392 research outputs found

    Censorship and the political cartoonist

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    Adelaide, S

    Introduction: Controversial Images

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    © 2008 Copyright is vested in the authors. Apart from any fair dealing permitted according to the provisions of the Copyright Act, reproduction by any process of any part of the work may not be undertaken without written permission from the copyright holders of Comic Commentators.There appears to be a growing sensitivity to cartoons’ potential impact in public debate, and so it is a good time to ask what the role of cartoons is in Australian politics, policy and media. This collection brings together cartoonists, media professionals and researchers all, in their different ways, fascinated by the contribution cartoons make to our public life. The range of backgrounds of the contributors has led to a rich range of writing styles and approaches; as editors, we have not sought to impose a uniform method on the chapters, but have especially encouraged the cartoonists and media professionals to write from their experience rather than in an imitation of academic style.Pert

    Plasticity in transmission strategies of the malaria parasite, Plasmodium chabaudi : environmental and genetic effects

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    Parasites may alter their behaviour to cope with changes in the within-host environment. In particular, investment in transmission may alter in response to the availability of parasite resources or host immune responses. However, experimental and theoretical studies have drawn conflicting conclusions regarding parasites' optimal (adaptive) responses to deterioration in habitat quality. We analyse data from acute infections with six genotypes of the rodent malaria species to quantify how investment in transmission (gametocytes) is influenced by the within-host environment. Using a minimum of modelling assumptions, we find that proportional investment in gametocytogenesis increases sharply with host anaemia and also increases at low parasite densities. Further, stronger dependence of investment on parasite density is associated with greater virulence of the parasite genotype. Our study provides a robust quantitative framework for studying parasites' responses to the host environment and whether these responses are adaptive, which is crucial for predicting the short-term and evolutionary impact of transmission-blocking treatments for parasitic diseases

    Eftilagimod alpha, a soluble lymphocyte activation gene-3 (LAG-3) protein plus pembrolizumab in patients with metastatic melanoma

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    © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine plasma pharmacokinetic parameters, detect efti antibody formation and determine long-lived CD8 T cell responses and associated pharmacodynamic parameters. RESULTS: Twenty-four patients with melanoma received pembrolizumab and bi-weekly subcutaneous (s.c.) injections of efti at doses 1 mg, 6 mg or 30 mg/injection for up to 6 months (part A) or 30 mg/injection for up 12 months (part B). No dose-limiting toxicities were reported and the main adverse event for efti was injection site reactions. Sustained systemic exposure to the product was obtained in all patients following s.c. injections of 30 mg dose. Treatment induced an increase in activated CD8 and CD4 T cell counts, and in some of the soluble biomarkers, particularly interferon (IFN)-γ, a Th1 signature cytokine. An overall response rate (ORR) of 33% was observed in patients partly with pembrolizumab-refractory of part A and ORR of 50% was observed in patients with PD-1 naïve of part B. CONCLUSIONS: Efti was well tolerated in combination with pembrolizumab with encouraging antitumor activity. This warrants further clinical studies of this new combination therapy combining an antigen-presenting cell activator with an immune checkpoint inhibitor

    Persistence in epidemic metapopulations: quantifying the rescue effects for measles, mumps, rubella and whooping cough

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    Metapopulation rescue effects are thought to be key to the persistence of many acute immunizing infections. Yet the enhancement of persistence through spatial coupling has not been previously quantified. Here we estimate the metapopulation rescue effects for four childhood infections using global WHO reported incidence data by comparing persistence on island countries vs all other countries, while controlling for key variables such as vaccine cover, birth rates and economic development. The relative risk of extinction on islands is significantly higher, and approximately double the risk of extinction in mainland countries. Furthermore, as may be expected, infections with longer infectious periods tend to have the strongest metapopulation rescue effects. Our results quantitate the notion that demography and local community size controls disease persistence

    Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

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    Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

    A topical review of the feasibility and reliability of ambulance-based telestroke

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    BackgroundAmbulance-based telemedicine is an innovative strategy through which transport time can be used to rapidly and accurately triage stroke patients (i.e., mobile telestroke). The acute phase of stroke is a time-sensitive emergency, and delays in care during this phase worsen outcomes. In this literature review, we analyzed studies that investigated the feasibility and reliability of ambulance based telestroke.MethodsWe followed PRISMA guidelines to perform a keyword-based search of PubMed, Web of Science, CINHAL, and Academic Search Complete databases. We reviewed references of search-identified articles to screen for additional articles. Articles for inclusion were selected according to author consensus in consideration of the studies' investigation of feasibility, reliability, or validity of ambulance-based telestroke.ResultsWe identified 67 articles for secondary screening from which 19 articles were selected for full text review. The selected studies reported diverse methods of development, implementation, and assessment of ambulance-based telestroke systems. Although the methods and results varied among these studies, most concluded that the implementation of ambulance based telestroke is feasible.ConclusionThis topical review suggests that ambulance based telestroke is a feasible method for enhanced prehospital stroke care in a variety of settings. Further prospective research is needed to assess the real-world challenges and to identify additional strategies that bolster rapid and accurate prehospital assessment of acute stroke patients
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