275 research outputs found

    Home Energy Efficiency and Subjective Health in Greater London

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    The UK has introduced legislation that requires net-zero greenhouse gas emissions to be achieved by 2050. Improving the energy efficiency of homes is a key objective to help reach this target, and the UK government's Clean Growth Strategy aims to get many homes up to an Energy Performance Certificate (EPC) Band of C by 2035. The relationship between home energy-efficiency and occupant health and wellbeing remains an area of ongoing research. This paper explores the nexus between home energy efficiency, energy consumption and self-reported health-an indicator of the general health and wellbeing of the population. We focus on Greater London through secondary data analysis. Energy-efficiency ratings and air infiltration rates of dwellings, derived from EPCs, were aggregated and matched to local area self-reported health and energy consumption data obtained from the Greater London Authority's (GLA) Lower Layer Super Output Area (LSOA) Atlas database. Our regression model indicates that improving the energy efficiency (SAP) rating by 10 points for a typical home may reduce household gas consumption by around 7% (95% CIs: 2%, 14%). Beta regression finds a positive, but not statistically significant association between median SAP rating and the proportion of the population reporting 'good or very good' health when considering all Greater London LSOAs (z score = 0.60, p value = 0.55). A statistically significant positive association is observed however when repeating the analysis for the lowest income quartile LSOAs (z score = 2.03, p value = 0.04). This indicates that the least well-off may benefit most from home energy efficiency programs. A statistically significant positive association is also observed for the relationship between self-reported health and air infiltration rates (z score = 2.62, p value = 0.01). The findings support existing evidence for the predominantly naturally ventilated UK housing stock, suggesting that home energy efficiency measures provide a co-benefit for occupant health provided that adequate air exchange is maintained

    Genetic diversity of Brazilian isolates of feline immunodeficiency virus

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    We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

    Modulation of vaccine-induced immune responses to hepatitis C virus in rhesus macaques by altering priming before adenovirus boosting

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    BACKGROUND: Preventive and therapeutic vaccine strategies aimed at controlling hepatitis C virus (HCV) infection should mimic the immune responses observed in patients who control or clear HCV, specifically T helper (Th) type 1 and CD8+ cell responses to multiple antigens, including nonstructural protein (NS) 3. Given the experience with human immunodeficiency virus, the best candidates for this are based on DNA prime, pox, or adenovirus boost regimens. METHODS: In rhesus macaques, we compared NS3-expressing DNA prime and adenovirus boost strategy with 2 alternative priming approaches aimed at modifying Th1 and CD8+ responses: DNA adjuvanted with interleukin (IL)-2- and -12-encoding plasmids or Semliki Forest virus (SFV). RESULTS: All prime-boost regimens elicited NS3-specific B and T cell responses in rhesus macaques, including CD8+ responses. SFV priming induced higher lymphoproliferation and longer Th1 memory responses. The use of IL-2- and IL-12-expressing vectors resulted in reduced Th2 and antibody responses, which led to increased Th1 skewing but not to an increase in the magnitude of the IFN- gamma and CD8+ responses. CONCLUSIONS: All strategies induced Th1 cellular responses to HCV NS3, with fine modulations depending on the different priming approaches. When they are developed for more HCV antigens, these strategies could be beneficial in therapeutic vaccine approaches

    Is It Rational to Assume that Infants Imitate Rationally? A Theoretical Analysis and Critique

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    It has been suggested that preverbal infants evaluate the efficiency of others' actions (by applying a principle of rational action) and that they imitate others' actions rationally. The present contribution presents a conceptual analysis of the claim that preverbal infants imitate rationally. It shows that this ability rests on at least three assumptions: that infants are able to perceive others' action capabilities, that infants reason about and conceptually represent their own bodies, and that infants are able to think counterfactually. It is argued that none of these three abilities is in place during infancy. Furthermore, it is shown that the idea of a principle of rational action suffers from two fallacies. As a consequence, is it suggested that it is not rational to assume that infants imitate rationally. Copyright (C) 2012 S. Karger AG, Base

    The Distances to Open Clusters from Main-Sequence Fitting. III. Improved Accuracy with Empirically Calibrated Isochrones

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    We continue our series of papers on open cluster distances with a critical assessment of the accuracy of main-sequence fitting using isochrones that employ empirical corrections to the color-temperature relations. We use four nearby open clusters with multicolor photometry and accurate metallicities and present a new metallicity for Praesepe ([Fe/H] = +0.11 +/- 0.03) from high-resolution spectra. The internal precision of distance estimates is about a factor of 5 better than the case without the color calibrations. After taking into account all major systematic errors, we obtain distances accurate to about 2%-3% when there exists a good metallicity estimate. Metallicities accurate to better than 0.1 dex may be obtained from BVIcKs photometry alone. We also derive a helium abundance for the Pleiades of Y = 0.279 +/- 0.015, which is equal within the errors to the Sun's initial helium abundance and that of the Hyades. Our best estimates of distances are (m - M)_0 = 6.33 +/- 0.04, 8.03 +/- 0.04, and 9.61 +/- 0.03 to Praesepe, NGC 2516, and M67, respectively. Our Pleiades distance at the spectroscopic metallicity, (m - M)_0 = 5.66 +/- 0.01 (internal) +/- 0.05 (systematic), is in excellent agreement with several geometric distance measurements. We have made calibrated isochrones for -0.3 <= [Fe/H] <= +0.2 available at http://www.astronomy.ohio-state.edu/iso/ .Comment: 28 pages, 23 figures; accepted for publication in the Ap

