An association between the acute phase response and patterns of antigen induced T cell proliferation in juvenile idiopathic arthritis

The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients: a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested; and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association between the acute phase response and the T cell population recruited to an inflammatory site

Ionic gold demonstrates antimicrobial activity against Pseudomonas aeruginosa strains due to cellular ultrastructure damage

Due to the ever-increasing rise of antimicrobial resistant (AMR) bacteria, the development of alternative antimicrobial agents is a global priority. The antimicrobial activity of ionic gold was explored against four Pseudomonas aeruginosa strains with different AMR profiles in order to determine the antimicrobial activity of ionic gold and elucidate the mechanisms of action. Disc diffusion assays (zone of inhibition: ZoI) coupled with minimum inhibitory/bactericidal concentrations (MIC/MBC) were conducted to determine the antimicrobial efficacy of ionic gold. Scanning electron microscopy (SEM) was used to visualise morphological changes to the bacterial cell ultrastructure. Strains with increased AMR were slower to grow which is likely a fitness cost due to the enhanced AMR activity. Although greater concentrations of ionic gold were required to promote antimicrobial activity, ionic gold demonstrated similar antimicrobial values against all strains tested. Lowry assay results indicated that protein leakage was apparent following incubation with ionic gold, whilst SEM revealed cellular ultrastructure damage. This study suggests that the application of ionic gold as an alternative antimicrobial is promising, particularly against AMR P. aeruginosa. The antimicrobial activity of ionic gold against P. aeruginosa could potentially be utilised as an alternative therapeutic option in wound management, an approach that could benefit healthcare systems worldwide

Extent of publication bias in different categories of research cohorts: a meta-analysis of empirical studies.

BACKGROUND: The validity of research synthesis is threatened if published studies comprise a biased selection of all studies that have been conducted. We conducted a meta-analysis to ascertain the strength and consistency of the association between study results and formal publication. METHODS: The Cochrane Methodology Register Database, MEDLINE and other electronic bibliographic databases were searched (to May 2009) to identify empirical studies that tracked a cohort of studies and reported the odds of formal publication by study results. Reference lists of retrieved articles were also examined for relevant studies. Odds ratios were used to measure the association between formal publication and significant or positive results. Included studies were separated into subgroups according to starting time of follow-up, and results from individual cohort studies within the subgroups were quantitatively pooled. RESULTS: We identified 12 cohort studies that followed up research from inception, four that included trials submitted to a regulatory authority, 28 that assessed the fate of studies presented as conference abstracts, and four cohort studies that followed manuscripts submitted to journals. The pooled odds ratio of publication of studies with positive results, compared to those without positive results (publication bias) was 2.78 (95% CI: 2.10 to 3.69) in cohorts that followed from inception, 5.00 (95% CI: 2.01 to 12.45) in trials submitted to regulatory authority, 1.70 (95% CI: 1.44 to 2.02) in abstract cohorts, and 1.06 (95% CI: 0.80 to 1.39) in cohorts of manuscripts. CONCLUSION: Dissemination of research findings is likely to be a biased process. Publication bias appears to occur early, mainly before the presentation of findings at conferences or submission of manuscripts to journals

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Modelling the impact of improving screening and treatment of chronic hepatitis C virus infection on future hepatocellular carcinoma rates and liver-related mortality.

BACKGROUND: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. METHODS: A previously published model was adapted for England using published literature and government reports, and validated through an iterative process of three meetings of HCV experts. The impact of increasing diagnosis and treatment of HCV as new therapies become available was modelled and compared to the base-case scenario of continuing current management strategies. To assess the 'best case' clinical benefit of new therapies, the number of patients treated was increased by a total of 115% by 2018. RESULTS: In the base-case scenario, total viraemic (HCV RNA-positive) cases of HCV in England will decrease from 144,000 in 2013 to 76,300 in 2030. However, due to the slow progression of chronic HCV, the number of individuals with cirrhosis, decompensated cirrhosis and HCC will continue to increase over this period. The model suggests that the 'best case' substantially reduces HCV-related hepatic disease and HCV-related liver mortality by 2020 compared to the base-case scenario. The number of HCV-related HCC cases would decrease 50% by 2020 and the number progressing from infection to decompensated cirrhosis would decline by 65%. Therefore, compared to projections of current practices, increasing treatment numbers by 115% by 2018 would reduce HCV-related mortality by 50% by 2020. CONCLUSIONS: This analysis suggests that with current treatment practices the number of patients developing HCV-related cirrhosis, decompensated cirrhosis and HCC will increase substantially, with HCV-related liver deaths likely to double by 2030. However, increasing diagnosis and treatment rates could optimise the reduction in the burden of disease produced by the new therapies, potentially halving HCV-related liver mortality and HCV-related HCC by 2020

