Infection-induced IL-10 and Jak-Stat: A review of the molecular circuitry controlling immune hyperactivity in response to pathogenic microbes

Generation of effective immune responses against pathogenic microbes depends on a fine balance between pro- and anti-inflammatory responses. Interleukin-10 (IL-10) is essential in regulating this balance and has garnered renewed interest recently as a modulator of the response to infection at the JAK-STAT signaling axis of host responses. Here, we examine how IL-10 functions as the “master regulator” of immune responses through JAK-STAT, and provide a perspective from recent insights on bacterial, protozoan, and viral infection model systems. Pattern recognition and subsequent molecular events that drive activation of IL-10-associated JAK-STAT circuitry are reviewed and the implications for microbial pathogenesis are discussed.

Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

Response: Special communication: Letters to the Editor-in-Chief [Vigorous exercise in clinical practice: balancing risks and benefits]

The effects of different exercise intensities on health have been investigated in several studies in recent years, in which some authors showed greater benefits for vigorous exercise (6) while others did not find any differences (8). An important issue regarding these conflicting results could be the fact that only a few of the studies controlled the effects of different exercise intensities for the overall volume of physical activity, making the evaluation of the available data difficult.

The Politics of Surveillance and Response to Disease Outbreaks: The New Frontier for States and Non-state Actors

The capacity to conduct international disease outbreak surveillance and share information about outbreaks quickly has empowered both State and Non-State Actors to take an active role in stopping the spread of disease by generating new technical means to identify potential pandemics through the creation of shared reporting platforms. Despite all the rhetoric about the importance of infectious disease surveillance, the concept itself has received relatively little critical attention from academics, practitioners, and policymakers. This book asks leading contributors in the field to engage with five key issues attached to international disease outbreak surveillance - transparency, local engagement, practical needs, integration, and appeal - to illuminate the political effect of these technologies on those who use surveillance, those who respond to surveillance, and those being monitored.

In response: UV–vis light transmittance through tinted contact lenses and the effect of color on values

In the study, we used the Agilent 8453 spectrophotometer (which is equipped with a limiting aperture that restricts the light beam to the central 5 mm of the contact lens), to measure the transmittance of various coloured contact lenses including the one Day Acuvue define manufactured by Johnson and Johnson which the authors represent. We measured the instrument baseline before the transmittance spectra of lenses were tested. The values of lens transmittances were thus the difference between baseline and lens measurement at each time. The transmittance measurements were obtained at 0.5 nm intervals, from 200 to 700 nm after a soak in saline to remove the influence of any surface active agents within the packaging products. The technique used in our study was not very different from how other research studies [2], [3], [4], [5] and [6] have measured the spectra transmittances of contact lenses...

Liberty

In terms of critical discourse, Liberty contributes to the ongoing aesthetic debate on ‘the sublime.’ Philosopher Immanuel Kant (1724–1804) defined the sublime as a failure of rationality in response to sensory overload: a state where the imagination is suspended, without definitive reference points—a state beyond unequivocal ‘knowing.’ I believe the events of September 11, 2001 eluded our understanding in much the same way, leaving us in a moment of suspension between awe and horror. It was an event that couldn’t be understood in terms of scope or scale. It was a moment of overload, which is so difficult to capture in art. With my work I attempt to rekindle that moment of suspension. Like the events of 9/11, Liberty defies definition. Its form is constantly changing; it is always presenting us with new layers of meaning. Nobody quite had a handle on the events that followed 9/11, because the implications were constantly shifting. In the same way, Liberty cannot be contained or defined at any moment in time. Like the events of 9/11, the full story cannot be told in a snapshot. One of the dictionary definitions for the word ‘sublime’ is the conversion of ‘a solid substance directly into a gas, without there being an intermediate liquid phase’. With this in mind, I would like to present Liberty as a work that is literally ‘sublime.’ But what’s really interesting to me about Liberty is that it presents the sublime on all levels: in its medium, in its subject matter (that moment of suspension), and in its formal (formless) presentation. On every level Liberty is sublime—subverting all tangible reference points and eluding capture entirely. Liberty is based on the Statue of Liberty in New York. However, unlike that statue which has stood in New York since 1886 and can be reasonably expected to stand for millennia, this work takes on diminishing proportions, carved as it is in carbon dioxide, a mysterious, previously unexplored medium—one which smokes, snows and dramatically vanishes into a harmless gas. Like the material this work is carved from, the civil liberties of the free world are diminishing fast, since 9/11 and before. This was my thought when I first conceived this work. Now it’s become evident that Liberty expresses a lot more than just this: it demonstrates the erosion of civil liberties, yes. However, it also presents the intangible, indefinable moments in the days and months that followed 9/11. The sculptural work will last for only a short time, and thereafter will exist only in documentation. During this time, the form is continually changing and self-refining, until it disappears entirely, to be inhaled, metabolised and literally taken to heart by viewers.

