502 research outputs found
Agencies, ministers and civil servants in Britain
Huge variations exist in the relationships between politicians and agenciesin Britain, from very frequent contact in a politicised atmosphere to thecomplete absence of a direct relationship at all. The nature of therelationship appears to be determined less by agency status as such as bythe political sensitivity of particular policy issues. While politicians are notinvolved in the day-to-day running of most agencies, they have beenconcerned with operational matters in a small number of agencies. Whilemany agencies have no direct input into policy issues (and there are fewdirectly concerning them), in a limited number of cases the agency is themain source of policy advice because it is the repository of expertise, andin others the agency has the right to be consulted about any policyproposals affecting them, and to make policy proposals. The British NextSteps agency form, because of it relatively informal status, is relativelyadaptable to new purposes. Thus, agency status as such has provided littlehindrance to the new Labour government. Similarly, while agencies wereoriginally set up and largely operate with a vertical perspective on meetingtheir own targets, the form is adaptable to cross-organisational targets,though it cannot solve conflicting objectives or policies
Experimental pig-to-pig transmission dynamics for African swine fever virus, Georgia 2007/1 strain
African swine fever virus (ASFV) continues to cause outbreaks in domestic pigs and wild boar in Eastern European countries. To gain insights into its transmission dynamics, we estimated the pig-to-pig basic reproduction number (R 0) for the Georgia 2007/1 ASFV strain using a stochastic susceptible-exposed-infectious-recovered (SEIR) model with parameters estimated from transmission experiments. Models showed that R 0 is 2·8 [95% confidence interval (CI) 1·3–4·8] within a pen and 1·4 (95% CI 0·6–2·4) between pens. The results furthermore suggest that ASFV genome detection in oronasal samples is an effective diagnostic tool for early detection of infection. This study provides quantitative information on transmission parameters for ASFV in domestic pigs, which are required to more effectively assess the potential impact of strategies for the control of between-farm epidemic spread in European countries.ISSN:0950-2688ISSN:1469-440
System Identification Methods for Aeroelastic Rotor Models. G.U. Aero Report 9507
No abstract available
Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis.
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis
Evaluating anemometer drift: A statistical approach to correct biases in wind speed measurement
Recent studies on observed wind variability have revealed a decline (termed “stilling”) of near-surface wind speed during the last 30–50 years over many mid-latitude terrestrial regions, particularly in the Northern Hemisphere. The well-known impact of cup anemometer drift (i.e., wear on the bearings) on the observed weakening of wind speed has been mentioned as a potential contributor to the declining trend. However, to date, no research has quantified its contribution to stilling based on measurements, which is most likely due to lack of quantification of the ageing effect. In this study, a 3-year field experiment (2014–2016) with 10-minute paired wind speed measurements from one new and one malfunctioned (i.e., old bearings) SEAC SV5 cup anemometer which has been used by the Spanish Meteorological Agency in automatic weather stations since mid-1980s, was developed for assessing for the first time the role of anemometer drift on wind speed measurement. The results showed a statistical significant impact of anemometer drift on wind speed measurements, with the old anemometer measuring lower wind speeds than the new one. Biases show a marked temporal pattern and clear dependency on wind speed, with both weak and strong winds causing significant biases. This pioneering quantification of biases has allowed us to define two regression models that correct up to 37% of the artificial bias in wind speed due to measurement with an old anemometer
Seizure first aid training for people with Epilepsy (SAFE) frequently attending emergency departments and their significant others : results of a UK multi-centre randomised controlled pilot trial
Objective To determine the feasibility and optimal design of a randomised controlled trial (RCT) of Seizure First Aid Training For Epilepsy (SAFE).
Design Pilot RCT with embedded microcosting.
Setting Three English hospital emergency departments (EDs).
Participants Patients aged ≥16 with established epilepsy reporting ≥2 ED visits in the prior 12 months and their significant others (SOs).
Interventions Patients (and their SOs) were randomly allocated (1:1) to SAFE plus treatment-as-usual (TAU) or TAU alone. SAFE is a 4-hour group course.
Main outcome measures Two criteria evaluated a definitive RCT’s feasibility: (1) ≥20% of eligible patients needed to be consented into the pilot trial; (2) routine data on use of ED over the 12 months postrandomisation needed securing for ≥75%. Other measures included eligibility, ease of obtaining routine data, availability of self-report ED data and comparability, SAFE’s effect and intervention cost.
Results Of ED attendees with a suspected seizure, 424 (10.6%) patients were eligible; 53 (12.5%) patients and 38 SOs consented. Fifty-one patients (and 37 SOs) were randomised. Routine data on ED use at 12 months were secured for 94.1% patients. Self-report ED data were available for 66.7% patients. Patients reported more visits compared with routine data. Most (76.9%) patients randomised to SAFE received it and no related serious adverse events occurred. ED use at 12 months was lower in the SAFE+TAU arm compared with TAU alone, but not significantly (rate ratio=0.62, 95% CI 0.33 to 1.17). A definitive trial would need ~674 patient participants and ~39 recruitment sites. Obtaining routine data was challenging, taking ~8.5 months.
