Are Regions Important in British Elections? Valence Politics and Local Economic Contexts at the 2010 General Election

Pattie C. J., Johnston R. J., Schipper M. and Potts L. Are regions important in British elections? Valence politics and local economic contexts at the 2010 General Election, Regional Studies. Electoral support for major parties is influenced by judgements of economic performance. This helps account for electoral geographies, as economic conditions vary spatially. Past work, concentrating on objective economic indicators or on voters' personal economic evaluations, suggested that contextual effects work most powerfully when very local, suggesting that regional voting trends are artefacts of more intimate geographies. This paper extends that work by examining how voters' decisions are influenced by the economic evaluations of others in their communities and demonstrates that some contextual effects, at least, really are more powerful at the regional than at more local scales

Adipocytes harbor a glucosylceramide biosynthesis pathway involved in iNKT cell activation

Background: Natural killer T (NKT) cells in adipose tissue (AT) contribute to whole body energy homeostasis. Results: Inhibition of the glucosylceramide synthesis in adipocytes impairs iNKT cell activity. Conclusion: Glucosylceramide biosynthesis pathway is important for endogenous lipid antigen activation of iNKT cells in adipocytes.Significance: Unraveling adipocyte-iNKT cell communication may help to fight obesity-induced AT dysfunction.Overproduction and/or accumulation of ceramide and ceramide metabolites, including glucosylceramides, can lead to insulin resistance. However, glucosylceramides also fulfill important physiological functions. They are presented by antigen presenting cells (APC) as endogenous lipid antigens via CD1d to activate a unique lymphocyte subspecies, the CD1d-restricted invariant (i) natural killer T (NKT) cells. Recently, adipocytes have emerged as lipid APC that can activate adipose tissue-resident iNKT cells and thereby contribute to whole body energy homeostasis. Here we investigate the role of the glucosylceramide biosynthesis pathway in the activation of iNKT cells by adipocytes.UDP-glucose ceramide glucosyltransferase (Ugcg), the first rate limiting step in the glucosylceramide biosynthesis pathway, was inhibited via chemical compounds and shRNA knockdown in vivo and in vitro. beta-1,4-Galactosyltransferase (B4Galt) 5 and 6, enzymes that convert glucosylceramides into potentially inactive lactosylceramides, were subjected to shRNA knock down. Subsequently, (pre)adipocyte cell lines were tested in co-culture experiments with iNKT cells (IFN gamma and 114 secretion).Inhibition of Ugcg activity shows that it regulates presentation of a considerable fraction of lipid self-antigens in adipocytes. Furthermore, reduced expression levels of either B4Galt5 or -6, indicate that B4Galt5 is dominant in the production of cellular lactosylceramides, but that inhibition of either enzyme results in increased iNKT cell activation. Additionally, in vivo inhibition of Ugcg by the aminosugar AMP-DNM results in decreased iNKT cell effector function in adipose tissue.Inhibition of endogenous glucosylceramide production results in decreased iNKT cells activity and cytokine production, underscoring the role of this biosynthetic pathway in lipid self-antigen presentation by adipocytes

Adipocytes harbor a glucosylceramide biosynthesis pathway involved in iNKT cell activation

