The local dimension of energy

In this paper, we postulate that some of the best opportunities for reducing energy demand and carbon emissions are through stronger involvement and leadership from local government. We show that local government can and do have a significant impact on both energy production and energy consumption and are important participants for the implementation of distributed generation (DG). the progress being made by successful local governments can be narrowed to three key factors. First, they have all recognised the co-benefits of a local energy strategy: a reduction in fuel poverty, increased employment, improved quality of life and mitigation of uncertain fuel supplies and prices. Secondly, successful councils have strong political leadership and employee support to implement the structural change to bring about change. Thirdly, leading councils have gained momentum by working in partnership with utilities, private companies, NGO’s, DNO’s and government departments to raise finance and garner support. While climate change remains a global issue, some of the best strategies for mitigation are implemented at the local level

The application of plastic compression to modulate fibrin hydrogel mechanical properties.

The inherent biocompatibility of fibrin hydrogels makes them an attractive material for use in a wide range of tissue engineering applications. Despite this, their relatively low stiffness and high compliance limits their potential for certain orthopaedic applications. Enhanced mechanical properties are desirable so as to withstand surgical handling and in vivo loading after implantation and additionally, can provide important cues to cells seeded within the hydrogel. Standard methods used to enhance the mechanical properties of biological scaffolds such as chemical or thermal crosslinking cannot be used with fibrin hydrogels as cell seeding and gel formation occurs simultaneously. The objective of this study was to investigate the use of plastic compression as a means to improve the mechanical properties of chondrocyte-seeded fibrin hydrogels and to determine the influence of such compression on cell viability within these constructs. It was found that the application of 80% strain to fibrin hydrogels for 30 min (which resulted in a permanent strain of 47.4%) produced a 2.1-fold increase in the subsequent compressive modulus. Additionally, chondrocyte viability was maintained in the plastically compressed gels with significant cellular proliferation and extracellular matrix accumulation observed over 28 days of culture. In conclusion, plastic compression can be used to modulate the density and mechanical properties of cell-seeded fibrin hydrogels and represents a useful tool for both in theatre and in vitro tissue engineering applications

The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study [version 1; peer review: 2 approved]

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. / Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). / Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to -0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p<0.0001). Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. / Conclusion: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Cross-cultural generalizability of suicide first aid actions: an analysis of agreement across expert consensus studies from a range of countries and cultures

Background A number of Delphi expert consensus studies have been carried out with different countries and cultural groups to develop guidelines on how a member of the public should provide assistance to a person who is suicidal. The present study aimed to determine whether cross-culturally generalizable suicide first aid actions are possible by comparing agreement across these Delphi studies. Methods Data on endorsement rates for items were compared across six Delphi studies. These studies involved panels of professionals and consumer advocates from English-speaking countries, professionals from Sri Lanka, professionals from Japan, professionals from India, professionals from the Philippines, and professionals and consumer advocates in refugee and immigrant mental health. Correlations were calculated between item endorsement rates across panels. Results There were 18 items that were highly endorsed across all eight of the Delphi panels and an additional 15 items highly endorsed across the panels from the three lower middle-income countries (India, Philippines and Sri Lanka). Correlations across panels in item endorsement rates were all 0.60 or above, but were higher between panels from countries that are socioeconomically similar. Conclusions There is broad agreement across the diverse expert panels about what are appropriate suicide first aid actions for members of the public, indicating that cross-cultural generalizability is possible. However, there is also some cultural specificity, indicating the need for local tailoring

Outcomes of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical Characterization Protocol (UK): a prospective observational study