    Truly reconciled? A dyadic analysis of post-conflict social reintegration in Northern Uganda

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    In the aftermath of civil war or violent internal conflict, one of the key peacebuilding challenges is the reconciliation of former enemies who are members of the same small-scale societies. A failure of social reintegration may contribute to what is known as a conflict trap. To detect lingering hostile attitudes among a community’s various factions is crucial, but the approaches adopted in previous studies tend to focus on the impact of conflict on one or other aggregated indicator of social cohesion rather than on how violence-affected individuals regard and act towards their fellow community members. Here we demonstrate the value of concentrating on this latter dyadic component of social interactions and we use behavioural experiments and a social tie survey to assess, in an appropriately disaggregated manner, social cohesion in a post-conflict setting in northern Uganda. Whereas in self-reported surveys, ex-combatants appear to be well-connected, active members of their communities, the experiments unveil the continued reluctance of other community members to share or cooperate with them; fewer resources are committed to ex-combatants than to others, which is statistically significant. The dyadic nature of our analysis allows us to detect which groups are more prone to discriminate against ex-combatants, which may help facilitate targeted interventions

    T- and B-cell responses to multivalent prime-boost DNA and viral vectored vaccine combinations against hepatitis C virus in non-human primates.

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    Immune responses against multiple epitopes are required for the prevention of hepatitis C virus (HCV) infection, and the progression to phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara (MVA) poxvirus, all expressing hepatitis C virus Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared. All combinations induced specific T-cell immune responses, including high IFN-γ production. The group immunized with the SFV+MVA regimen elicited higher E2-specific responses as compared with the two other modalities, while animals receiving HuAd5 injections elicited lower IL-4 responses as compared with those receiving MVA. The IFN-γ responses to NS3 were remarkably similar between groups. Only the adenovirus induced envelope-specific antibody responses, but these failed to show neutralizing activity. Therefore, the two novel regimens failed to induce superior responses as compared with already existing HCV vaccine candidates. Differences were found in response to envelope proteins, but the relevance of these remain uncertain given the surprisingly poor correlation with immunogenicity data in chimpanzees, underlining the difficulty to predict efficacy from immunology studies.This work was supported by European Union contract QLK2-CT-1999- 00356, by the Biomedical Primate Research Centre, The Netherlands, and by the Swedish Research Council. We are grateful to Alexander van den Berg for technical assistance with the ICS, to our colleagues from Animal Science Department for technical assistance and expert care of the macaques, to the participants of the European HCVacc Cluster who provided help and support, and to Thomas Darton (Oxford Vaccine Group, UK) for input and advice on the manuscript. Christine Rollier is an Oxford Martin fellow and a Jenner Insitute Investigator.This is the author accepted manuscript. The final version is available from Nature Publishing Group at https://doi.org/10.1038/gt.2016.55

    A bacterially-expressed recombinant envelope protein from Usutu virus induces neutralizing antibodies in rabbits

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    Background: Recently, an emerging flavivirus, Usutu virus (USUV), has caused an epidemic among birds in Europe, resulting in a massive die-off in Eurasian blackbirds. Currently found only in Europe and Africa, it can be envisioned that Usutu virus will follow the path of other flaviviruses, like West Nile virus and Zika virus, and will spread via its mosquito vectors and bird hosts to other parts of the world. Several cases of human infections by Usutu virus have already been published. Anticipating this spread, development of an efficacious vaccine would be highly desirable. Method: This study describes the production in E. coli, purification, and refolding of a partial USUV envelope protein. Prior to immunization, the protein was characterized using size exclusion chromatography, transmission electron microscopy and dynamic light scattering, showing the limited presence of virus-like structures, indicating that the protein solution is probably a mixture of mono and multimeric envelope proteins. Results: Immunizations of two rabbits with the refolded E-protein fraction, mixed with a strong adjuvant, resulted in the generation of neutralizing antibodies, as evidenced in an in vitro assay. Discussion: The way forward towards a subunit vaccine against Usutu virus infection is discussed.Microscopic imaging and technolog

    Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway

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    Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with intracellular mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC.  Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed.  Results. Macrophages infected with intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria from infected host cells.  Conclusion. These findings provide a novel mechanistic explanation for mycobacterial intracellular persistence, and suggest that targeting interactions between the mycobacteria and host cell pathways may provide a novel avenue for development of anti-TB therapies
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