A Very Radio-Loud Narrow-Line Seyfert 1: PKS 2004-447

We have discovered a very radio-loud Narrow-Line Seyfert 1 candidate: PKS 2004-447. This Seyfert is consistent with the formal definition for NLS1s, although it does not have quite the same spectral features as some typical members of this subclass. Only ROSAT survey data is available at X-ray wavelengths, so it has not been possible to compare this source with other NLS1s at these wavelengths. A full comparison of this source with other members of the subclass will improve our physical understanding of NLS1s. In addition, using standard calculations, we estimate the central black hole to have a mass of $\sim 5 \times 10^6 M_{\odot}$. This does not agree with predictions in the literature, that radio-loud AGN host very massive black holes.Comment: 15 pages, 4 figures, accepted for publication in ApJ, minor typos change

An early developmental vertebrate model for nanomaterial safety:Bridging cell-based and mammalian toxicity assessment

Background. With the rise in production of nanoparticles for an ever-increasing number of applications, there is an urgent need to efficiently assess their potential toxicity. We propose a nanoparticle hazard assessment protocol that combines mammalian cytotoxicity data with embryonic vertebrate abnormality scoring to determine an overall toxicity index. Results. We observed that, after exposure to a range of nanoparticles, Xenopus phenotypic scoring showed a strong correlation with cell based in vitro assays. Magnetite-cored nanoparticles, negative for toxicity in vitro and Xenopus, were further confirmed as non-toxic in mice. Conclusion. The results highlight the potential of Xenopus embryo analysis as a fast screening approach for toxicity assessment of nanoparticles, which could be introduced for the routine testing of nanomaterials

Identification of the factors associated with outcomes in a condition management programme

<p>Background: A requirement of the Government’s Pathways to Work (PtW) agenda was to introduce a Condition Management Programme (CMP). The aim of the present study was to identify the differences between those who engaged and made progress in this telephone-based biopsychosocial intervention, in terms of their health, and those who did not and to determine the client and practitioner characteristics and programme elements associated with success in a programme aimed at improving health.</p> <p>Methods: Data were obtained from the CMP electronic spreadsheets and clients paper-based case records. CMP standard practice was that questionnaires were administered during the pre- and post-assessment phases over the telephone. Each client’s record contains their socio-demographic data, their primary health condition, as well as the pre- and post-intervention scores of the health assessment tool administered. Univariate and multivariate statistical analysis was used to investigate the relationships between the database variables. Clients were included in the study if their records were available for analysis from July 2006 to December 2007.</p> <p> Results: On average there were 112 referrals per month, totalling 2016 referrals during the evaluation period. The majority (62.8%) of clients had a mental-health condition. Successful completion of the programme was 28.5% (575 “completers”; 144 “discharges”). Several factors, such as age, health condition, mode of contact, and practitioner characteristics, were significant determinants of participation and completion of the programme. The results showed that completion of the CMP was associated with a better mental-health status, by reducing the number of clients that were either anxious, depressed or both, before undertaking the programme, from 74% to 32.5%.</p> <p>Conclusions: Our findings showed that an individual's characteristics are associated with success in the programme, defined as completing the intervention and demonstrating an improved health status. This study provides some evidence that the systematic evaluation of such programmes and interventions could identify ways in which they could be improved.</p&gt

A survey for redshifted molecular and atomic absorption lines I

We are currently undertaking a large survey for redshifted atomic and molecular absorption ... only one clear and one tentative detection were obtained: HI absorption at z = 0.097 in PKS 1555-140 and OH absorption at z =0.126 in PKS 2300-189, respectively... In order to determine why no clear molecular absorption was detected in any of the 13 sources searched, we investigate the properties of the five redshifted systems currently known to exhibit OH absorption. In four of these, molecules were first detected via millimetre-wave transitions and the flat radio spectra indicate compact background continuum sources, which may suggest a high degree of coverage of the background source by the molecular clouds in the absorber. Furthermore, for these systems we find a relationship between the molecular line strength and red optical--near infrared (V-K) colours, thus supporting the notion that the reddening of these sources is due to dust, which provides an environment conducive to the formation of molecules. Upon comparison with the V-K colours of our sample, this relationship suggests that, presuming the reddening occurs at the host galaxy redshift at least in some of the targets, many of our observations still fall short of the sensitivityrequired to detect OH absorption, although a confirmation of the ``detection'' of OH in 2300-189 could contravene this.Comment: 13 pages, loads of figures, accepted by MNRA

Development of a Series of Kynurenine 3-Monooxygenase Inhibitors Leading to a Clinical Candidate for the Treatment of Acute Pancreatitis