Background: Natural killer T (NKT) cells in adipose tissue (AT) contribute to whole body energy homeostasis. Results: Inhibition of the glucosylceramide synthesis in adipocytes impairs iNKT cell activity. Conclusion: Glucosylceramide biosynthesis pathway is important for endogenous lipid antigen activation of iNKT cells in adipocytes.Significance: Unraveling adipocyte-iNKT cell communication may help to fight obesity-induced AT dysfunction.Overproduction and/or accumulation of ceramide and ceramide metabolites, including glucosylceramides, can lead to insulin resistance. However, glucosylceramides also fulfill important physiological functions. They are presented by antigen presenting cells (APC) as endogenous lipid antigens via CD1d to activate a unique lymphocyte subspecies, the CD1d-restricted invariant (i) natural killer T (NKT) cells. Recently, adipocytes have emerged as lipid APC that can activate adipose tissue-resident iNKT cells and thereby contribute to whole body energy homeostasis. Here we investigate the role of the glucosylceramide biosynthesis pathway in the activation of iNKT cells by adipocytes.UDP-glucose ceramide glucosyltransferase (Ugcg), the first rate limiting step in the glucosylceramide biosynthesis pathway, was inhibited via chemical compounds and shRNA knockdown in vivo and in vitro. beta-1,4-Galactosyltransferase (B4Galt) 5 and 6, enzymes that convert glucosylceramides into potentially inactive lactosylceramides, were subjected to shRNA knock down. Subsequently, (pre)adipocyte cell lines were tested in co-culture experiments with iNKT cells (IFN gamma and 114 secretion).Inhibition of Ugcg activity shows that it regulates presentation of a considerable fraction of lipid self-antigens in adipocytes. Furthermore, reduced expression levels of either B4Galt5 or -6, indicate that B4Galt5 is dominant in the production of cellular lactosylceramides, but that inhibition of either enzyme results in increased iNKT cell activation. Additionally, in vivo inhibition of Ugcg by the aminosugar AMP-DNM results in decreased iNKT cell effector function in adipose tissue.Inhibition of endogenous glucosylceramide production results in decreased iNKT cells activity and cytokine production, underscoring the role of this biosynthetic pathway in lipid self-antigen presentation by adipocytes

Sars-cov-2 entry into human airway organoids is serine protease-mediated and facilitated by the multibasic cleavage site

Coronavirus entry is mediated by the spike protein that binds the receptor and mediates fusion after cleavage by host proteases. The proteases that mediate entry differ between cell lines, and it is currently unclear which proteases are relevant in vivo. A remarkable feature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is the presence of a multibasic cleavage site (MBCS), which is absent in the SARS-CoV spike. Here, we report that the SARS-CoV-2 spike MBCS increases infectivity on human airway organoids (hAOs). Compared with SARS-CoV, SARS-CoV-2 entered faster into Calu-3 cells and, more frequently, formed syncytia in hAOs. Moreover, the MBCS increased entry speed and plasma membrane serine protease usage relative to cathepsin-mediated endosomal entry. Blocking serine proteases, but not cathepsins, effectively inhibited SARS-CoV-2 entry and replication in hAOs. Our findings demonstrate that SARS-CoV-2 enters relevant airway cells using serine proteases, and suggest that the MBCS is an adaptation to this viral entry strategy

Hen Harrier Circus cyaneus nest sites on the Isle of Mull are associated with habitat mosaics and constrained by topography

This is an Accepted Manuscript of an article published by Taylor & Francis in Bird Study on 07/02/2018, available online: http://www.tandfonline.com/doi/full/10.1080/00063657.2017.1421611Capsule: Hen Harrier on the Isle of Mull, UK, are associated with habitat mosaics consisting of moorland, scrub and forestry but avoid grazed land, suggesting that forested habitats could be managed sympathetically for Hen Harrier in the future should the current UK population increase. Aims: To use distribution modelling to investigate nesting habitat associations using a long term dataset for Hen Harrier on Mull. Methods: We develop area-interaction models using a LASSO penalty to explore the distribution of 102 Hen Harrier nest sites in relation to habitat and topography. Our model is then successfully validated in tests using data for 70 nest sites from subsequent years. Results: Our model is effective in predicting suitable areas for Hen Harrier nest sites and indicates that Hen Harriers on Mull are found in habitat mosaics below 200 m asl. Hen Harrier nest intensity is positively associated with increasing proportions of moorland and scrub, open canopy forestry and closed canopy forestry. Nest intensity is negatively associated with increasing proportions of grazed land. Conclusion: Hen Harrier avoid grazed areas but are relatively tolerant of other habitat combinations. These findings are supported by previous observations of Hen Harrier habitat use and have implications for the recovery of some Hen Harrier SPA populations and future forest management. Open canopy forest and forest mosaics could potentially be incorporated into landscape-scale conservation plans for Hen Harriers using the population in Mull as an example

The impact of regionalized trauma care on the distribution of severely injured patients in the Netherlands

