4,739 research outputs found

    Owner perceptions of their cat's quality of life when treated with a modified University of Wisconsin-Madison protocol for lymphoma

    Get PDF
    The objectives of this study were to assess owner perceptions of their cat’s quality of life during treatment for lymphoma with a doxorubicin-containing multi-agent chemotherapy protocol, whether various health-related parameters correlated with quality of life scores, and to assess owner satisfaction with the protocol

    Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

    Get PDF
    Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

    Determining the clog state of constructed wetlands using an embeddable Earth's Field Nuclear Magnetic Resonance probe

    Get PDF
    The recent rise in interest of green technologies has led to significant adoption of the constructed wetland as a waste water treatment technique. This increased popularity has only been mired by the decline in operational lifetime of wetland units, leading to the need for more regular, time consuming, and expensive rejuvenation techniques to be performed than initially anticipated. To extend operational lifetimes and increase efficiency of wetland units, it is crucial to have an accurate method to determine the internal state of the wetland system. The most important parameter to measure within the reed bed is the clog state of the system, which is representative of the overall system health. In previous work, magnetic resonance (MR) measurements, parameters of T1 and T2eff, have been demonstrated as extremely powerful tools to determine the internal clog state of a wetland [1, 2]. Measurements have been performed in a laboratory setting, using low field permanent magnet arrangements. This work presents an Earth's Field Nuclear Magnetic Resonance (EFNMR) probe suitable for in situ measurements within constructed wetlands. We show T2eff and T1 measurements using the EFNMR probe. T1 values are shown to be sensitive to the change in the clog state with 1498 ms for the thickly clogged sample and 2728 ms for the thinly clogged sample. T2eff values are shown to be marginally more sensitive to clog state with 630 ms for a thickly clogged sample and 1212 ms for the thinly clogged sample. This gives distinguishable variation within both parameters suggesting that this probe is suitable for embedding into an operational constructed wetland. This work was conducted as part of an EU FP7 project to construct an Automated Reed Bed Installation, "ARBI"

    P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

    Get PDF
    Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

    The inevitable youthfulness of known high-redshift radio galaxies

    Full text link
    Radio galaxies can be seen out to very high redshifts, where in principle they can serve as probes of the early evolution of the Universe. Here we show that for any model of radio-galaxy evolution in which the luminosity decreases with time after an initial rapid increase (that is, essentially all reasonable models), all observable high-redshift radio-galaxies must be seen when the lobes are less than 10^7 years old. This means that high-redshift radio galaxies can be used as a high-time-resolution probe of evolution in the early Universe. Moreover, this result helps to explain many observed trends of radio-galaxy properties with redshift [(i) the `alignment effect' of optical emission along radio-jet axes, (ii) the increased distortion in radio structure, (iii) the decrease in physical sizes, (iv) the increase in radio depolarisation, and (v) the increase in dust emission] without needing to invoke explanations based on cosmology or strong evolution of the surrounding intergalactic medium with cosmic time, thereby avoiding conflict with current theories of structure formation.Comment: To appear in Nature. 4 pages, 2 colour figures available on request. Also available at http://www-astro.physics.ox.ac.uk/~km

    Modelling the long-term carbon cycle, atmospheric CO2, and Earth surface temperature from late Neoproterozoic to present day

    Get PDF
    Over geological timescales, CO2 levels are determined by the operation of the long term carbon cycle, and it is generally thought that changes in atmospheric CO2 concentration have controlled variations in Earth's surface temperature over the Phanerozoic Eon. Here we compile independent estimates for global average surface temperature and atmospheric CO2 concentration, and compare these to the predictions of box models of the long term carbon cycle COPSE and GEOCARBSULF. We find a strong relationship between CO2 forcing and temperature from the proxy data, for times where data is available, and we find that current published models reproduce many aspects of CO2 change, but compare poorly to temperature estimates. Models are then modified in line with recent advances in understanding the tectonic controls on carbon cycle source and sink processes, with these changes constrained by modelling 87Sr/86Sr ratios. We estimate CO2 degassing rates from the lengths of subduction zones and rifts, add differential effects of erosion rates on the weathering of silicates and carbonates, and revise the relationship between global average temperature changes and the temperature change in key weathering zones. Under these modifications, models produce combined records of CO2 and temperature change that are reasonably in line with geological and geochemical proxies (e.g. central model predictions are within the proxy windows for >~75% of the time covered by data). However, whilst broad long-term changes are reconstructed, the models still do not adequately predict the timing of glacial periods. We show that the 87Sr/86Sr record is largely influenced by the weathering contributions of different lithologies, and is strongly controlled by erosion rates, rather than being a good indicator of overall silicate chemical weathering rates. We also confirm that a combination of increasing erosion rates and decreasing degassing rates over the Neogene can cause the observed cooling and Sr isotope changes without requiring an overall increase in silicate weathering rates. On the question of a source or sink dominated carbon cycle, we find that neither alone can adequately reconstruct the combination of CO2, temperature and strontium isotope dynamics over Phanerozoic time, necessitating a combination of changes to sources and sinks. Further progress in this field relies on >108 year dynamic spatial reconstructions of ancient tectonics, paleogeography and hydrology. Whilst this is a significant challenge, the latest reconstruction techniques, proxy records and modelling advances make this an achievable target

    Escherichia coli induces apoptosis and proliferation of mammary cells

    Get PDF
    Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation
    corecore