Recently, we reported a novel role for KMO in the pathogenesis of acute pancreatitis (AP). A number of inhibitors of kynurenine 3-monooxygenase (KMO) have previously been described as potential treatments for neurodegenerative conditions and particularly for Huntington's disease. However, the inhibitors reported to date have insufficient aqueous solubility relative to their cellular potency to be compatible with the intravenous (iv) dosing route required in AP. We have identified and optimized a novel series of high affinity KMO inhibitors with favorable physicochemical properties. The leading example is exquisitely selective, has low clearance in two species, prevents lung and kidney damage in a rat model of acute pancreatitis, and is progressing into preclinical development.</p

Q Fever Update, Maritime Canada

Since the 1990s, reports of Q fever in Nova Scotia, Canada, have declined. Passive surveillance for Q fever in Nova Scotia and its neighboring provinces in eastern Canada indicates that the clinical manifestation of Q fever in the Maritime provinces is pneumonia and that incidence of the disease may fluctuate

Determining the mode of action of anti-mycobacterial C17 diyne natural products using expression profiling: evidence for fatty acid biosynthesis inhibition

BACKGROUND: The treatment of microbial infections is becoming increasingly challenging because of limited therapeutic options and the growing number of pathogenic strains that are resistant to current antibiotics. There is an urgent need to identify molecules with novel modes of action to facilitate the development of new and more effective therapeutic agents. The anti-mycobacterial activity of the C17 diyne natural products falcarinol and panaxydol has been described previously; however, their mode of action remains largely undetermined in microbes. Gene expression profiling was therefore used to determine the transcriptomic response of Mycobacterium smegmatis upon treatment with falcarinol and panaxydol to better characterize the mode of action of these C17 diynes. RESULTS: Our analyses identified 704 and 907 transcripts that were differentially expressed in M. smegmatis after treatment with falcarinol and panaxydol respectively. Principal component analysis suggested that the C17 diynes exhibit a mode of action that is distinct to commonly used antimycobacterial drugs. Functional enrichment analysis and pathway enrichment analysis revealed that cell processes such as ectoine biosynthesis and cyclopropane-fatty-acyl-phospholipid synthesis were responsive to falcarinol and panaxydol treatment at the transcriptome level in M. smegmatis. The modes of action of the two C17 diynes were also predicted through Prediction of Activity Spectra of Substances (PASS). Based upon convergence of these three independent analyses, we hypothesize that the C17 diynes inhibit fatty acid biosynthesis, specifically phospholipid synthesis, in mycobacteria. CONCLUSION: Based on transcriptomic responses, it is suggested that the C17 diynes act differently than other anti-mycobacterial compounds in M. smegmatis, and do so by inhibiting phospholipid biosynthesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2949-y) contains supplementary material, which is available to authorized users

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Re-stating the post-political: depoliticization, social inequalities, and city-region growth

This paper argues that city-region building debates and relatedly ‘post-political’ literatures are missing critical perspectives on the state, particularly the state’s continued existence as a social relation and an arena for politics, its role in the regulation of uneven development and the conflicts and struggles that arise from this. The paper brings the state centrally into ‘post-political’ debates via a critical analysis of the interrelationships between depoliticization and neoliberalism. Focusing on Sheffield (South Yorkshire, England) in the context of devolution and deal-making public policy, the paper explores the seemingly consensual visionmaking dynamics of this city region and dissects the tensions around economic governance, welfare austerity and social inequalities to get a handle on the ‘postpolitical’ depoliticized state in, and of, contemporary capitalism

Modifying bacterial flagellin to evade Nod-like Receptor CARD 4 recognition enhances protective immunity against Salmonella.

Pattern recognition receptors (PRRs) expressed in antigen-presenting cells are thought to shape pathogen-specific immunity by inducing secretion of costimulatory cytokines during T-cell activation, yet data to support this notion in vivo are scarce. Here, we show that the cytosolic PRR Nod-like Receptor CARD 4 (NLRC4) suppresses, rather than facilitates, effector and memory CD4+ T-cell responses against Salmonella in mice. NLRC4 negatively regulates immunological memory by preventing delayed activation of the cytosolic PRR NLR pyrin domain 3 (NLRP3) that would otherwise amplify the production of cytokines important for the generation of Th1 immunity such as intereukin-18. Consistent with a role for NLRC4 in memory immunity, primary challenge with Salmonella expressing flagellin modified to largely evade NLRC4 recognition notably increases protection against lethal rechallenge. This finding suggests flagellin modification to reduce NLRC4 activation enhances protective immunity, which could have important implications for vaccine development against flagellated microbial pathogens.Wellcome Trus