Background Twenty years ago, an inclusive trauma system was implemented in the Netherlands. The goal of this study was to evaluate the impact of structured trauma care on the concentration of severely injured patients over time. Methods All severely injured patients (Injury Severity Score [ISS] >= 16) documented in the Dutch Trauma Registry (DTR) in the calendar period 2008-2018 were included for analysis. We compared severely injured patients, with and without severe neurotrauma, directly brought to trauma centers (TC) and non-trauma centers (NTC). The proportion of patients being directly transported to a trauma center was determined, as was the total Abbreviated Injury Score (AIS), and ISS. Results The documented number of severely injured patients increased from 2350 in 2008 to 4694 in 2018. During this period, on average, 70% of these patients were directly admitted to a TC (range 63-74%). Patients without severe neurotrauma had a lower chance of being brought to a TC compared to those with severe neurotrauma. Patients directly presented to a TC were more severely injured, reflected by a higher total AIS and ISS, than those directly transported to a NTC. Conclusion Since the introduction of a well-organized trauma system in the Netherlands, trauma care has become progressively centralized, with more severely injured patients being directly presented to a TC. However, still 30% of these patients is initially brought to a NTC. Future research should focus on improving pre-hospital triage to facilitate swift transfer of the right patient to the right hospital.Trauma Surger

Dutch trauma system performance: are injured patients treated at the right place?

Background: The goal of trauma systems is to match patient care needs to the capabilities of the receiving centre. Severely injured patients have shown better outcomes if treated in a major trauma centre (MTC). We aimed to evaluate patient distribution in the Dutch trauma system. Furthermore, we sought to identify factors associated with the undertriage and transport of severely injured patients (Injury Severity Score (ISS) >15) to the MTC by emergency medical services (EMS).Methods: Data on all acute trauma admissions in the Netherlands (2015-2016) were extracted from the Dutch national trauma registry. An ambulance driving time model was applied to calculate MTC transport times and transport times of ISS >15 patients to the closest MTC and non-MTC. A multivariable logistic regression analysis was performed to identify factors associated with ISS >15 patients' EMS undertriage to an MTC.Results: Of the annual average of 78,123 acute trauma admissions, 4.9% had an ISS >15. The nonseverely injured patients were predominantly treated at non-MTCs (79.2%), and 65.4% of patients with an ISS >15 received primary MTC care. This rate varied across the eleven Dutch trauma networks (36.8%-88.4%) and was correlated with the transport times to an MTC (Pearson correlation -0.753, p=0.007). The trauma networks also differed in the rates of secondary transfers of ISS >15 patients to MTC hospitals (7.8% 59.3%) and definitive MTC care (43.6% - 93.2%). Factors associated with EMS undertriage of ISS >15 patients to the MTC were female sex, older age, severe thoracic and abdominal injury, and longer additional EMS transport times.Conclusions: Approximately one-third of all severely injured patients in the Netherlands are not initially treated at an MTC. Special attention needs to be directed to identifying patient groups with a high risk of undertriage. Furthermore, resources to overcome longer transport times to an MTC, including the availability of ambulance and helicopter services, may improve direct MTC care and result in a decrease in the variation of the undertriage of severely injured patients to MTCs among the Dutch trauma networks. Furthermore, attention needs to be directed to improving primary triage guidelines and instituting uniform interfacility transfer agreements. (C) 2021 Elsevier Ltd. All rights reserved.Trauma Surger

The role of coping strategies in quality of life of adolescents with asthma

This study aimed to determine which coping strategies are associated with better quality of life (QOL) in adolescents with asthma. Furthermore, because coping can mediate the effects of health stressors on QOL, this study also examined the indirect effect of asthma severity on QOL via coping. Between January and May 2003, 553 Dutch adolescents with asthma (aged 12–6 years) completed questionnaires assessing coping strategies, symptom severity, overall QOL and positive QOL domain (positive effects of asthma domain). The relations between symptom severity, coping strategies and QOL were tested with structural equation modelling (SEM). Symptom severity affected overall and positive QOL, both directly and indirectly via coping. The coping strategies restricted lifestyle and worrying about asthma were associated with poorer overall QOL. The use of the coping strategies restricted lifestyle, positive reappraisal, and information seeking was related to increased scores on the positive QOL domain, whereas hiding asthma was related to lower scores on the positive QOL domain