Rapid-response radio observations of short GRB 181123B with the Australia Telescope Compact Array

We introduce the Australia Telescope Compact Array (ATCA) rapid-response mode by presenting the first successful trigger on the short-duration gamma-ray burst (GRB) 181123B. Early-time radio observations of short GRBs may provide vital insights into the radio afterglow properties of Advanced LIGO- and Virgo-detected gravitational wave events, which will in turn inform follow-up strategies to search for counterparts within their large positional uncertainties. The ATCA was on target within 12.6 hr post-burst, when the source had risen above the horizon. While no radio afterglow was detected during the 8.3 hr observation, we obtained force-fitted flux densities of $7 \pm 12$ and $15 \pm 11~\mu$Jy at 5.5 and 9 GHz, respectively. Afterglow modelling of GRB 181123B showed that the addition of the ATCA force-fitted radio flux densities to the Swift X-ray Telescope detections provided more stringent constraints on the fraction of thermal energy in the electrons (log$\epsilon_e = -0.75^{+0.39}_{-0.40}$ rather than log$\epsilon_e = -1.13^{+0.82}_{-1.2}$ derived without the inclusion of the ATCA values), which is consistent with the range of typical $\epsilon_e$ derived from GRB afterglow modelling. This allowed us to predict that the forward shock may have peaked in the radio band $\sim10$ days post-burst, producing detectable radio emission $\gtrsim3-4$ days post-burst. Overall, we demonstrate the potential for extremely rapid radio follow-up of transients and the importance of triggered radio observations for constraining GRB blast wave properties, regardless of whether there is a detection, via the inclusion of force-fitted radio flux densities in afterglow modelling efforts

Trends in chlamydia and gonorrhea positivity among heterosexual men and men who have sex with men attending a large urban sexual health service in Australia, 2002-2009

<p>Abstract</p> <p>Background</p> <p>To determine whether chlamydia positivity among heterosexual men (MSW) and chlamydia and gonorrhea positivity among men who have sex with men (MSM), are changing.</p> <p>Methods</p> <p>Computerized records for men attending a large sexual health clinic between 2002 and 2009 were analyzed. Chlamydia and gonorrhea positivity were calculated and logistic regression used to assess changes over time.</p> <p>Results</p> <p>17769 MSW and 8328 MSM tested for chlamydia and 7133 MSM tested for gonorrhea. In MSW, 7.37% (95% CI: 6.99-7.77) were chlamydia positive; the odds of chlamydia positivity increased by 4% per year (OR = 1.04; 95% CI: 1.01-1.07; p = 0.02) after main risk factors were adjusted for. In MSM, 3.70% (95% CI: 3.30-4.14) were urethral chlamydia positive and 5.36% (95% CI: 4.82-5.96) were anal chlamydia positive; positivity could not be shown to have changed over time. In MSM, 3.05% (95% CI: 2.63-3.53) tested anal gonorrhea positive and 1.83% (95% CI: 1.53-2.18) tested pharyngeal gonorrhea positive. Univariate analysis found the odds of anal gonorrhea positivity had decreased (OR = 0.93; 95% CI: 0.87-1.00; p = 0.05), but adjusting for main risk factors resulted in no change. Urethral gonorrhea cases in MSM as a percentage of all MSM tested for gonorrhea also fell (p < 0.001).</p> <p>Conclusions</p> <p>These data suggest that chlamydia prevalence in MSW is rising and chlamydia and gonorrhea prevalence among MSM is stable or declining. High STI testing rates among MSM in Australia may explain differences in STI trends between MSM and MSW.</p