978 research outputs found

    The Suzaku view of highly-ionised outflows in AGN: II -- Location, energetics and scalings with Bolometric Luminosity

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    Ongoing studies with XMM-Newton have shown that powerful accretion disc winds, as revealed through highly-ionised Fe\,K-shell absorption at E>=6.7 keV, are present in a significant fraction of Active Galactic Nuclei (AGN) in the local Universe (Tombesi et al. 2010). In Gofford et al. (2013) we analysed a sample of 51 Suzaku-observed AGN and independently detected Fe K absorption in ~40% of the sample, and we measured the properties of the absorbing gas. In this work we build upon these results to consider the properties of the associated wind. On average, the fast winds (v_out>0.01c) are located ~10^{15-18} cm (typically ~10^{2-4} r_s) from their black hole, their mass outflow rates are of the order ~0.01-1 Msun/yr or ~(0.01-1) M_edd and kinetic power is constrained to ~10^{43-45} erg/s, equivalent to ~(0.1-10%) L_edd. We find a fundamental correlation between the source bolometric luminosity and the wind velocity, with v_out \propto L_bol^{\alpha} and \alpha=0.4^{+0.3}_{-0.2}$ (90% confidence), which indicates that more luminous AGN tend to harbour faster Fe K winds. The mass outflow rate M_out, kinetic power L_k and momentum flux P_out of the winds are also consequently correlated with L_bol, such that more massive and more energetic winds are present in more luminous AGN. We investigate these properties in the framework of a continuum-driven wind, showing that the observed relationships are broadly consistent with a wind being accelerated by continuum-scattering. We find that, globally, a significant fraction (~85%) of the sample can plausibly exceed the L_k/L_bol~0.5% threshold thought necessary for feedback, while 45% may also exceed the less conservative ~5% of L_bol threshold as well. This suggests that the winds may be energetically significant for AGN--host-galaxy feedback processes

    Physical Characteristics Explain Ball-Carrying Capability in Sub-Elite Rugby Union Players

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    Purpose: The aims of the present study were two-fold: (i) to investigate the relationship between physical characteristics and the game statistics associated with ball-carrying capability amongst sub-elite rugby union players, and (ii) to predict the level of change in these physical characteristics required to improve the associated game statistic via regression analysis. Methods: Thirty-eight senior professional players (forwards, n = 22; backs, n = 16) were assessed for body mass (BM), back squat (BS) single-repetition maximum (1RM) normalised to BM (1RM/BM), 10 m sprint velocity (S10), 10 m sprint momentum (SM10), and the game statistics from 22 games within the 2019/20 RFU Championship season. The relationship between these measures and the predicted level of change in a physical measure required to improve the total number of the associated game statistic by one were assessed by Pearson’s correlation coefficient and simple regression analyses. Results: In forwards, an ~ 11.5% reduction in BM, an ~ 11.8% improvement in BS 1RM/BM, or an ~ 11.5% increase in S10 was required to improve the game statistics associated with ball-carrying capability. In backs, a ~ 19.3% increase in BM or a ~ 15.6% improvement in SM10 was required. Conclusions: These findings demonstrate that improvements in lower-body relative strength, acceleration performance, and position-specific alterations in body mass are required to maximise the ball-carrying capability and therefore match outcome of sub-elite rugby union players

    Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria.

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    The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms

    Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

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    © 2015 The Authors. Published by Springer Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/srep12955Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ‰7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1 H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a 'healthier' pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.Published versio

    Chinese herbal recipe versus diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial [ISRCTN70292892]

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    BACKGROUND: Duhuo Jisheng Wan (DJW) is perhaps the best known and most widely used Chinese herbal recipe for arthralgia, but the clinical study to verify its efficacy is lacking. The purpose of this study was to compare the efficacy of DJW versus diclofenac in symptomatic treatment of osteoarthritis (OA) of the knee. METHODS: This study was a randomized, double-blind, double-dummy, controlled trial. The 200 patients suffering from OA of the knee, were randomized into the DJW and diclofenac group. The patients were evaluated after a run-in period of one week (week 0) and then weekly during 4 weeks of treatment. The clinical assessments included visual analog scale (VAS) score that assessed pain and stiffness, Lequesne's functional index, time for climbing up 10 steps, as well as physician's and patients' overall opinions on improvement. RESULTS: Ninety four patients in each group completed the study. In the first few weeks of treatment, the mean changes in some variables (VAS, which assessed walking pain, standing pain and stiffness, as well as Lequesne's functional index) of the DJW group were significantly lower than those of the diclofenac group. Afterwards, these mean changes became no different throughout the study. Most of the physician's and patients' overall opinions on improvement at each time point did not significantly differ between the two groups. Approximately 30% of patients in both groups experienced mild adverse events. CONCLUSION: DJW demonstrates clinically comparable efficacy to diclofenac after 4 weeks of treatment. However, the slow onset of action as well as approximately equal rate of adverse events to diclofenac might limit its alternative role in treatment of OA of the knee

    Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

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    Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

    Population-Based Rates of Revision of Primary Total Hip Arthroplasty: A Systematic Review

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    Background: Most research on failure leading to revision total hip arthroplasty (THA) is reported from single centers. We searched PubMed between January 2000 and August 2010 to identify population- or community-based studies evaluating ten-year revision risks. We report ten-year revision risk using the Kaplan-Meier method, stratifying by age and fixation technique. Results: Thirteen papers met the inclusion criteria. Cemented prostheses had Kaplan-Meier estimates of revision-free implant survival of ten years ranging from 88 % to 95%; uncemented prostheses had Kaplan-Meier estimates from 80 % to 85%. Estimates ranged from 72 % to 86 % in patients less than 60 years old and from 90 to 96 % in older patients. Conclusion: Data reported from national registries suggest revision risks of 5 to 20 % ten years following primary THA. Revision risks are lower in older THA recipients. Uncemented implants may have higher ten-year rates of revision, regardless of age

    Xenopus as a Model System for the Study of GOLPH2/GP73 Function: Xenopus golph2 Is Required for Pronephros Development

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    GOLPH2 is a highly conserved protein. It is upregulated in a number of tumors and is being considered as an emerging biomarker for related diseases. However, the function of GOLPH2 remains unknown. The Xenopus model is used to study the function of human proteins. We describe the isolation and characterization of Xenopus golph2, which dimerizes and localizes to the Golgi in a manner similar to human GOLPH2. Xenopus golph2 is expressed in the pronephros during early development. The morpholino-mediated knockdown of golph2 results in edema formation. Additionally, Nephrin expression is enhanced in the glomus, and the expression of pronephric marker genes, such as atp1b1, ClC-K, NKCC2, and NBC1, is diminished in the tubules and duct. Expression patterns of the transcription factors WT1, Pax2, Pax8, Lim1, GATA3, and HNF1β are also examined in the golph2 knockdown embryos, the expression of WT1 is increased in the glomus and expanded laterally in the pronephric region. We conclude that the deletion of golph2 causes an increase in the expression of WT1, which may promote glomus formation and inhibit pronephric tubule differentiation
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