Response of the anterior sclera to accommodation in myopes and emmetropes

• The biomechanical properties of the sclera are documented to be altered in eyes with myopia, with the myopic sclera thought to be more susceptible to deformation from otherwise normal ocular forces. • The close anatomical and functional relationship between the ciliary body and sclera suggests that ciliary muscle contraction during accommodation may influence the overlying sclera. • This study aimed to characterise the changes occurring in anterior scleral thickness with accommodation using anterior segment optical coherence tomography (AS-OCT) in young adult myopes and emmetropes.

Threshold level of defocus to produce an accommodation response

To investigate the threshold level of defocus that induces a measurable objective change in accommodation response to a target at an intermediate distance.

The role of MicroRNAs in stress response in the resurrection plant Tripogon loliiformis

Research in this thesis focussed on the improvement of agricultural crops in increasing water use efficiency that impacts global crop productivity. The study identified key genetic regulatory mechanisms that the resurrection plant Tripogon loliiformis utilises to tolerate desiccation. Due to the conserved nature of the pathways involved, this information can be transferred for the enhancement of drought tolerance and water use efficiency in agricultural crops. Specifically this study used high throughput sequencing, microscopy and plant transformation to further the understanding of post-transcriptional regulatory mechanisms. It was shown that T. loliiformis uses microRNAs to regulate pro-survival autophagy pathways to tolerate desiccation.

Assessing taxpayer response to legislative changes: A case study of ‘in-house’ fringe benefits rules

On 22 October 2012, the Australian Federal Government announced the removal of the $1,000 in-house fringe benefits concession when used as part of a salary packaging arrangement. At the time of the announcement, the Federal Government predicted that the removal of the concession would contribute additional tax revenue of $445 million over the following four years as well as an increase of GST payments to the States and Territories. However, anecdotal evidence at the same time indicated that the Australian employer response was to immediately stop providing employees with such in-house fringe benefits via salary sacrificing arrangements. Data presented in this article, collected from a combination of interviews with tax managers of four Australian entities as well as a review of the published archival data, confirms that the abolition of the $1,000 in-house fringe benefits concession was perceived as a negative change, whereby employees were considered the ‘big losers’ despite assertions by the Federal Government to the contrary. Using a conceptual map of tax rule change developed by Oats and Sadler, this article seeks to understand the reasons for this fringe benefits tax change and taxpayer response. In particular, the economic and political factors, and the responses of the relevant taxpayers (employers) are explored. Drawing on behavioural economic concepts, the actions, attitudes and response of employers to the rule change are also examined. The research findings suggest that the decision by Australian employers to cease providing the in-house fringe benefits as part of a salary-packaging arrangement after the legislative amendment was impacted by more than simple rational behaviour.

Animated Mise-en-scene and aesthetic harmony: An expansion of the traditional principles of animation to 3D computer animation

3D Computer Graphics (CG) has become the dominant medium for modern animated feature films. It is widely understood that traditional principles of animation developed in the 1930s at the Walt Disney Studio remain applicable to this new medium and heavily influence the range of aesthetic motion styles in contemporary animation. Via a frame-by-frame textual analysis of four animated feature films, this thesis tests and confirms the validity of the principles of animation and expands upon them by reinterpreting the Disney principle of appeal as aesthetic harmony, which delineates the way in which character posing and transitions between poses contribute to the animated motion styles that animators work in today.

