136 research outputs found

    Co-designing the next generation of home energy management systems with lead-users

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    Home energy management systems are widely promoted as essential components of future low carbon economies. It is argued in this paper that assumptions surrounding their deployment, and the methods used to design them, emerge from discredited models of people and energy. This offers an explanation for why their field trial performance is so inconsistent. A first of a kind field trial is reported. Three eco communities took part in a comprehensive participatory design exercise as lead users. The challenge was to help users synchronise their energy use behaviours with the availability of locally generated renewable energy sources. To meet this aim, a set of highly novel Home Energy Management interfaces were co-designed and tested. Not only were the designs radically different to the norm, but they also yielded sustained user engagement over a six-month follow-up period. It is argued that user-centred design holds the key to unlocking the energy saving potential of new domestic technologies, and this study represents a bold step in that direction

    Reconstructing transmission trees for communicable diseases using densely sampled genetic data.

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    Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation.Funding received from the following: The European Community [Mastering Hospital Antimicrobial Resistance (MOSAR) network contract LSHP-CT-2007-037941]. The National Institute of General Medical Sciences of the National Institutes of Health under award number U54GM088558. The UK Medical Research Council (Unit Programme number U105260566). The UKCRC Translational Infection Research Initiative (MRC Grant number G1000803) and Public Health England. The Medical Research Council and Department for International Development (Grant number MR/K006924/1). The Mahidol Oxford Tropical Medicine Research Unit is part of the Wellcome Trust Major Overseas Programme in SE Asia (Grant number 106698/Z/14/Z).This is the final version of the article. It first appeared from the Institute of Mathematical Statistics via http://dx.doi.org/10.1214/15-AOAS89

    Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.

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    OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children. STUDY DESIGN: Observational cohort study of children with SAB. SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK. PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012. METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group. RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4 years (IQR 0.2-10.7 years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90 days following onset of SAB. CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.This work was supported by grants from the UK Clinical Research Collaboration (UKCRC) Translational Infection Research Initiative (TIRI); the Medical Research Council (G1000803), with contributions from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research (NIHR) on behalf of the UK Department of Health, and the Chief Scientist of the Scottish Government Health Directorate; the Public Health England; and the NIHR Cambridge Biomedical Research Centre

    Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

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    IMPORTANCE: Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. OBJECTIVE: Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. MATERIALS AND METHODS: The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. RESULTS: After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). CONCLUSIONS: Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities

    Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland.

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    The correct interpretation of microbial sequencing data applied to surveillance and outbreak investigation depends on accessible genomic databases to provide vital genetic context. Our aim was to construct and describe a United Kingdom MRSA database containing over 1000 methicillin-resistant Staphylococcus aureus (MRSA) genomes drawn from England, Northern Ireland, Wales, Scotland, and the Republic of Ireland over a decade. We sequenced 1013 MRSA submitted to the British Society for Antimicrobial Chemotherapy by 46 laboratories between 2001 and 2010. Each isolate was assigned to a regional healthcare referral network in England and was otherwise grouped based on country of origin. Phylogenetic reconstructions were used to contextualize MRSA outbreak investigations and to detect the spread of resistance. The majority of isolates (n = 783, 77%) belonged to CC22, which contains the dominant United Kingdom epidemic clone (EMRSA-15). There was marked geographic structuring of EMRSA-15, consistent with widespread dissemination prior to the sampling decade followed by local diversification. The addition of MRSA genomes from two outbreaks and one pseudo-outbreak demonstrated the certainty with which outbreaks could be confirmed or refuted. We identified local and regional differences in antibiotic resistance profiles, with examples of local expansion, as well as widespread circulation of mobile genetic elements across the bacterial population. We have generated a resource for the future surveillance and outbreak investigation of MRSA in the United Kingdom and Ireland and have shown the value of this during outbreak investigation and tracking of antimicrobial resistance.We are grateful for assistance from the library construction, sequencing and core informatics teams at the Wellcome Trust Sanger Institute. We acknowledge David Harris and Martin Aslett for their help in submitting the sequenced isolates to public databases. The study was supported by grants from the UKCRC Translational Infection Research Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); by Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute; and by a Healthcare Infection Society Major Reasearch Grant. MET is a Clinician Scientist Fellow, supported by the Academy of Medical Sciences and the Health Foundation and the NIHR Cambridge Biomedical Research Centre. BGS was supported by Wellcome Trust grant number 089472. The study was approved by the University of Cambridge Human Biology Research Ethics Committee (reference HBREC.2013.05), and by the Cambridge University Hospitals NHS Foundation Trust Research and Development Department (reference A092869). Isolates were supplied by the BSAC Resistance Surveillance Project.This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gr.196709.11

    BLAST: Correlations in the Cosmic Far-Infrared Background at 250, 350, and 500 microns Reveal Clustering of Star-Forming Galaxies

