approach was used to cluster T-cell behavior into four groups based on velocity and meandering index. The results showed that most T-cells within the tumor periphery demonstrated Lévy-like trajectories, consistent with tumor cell searching strategies. T-cells adjacent to tumor cells had reduced velocity and appeared to probe the local environment, consistent with cell-cell interactions. An increased number of T-cells were detected following treatment, traveling at lower mean velocities than controls, and demonstrating reduced displacement consistent with target engagement. Histogram-based analysis of immunofluorescent images from harvested tumors showed that in the ICI-treated mice there was a higher density of CD31+ vessels compared to untreated controls and a greater infiltration of T-cells towards the tumor core, consistent with increased cellular trafficking post-treatment