125 research outputs found

    Analysing the Transverse Structure of the Relativistic Jets of AGN

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    This paper describes a method of fitting total intensity and polarization profiles in VLBI images of astrophysical jets to profiles predicted by a theoretical model. As an example, the method is used to fit profiles of the jet in the Active Galactic Nucleus Mrk501 with profiles predicted by a model in which a cylindrical jet of synchrotron plasma is threaded by a magnetic field with helical and disordered components. This fitting yields model Stokes Q profiles that agree with the observed profiles to within the 1-2 \sigma uncertainties; the I model and observed profiles are overall not in such good agreement, with the model I profiles being generally more symmetrical than the observed profiles. Consistent fitting results are obtained for profiles derived from 6cm VLBI images at two distances from the core, and also for profiles obtained for different wavelengths at a single location in the VLBI jet. The most striking success of the model is its ability to reproduce the spine-sheath polarization structure observed across the jet. Using the derived viewing angle in the jet rest frame, \delta' approximately 83 degrees, together with a superluminal speed reported in the literature, \beta apparent = 3.3, yields a solution for the viewing angle and velocity of the jet in the observer's frame \delta degrees and \beta approximately 0.96. Although these results for Mrk501 must be considered tentative, the combined analysis of polarization profiles and apparent component speeds holds promise as a means of further elucidating the magnetic field structures and other parameters of parsec-scale AGN jets

    Equipoise across the patient population: Optimising recruitment to a randomised controlled trial

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    © 2016 The Author(s). Background: This paper proposes a novel perspective on the value of qualitative research for improving trial design and optimising recruitment. We report findings from a qualitative study set within the OPEN trial, a surgical randomised controlled trial (RCT) comparing two interventions for recurrent bulbar urethral stricture, a common cause of urinary problems in men. Methods: Interviews were conducted with men meeting trial eligibility criteria (n = 19) to explore reasons for accepting or declining participation and with operating urologists (n = 15) to explore trial acceptability. Results: Patients expressed various preferences and understood these in the context of relative severity and tolerability of their symptoms. Accounts suggest a common trajectory of worsening symptoms with a particular window within which either treatment arm would be considered acceptable. Interviews with clinician recruiters found that uncertainty varied between general and specialist sites, which reflect clinicians' relative exposure to different proportions of the patient population. Conclusion: Recruitment post referral, at specialist sites, was challenging due to patient (and clinician) expectations. Trial design, particularly where there are fixed points for recruitment along the care pathway, can enable or constrain the possibilities for effective accrual depending on how it aligns with the optimum point of patient equipoise. Qualitative recruitment investigations, often focussed on information provision and patient engagement, may also look to better understand the target patient population in order to optimise the point at which patients are approached. Trial registration: ISRCTN Registry, ISRCTN98009168. Registered on 29 November 2012

    Pneumolysin Activates the NLRP3 Inflammasome and Promotes Proinflammatory Cytokines Independently of TLR4

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    Pneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1ÎČ, IL-1α and TNF-α by DC and enhanced cytokines including IL-17A and IFN-Îł by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-Îł are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-Îł and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1ÎČ plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1ÎČ secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system
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