Conclusions In satisfying only one predetermined ‘stop/go’ criterion, a definitive RCT is not feasible. The low consent rate in the pilot trial raises concerns about a definitive trial’s finding’s external validity and means it would be expensive to conduct. Research is required into how to optimise recruitment from the target population
The serum proteome of Atlantic salmon, Salmo salar, during pancreas disease (PD) following infection with salmonid alphavirus subtype 3 (SAV3)
Salmonid alphavirus is the aetological agent of pancreas disease (PD) in marine Atlantic salmon, Salmo salar, and rainbow trout, Oncorhynchus mykiss, with most outbreaks in Norway caused by SAV subtype 3 (SAV3). This atypical alphavirus is transmitted horizontally causing a significant economic impact on the aquaculture industry. This histopathological and proteomic study, using an established cohabitational experimental model, investigated the correlation between tissue damage during PD and a number of serum proteins associated with these pathologies in Atlantic salmon. The proteins were identified by two-dimensional electrophoresis, trypsin digest and peptide MS/MS fingerprinting. A number of humoral components of immunity which may act as biomarkers of the disease were also identified. For example, creatine kinase, enolase and malate dehydrogenase serum concentrations were shown to correlate with pathology during PD. In contrast, hemopexin, transferrin, and apolipoprotein, amongst others, altered during later stages of the disease and did not correlate with tissue pathologies. This approach has given new insight into not only PD but also fish disease as a whole, by characterisation of the protein response to infection, through pathological processes to tissue recovery.
Biological significance:
Salmonid alphavirus causes pancreas disease (PD) in Atlantic salmon, Salmo salar, and has a major economic impact on the aquaculture industry. A proteomic investigation of the change to the serum proteome during PD has been made with an established experimental model of the disease. Serum proteins were identified by two-dimensional electrophoresis, trypsin digest and peptide MS/MS fingerprinting with 72 protein spots being shown to alter significantly over the 12 week period of the infection. The concentrations of certain proteins in serum such as creatine kinase, enolase and malate dehydrogenase were shown to correlate with tissue pathology while other proteins such as hemopexin, transferrin, and apolipoprotein, altered in concentration during later stages of the disease and did not correlate with tissue pathologies. The protein response to infection may be used to monitor disease progression and enhance understanding of the pathology of PD
Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC
Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo
Cloud Cover in the Australian Region: Development and Validation of a Cloud Masking, Classification and Optical Depth Retrieval Algorithm for the Advanced Himawari Imager
This paper presents a cloud masking, cloud classification and optical depth retrieval algorithm and its application to the Advanced Himawari Imager (AHI) on the Himawari-8/9 satellites using visible, near infrared and thermal infrared bands. A time-series-based approach was developed for cloud masking which was visually assessed and quantitatively validated over 1 year of daytime data for both land and ocean against the level 2 Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) 1 km cloud layer product (version 4.10). An overall hit rate (the proportion of pixels identified by both sensors as either clear or cloudy) of 87% was found. However, analysis revealed that, when partially cloudy conditions were experienced, the small footprint of the CALIOP sensor (70 meters beam size sampling every 330 meters along the ground track) had a major impact on the hit rate. When partially cloudy pixels are excluded a hit rate of ~98% was found, even for thin clouds with optical depth less than 0.25. A two-way confidence index for the cloud mask was developed which could be used to reclassify the pixels depending on applications, either biasing toward clearness or cloudiness. On the basis of the cloud masking, classification and optical depth retrieval was performed based on radiative transfer modeling. Small modeling error was found, and inspection of typical cloud classification examples showed that the results were consistent with cloud texture and cloud top temperatures. While difficult to validate retrieved cloud properties directly, an indirect quantitative validation was performed by comparing surface-level solar flux computed from the retrieved cloud properties with in-situ measurements at 11 sites across Australia for up to 3 years. Excellent agreement between calculated and measured solar flux was found, with a mean monthly bias of 2.96 W/m2 and RMSE of 8.91 W/m2, and the correlation coefficient exceeding 0.98 at all sites. Further assessment was conducted by comparing seasonal and annual cloud fraction with that of ISCCP (International Satellite Cloud Climatology Project) over Australia and surrounding region. It showed high degree of resemblance between the two datasets in their total cloud fraction. The geographical distribution of cloud classes also showed broad resemblance, though detailed differences exist, especially for high clouds, which is probably due to the use of different cloud classification systems in the two datasets. The products generated from this study are being used in several applications including ocean color remote sensing, solar energy, vegetation monitoring and detection of smoke for the study of their health impacts, and aerosol and land surface bidirectional reflectance distribution function (BRDF) retrieval. The method developed herein can be applied to other geostationary sensors
Materialising architecture for social care: brick walls and compromises in design for later life.
This article reports on an ethnography of architectural projects for later life social care in the UK. Informed by recent debates in material studies and ‘materialities of care’ we offer an analysis of a care home project that is sensitive to architectural materials that are not normally associated with care and wellbeing. Although the care home design project we focus on in this article was never built, we found that design discussions relating to both a curved brick wall and bricks more generally were significant to its architectural ‘making’. The curved wall and the bricks were used by the architects to encode quality and values of care into their design. This was explicit in the design narrative that was core to a successful tender submitted by a consortium comprising architects, developers, contractors, and a care provider to a local authority who commissioned the care home. However, as the project developed, initial consensus for the design features fractured. Using a materialised analysis, we document the tussles generated by the curved wall and the bricks and argue that mundane building materials can be important to, and yet marginalised within, the relations inherent within an ‘architectural care assemblage.’ During the design process we saw how decisions about materials are contentious and they act as a catalyst of negotiations that compromise ‘materialities of care.
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