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    We detect correlations in the cosmic far-infrared background due to the clustering of star-forming galaxies in observations made with the Balloon-borne Large Aperture Submillimeter Telescope, BLAST, at 250, 350, and 500 microns. We perform jackknife and other tests to confirm the reality of the signal. The measured correlations are well fit by a power law over scales of 5-25 arcminutes, with Delta I/I = 15.1 +/- 1.7%. We adopt a specific model for submillimeter sources in which the contribution to clustering comes from sources in the redshift ranges 1.3 <= z <= 2.2, 1.5 <= z <= 2.7, and 1.7 <= z <= 3.2, at 250, 350, and 500 microns, respectively. With these distributions, our measurement of the power spectrum, P(k_theta), corresponds to linear bias parameters, b = 3.8 +/- 0.6, 3.9 +/- 0.6 and 4.4 +/- 0.7, respectively. We further interpret the results in terms of the halo model, and find that at the smaller scales, the simplest halo model fails to fit our results. One way to improve the fit is to increase the radius at which dark matter halos are artificially truncated in the model, which is equivalent to having some star-forming galaxies at z >= 1 located in the outskirts of groups and clusters. In the context of this model we find a minimum halo mass required to host a galaxy is log (M_min / M_sun) = 11.5 (+0.4/-0.1), and we derive effective biases $b_eff = 2.2 +/- 0.2, 2.4 +/- 0.2, and 2.6 +/- 0.2, and effective masses log (M_eff / M_sun) = 12.9 +/- 0.3, 12.8 +/- 0.2, and 12.7 +/- 0.2, at 250, 350, and 500 microns, corresponding to spatial correlation lengths of r_0 = 4.9, 5.0, and 5.2 +/- 0.7 h^-1 Mpc, respectively. Finally, we discuss implications for clustering measurement strategies with Herschel and Planck.Comment: Accepted for publication in the Astrophysical Journal. Maps and other results available at http://blastexperiment.info

    Burkholderia pseudomallei Is Genetically Diverse in Agricultural Land in Northeast Thailand

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    Burkholderia pseudomallei is the cause of melioidosis, a serious human infection most commonly diagnosed in southeast Asia and northern Australia. The organism lives in the soil in a specific geographical distribution and infection results from bacterial inoculation, inhalation or ingestion. The purpose of this study was to define the distribution and genetic diversity of B. pseudomallei in agricultural land where most human infections probably occur. We performed soil sampling and culture for the presence of B. pseudomallei in 100 equally spaced points within a rice paddy in northeast Thailand, and undertook genotyping of primary culture plate colonies from 11 sampling points. We identified 7 different genotypes, with relatively limited overlap between different sampling points. Two samples contained more than one B. pseudomallei genotype, in which a numerically dominant genotype coexisted with one or more additional genotypes present as a minority population. We conclude that genetic diversity and structuring of B. pseudomallei exists despite the effects of flooding and the physical and chemical processes associated with farming. These findings inform future efforts to define B. pseudomallei in the environment, and should be considered during the design stage of studies comparing B. pseudomallei isolated from the environment and from patients with invasive disease

    NLRC4 and TLR5 Each Contribute to Host Defense in Respiratory Melioidosis

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    Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for melioidosis. As a flagellated bacterium encoding type III secretion systems, B. pseudomallei may trigger numerous host pathogen recognition receptors. TLR5 is a flagellin sensor located on the plasma membrane. NLRC4, along with NAIP proteins, assembles a canonical caspase-1-dependent inflammasome in the cytoplasm that responds to flagellin (in mice) and type III secretion system components (in mice and humans). In a murine model of respiratory melioidosis, Tlr5 and Nlrc4 each contributed to survival. Mice deficient in both Tlr5 and Nlrc4 were not more susceptible than single knockout animals. Deficiency of Casp1/Casp11 resulted in impaired bacterial control in the lung and spleen; in the lung much of this effect was attributable to Nlrc4, despite relative preservation of pulmonary IL-1ÎČ production in Nlrc4−/− mice. Histologically, deficiency of Casp1/Casp11 imparted more severe pulmonary inflammation than deficiency of Nlrc4. The human NLRC4 region polymorphism rs6757121 was associated with survival in melioidosis patients with pulmonary involvement. Co-inheritance of rs6757121 and a functional TLR5 polymorphism had an additive effect on survival. Our results show that NLRC4 and TLR5, key components of two flagellin sensing pathways, each contribute to host defense in respiratory melioidosis

    A measurement of the millimetre emission and the Sunyaev-Zel'dovich effect associated with low-frequency radio sources

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    We present a statistical analysis of the millimetre-wavelength properties of 1.4GHz-selected sources and a detection of the Sunyaev–Zel’dovich (SZ) effect associated with the haloes that host them. We stack data at 148, 218 and 277GHz from the Atacama Cosmology Telescope at the positions of a large sample of radio AGN selected at 1.4GHz. The thermal SZ effect associated with the haloes that host the AGN is detected at the 5σ level through its spectral signature, representing a statistical detection of the SZ effect in some of the lowest mass haloes (average M 200 ≈ 10 13 M. h −1 70 ) studied to date. The relation between the SZ effect and mass (based on weak lensing measurements of radio galaxies) is consistent with that measured by Planck for local bright galaxies. In the context of galaxy evolution models, this study confirms that galaxies with radio AGN also typically support hot gaseous haloes. Adding Herschel observations allows us to show that the SZ signal is not significantly contaminated by dust emission. Finally, we analyse the contribution of radio sources to the angular power spectrum of the cosmic microwave background
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