Non-linear response of soil N2O emissions to nitrogen fertiliser in a cotton-fallow rotation in sub-tropical Australia

Nitrogen fertiliser is a major source of atmospheric N2O and over recent years there is growing evidence for a non-linear, exponential relationship between N fertiliser application rate and N2O emissions. However, there is still high uncertainty around the relationship of N fertiliser rate and N2O emissions for many cropping systems. We conducted year-round measurements of N2O emission and lint yield in four N rate treatments (0, 90, 180 and 270 kg N ha-1) in a cotton-fallow rotation on a black vertosol in Australia. We observed a nonlinear exponential response of N2O emissions to increasing N fertiliser rates with cumulative annual N2O emissions of 0.55 kg N ha-1, 0.67kg N ha-1, 1.07 kg N ha-1 and 1.89 kg N ha-1 for the four respective N fertiliser rates while no N response to yield occurred above 180N. The N fertiliser induced annual N2O EF factors increased from 0.13% to 0.29% and 0.50% for the 90N, 180N and 270N treatments respectively, significantly lower than the IPCC Tier 1 default value (1.0 %). This non-linear response suggests that an exponential N2O emissions model may be more appropriate for use in estimating emission of N2O from soils cultivated to cotton in Australia. It also demonstrates that improved agricultural N management practices can be adopted in cotton to substantially reduce N2O emissions without affecting yield potential.

Tripogon loliiformis elicits a rapid physiological and structural response to dehydration for desiccation tolerance

Resurrection plants can withstand extreme dehydration to an air-dry state and then recover upon receiving water. Tripogon loliiformis (F.Muell.) C.E.Hubb. is a largely uncharacterised native Australian desiccation-tolerant grass that resurrects from the desiccated state within 72 h. Using a combination of structural and physiological techniques the structural and physiological features that enable T. loliiformis to tolerate desiccation were investigated. These features include: - (i) a myriad of structural changes such as leaf folding, cell wall folding and vacuole fragmentation that mitigate desiccation stress; - (ii) potential role of sclerenchymatous tissue within leaf folding and radiation protection; - (iii) retention of ~70% chlorophyll in the desiccated state; - (iv) early response of photosynthesis to dehydration by 50% reduction and ceasing completely at 80 and 70% relative water content, respectively; - (v) a sharp increase in electrolyte leakage during dehydration, and; - (vi) confirmation of membrane integrity throughout desiccation and rehydration. Taken together, these results demonstrate that T. loliiformis implements a range of structural and physiological mechanisms that minimise mechanical, oxidative and irradiation stress. These results provide powerful insights into tolerance mechanisms for potential utilisation in the enhancement of stress-tolerance in crop plants.

Dance teacher education in the 21st century : Linking cultural and aesthetic practice

This paper describes the implementation of the recommendations of a series of research projects, within an undergraduate dance teacher-training course, into the training of collaborative, empathetic, ethical and creative dance teachers. Banks’s Dimensions for Multicultural Education (Banks, 1993) was used as a lens to analyze the design and delivery of cultural dance activities within a university dance-teaching unit, implemented in Australia and Timor Leste, and to reflect on the adaptability of the Performance in Context Model (Stevens & Huddy, in press) across different cultural contexts. Content and contextual knowledge, transformational learning pedagogy, teaching for equity and empathy development were explored through a culturally responsive teaching and learning unit, supported by critical analysis and reflection. This analysis identified a number of key understandings in relation to the design and delivery of cultural dance activities.

Potential antioxidant response to coffee - A matter of genotype?

In a human intervention trial, a coffee, combining nature green coffee bean constituents and dark roast products was studied towards its potential to activate the Nrf2/ARE-pathway in PBLs. The study coffee was identified as a strong inducer of Nrf2 and downstream GST1A1 and UGT1A1 gene transcription. However, the response of the participants was found to depend on the respective genotype. The -651 SNP in the Nrf2 gene as well as the heterozygote 6/7 sequence in the UGT1A1 gene significantly down-regulated the susceptibility to respond to coffee, proposing the existing genotype to be critical for the response to the coffee.