BACKGROUND: Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19

Assessment of ecological status in UK lakes using benthic diatoms

The European Union’s Water Framework Directive (WFD) requires that all water bodies in Europe achieve good ecological status (GES) by 2015. We developed an ecological classification tool for UK lakes based on benthic diatoms, a key component of the biological-quality element macrophytes and phytobenthos. A database of 1079 epilithic and epiphytic diatom samples and matching environmental data was assembled from 228 UK lakes. The data set was divided into 3 lake types: low, medium, and high alkalinity. A lake trophic diatom index (LTDI) was developed based on modification of the trophic diatom index (TDI) for rivers, and ecological quality ratios (EQRs) were generated for each lake type. The high/good status boundary was defined as the 25th percentile of EQRs of all reference sites (identified based on independent sedimentary-diatom-assemblage data or catchment point-source and landuse data), whereas the good/moderate boundary was set at the point at which nutrient-sensitive and nutrient-tolerant taxa were present in equal relative abundance. The moderate/poor and poor/bad boundaries were defined by equal division of the remaining EQR gradient. Samples from reference sites were used to predict the expected LTDI value for each sample, and these values were compared with the classifications derived from the LTDI. For lakes identified as reference sites, 68% were classified as having high status and 32% as having good. The model predicted 81% of nonreference lakes to have good or worse status. The model was applied to 17 English lakes (10 low- and 7 medium-alkalinity) for which classification based on other WFD tools was available. The classifications based on LTDI gave the same status (within 1 class) as other biological elements for 11 of the 17 lakes (65%). Thus, the LTDI gives a reliable assessment of the condition of the littoral biofilm and is a key component of a WFD-compliant tool kit for classifying UK standing waters

New constraints on the free-streaming of warm dark matter from intermediate and small scale Lyman-α forest data

We present new measurements of the free-streaming of warm dark matter (WDM) from Lyman-α flux-power spectra. We use data from the medium resolution, intermediate redshift XQ-100 sample observed with the X-shooter spectrograph (z=3–4.2) and the high-resolution, high-redshift sample used in Viel et al. (2013) obtained with the HIRES/MIKE spectrographs (z=4.2 – 5.4 ). Based on further improved modelling of the dependence of the Lyman- α flux-power spectrum on the free-streaming of dark matter, cosmological parameters, as well as the thermal history of the intergalactic medium (IGM) with hydrodynamical simulations, we obtain the following limits, expressed as the equivalent mass of thermal relic WDM particles. The XQ-100 flux power spectrum alone gives a lower limit of 1.4 keV, the re-analysis of the HIRES/MIKE sample gives 4.1 keV while the combined analysis gives our best and significantly strengthened lower limit of 5.3 keV (all 2 σ C.L.). The further improvement in the joint analysis is partly due to the fact that the two data sets have different degeneracies between astrophysical and cosmological parameters that are broken when the data sets are combined, and more importantly on chosen priors on the thermal evolution. These results all assume that the temperature evolution of the IGM can be modeled as a power law in redshift. Allowing for a nonsmooth evolution of the temperature of the IGM with sudden temperature changes of up to 5000 K reduces the lower limit for the combined analysis to 3.5 keV. A WDM with smaller thermal relic masses would require, however, a sudden temperature jump of 5000 K or more in the narrow redshift interval z = 4.6 – 4.8 , in disagreement with observations of the thermal history based on high-resolution resolution Lyman- α forest data and expectations for photo-heating and cooling in the low density IGM at these redshifts.V. I. is supported by U.S. NSF Grant No. AST-1514734. V. I. also thanks M. McQuinn for useful discussions, and IAS, Princeton, for hospitality during his stay where part of this work was completed. M. V. and T. S. K. are supported by ERC-StG “cosmoIGM”. S. L. has been supported by FONDECYT grant number 1140838 and partially by PFB-06 CATA. V. D., M. V., S. C. acknowledge support from the PRIN INAF 2012 “The X-Shooter sample of 100 quasar spectra at z ∼ 3.5 : Digging into cosmology and galaxy evolution with quasar absorption lines. G. B. is supported by the NSF under award AST-1615814. S. L. E. acknowledges the receipt of an NSERC Discovery Grant. M. H. acknowledges support by ERC ADVANCED GRANT 320596 “The Emergence of Structure during the epoch of Reionization”. L. C. is supported by YDUN DFF 4090-00079. K. D. D. is supported by an NSF AAPF fellowship awarded under NSF grant AST-1302093. J. S. B. acknowledges the support of a Royal Society University Research Fellowship. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 189.A-0424. This work made use of the DiRAC High Performance Computing System (HPCS) and the COSMOS shared memory service at the University of Cambridge. These are operated on behalf of the STFC DiRAC HPC facility. This equipment is funded by BIS National E-infrastructure capital grant ST/J005673/1 and STFC grants ST/H008586/1, ST/K00333X/1

Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis