The role of Transient Receptor Potential (TRP) channels in the pathogenesis of COPD

COPD is currently the 4th most prevalent cause of death worldwide. Despite the global impact, there are no currently available treatments which impede disease progression. This lack of effective therapies is largely due to an inadequate understanding of the mechanisms which drive disease progression. Cigarette smoke (CS), the most important risk factor for COPD, is thought to initiate an inflammatory response in the lungs which becomes self-propagating and dysregulated. Chronically, this inflammatory response drives structural and functional changes. The mechanisms by which CS elicits this inflammatory response, however, remain unclear. Certain CS constituents are known to activate Transient Receptor Potential (TRP) ion channels. A number of TRP channels are actively expressed in the lung tissue or inflammatory cells, and a further few are also implicated in the generation of inflammation. Owing to these features, it was hypothesised that TRP channels A1, C6, M2, M8, V1 and V4 have a role in CS-induced airway inflammation and, consequently, the pathogenesis of COPD. To test this hypothesis, three murine models of induced airway inflammation were characterised: acute CS, sub-chronic CS and endotoxin (LPS). Lung-tissue TRP channel expression levels were measured in these models alongside human lung-parenchyma samples from non-smokers, smokers and emphysema patients. Mice deficient for specific TRP channels were profiled in the CS-model and the LPS-model to establish the role of TRP channels in the initiation of inflammation in disease and non-disease settings. TRPV1-/-, TRPV4-/- and TRPM8-/- mice exhibited significantly reduced levels of airway inflammation compared to wild-types after acute CS, but normal responses to the innate (LPS) challenge. This data suggests that modulation of TRP channels could represent a novel anti-inflammatory approach for combating smoke induced diseases like COPD without impacting on the normal, essential innate defence mechanisms.Open Acces

Ion-Atom Collisions: A Time-Dependent Density-Functional-Theory Perspective

Time-dependent density functional theory (TDDFT) is an alternate formulation of time-dependent N-body quantum mechanics which allows one to describe a system via the single-particle density, n, rather than the full N-body wave function. While this reformulation is in theory exact in practice it necessitates at least two approximations. First, the exchange-correlation potential which encodes the two-particle interactions present in the time-dependent Schrdinger equation into the language of the single-particle description is not precisely known. Even if one had perfect knowledge of this potential a further approximation would be required when attempting to extract the values of observables as the exact relation between the one-particle density and most observables of interest is also unknown. This dissertation investigates these issues using ion-atom collision systems as a testbed. First, the observable problem is explored in antiproton-helium, proton-helium, and He^{2+}-He collision systems. Total cross sections for all charge transfer processes in these systems, the observables of choice in the present situation, are determined using a two-centred extension of a correlation-integral model that was originally applied to single-centred situations. Following this theoretical total cross section results for all ionization/capture processes in the He^{+}-He collision system are presented in the approximate impact energy range 10-1000 keV/amu. Calculations were performed within the framework of a spin-dependent extension of TDDFT. These cross sections are used as a benchmark to test an accurate exchange-correlation potential generated via the Krieger-Li-Iafrate approximation applied within the exchange-only limit in which correlation is ignored. The results of two models, one where electron translation factors in the orbitals used to calculate the potential are ignored and another where partial electron translation factors are included, are compared with available experimental data as well as a selection of previous theoretical calculations

What factors are associated with ambulance use for non-emergency problems in children?:A systematic mapping review and qualitative synthesis

Objective To explore what factors are associated with ambulance use for non-emergency problems in children. Methods This study is a systematic mapping review and qualitative synthesis of published journal articles and grey literature. Searches were conducted on the following databases, for articles published between January 1980 and July 2020: MEDLINE, EMBASE, PsycINFO, CINAHL and AMED. A Google Scholar and a Web of Science search were undertaken to identify reports or proceedings not indexed in the above. Book chapters and theses were searched via the OpenSigle, EThOS and DART databases. A literature advisory group, including experts in the field, were contacted for relevant grey literature and unpublished reports. The inclusion criteria incorporated articles published in the English language reporting findings for the reasons behind why there are so many calls to the ambulance service for non-urgent problems in children. Data extraction was divided into two stages: extraction of data to generate a broad systematic literature € map', and extraction of data from highly relevant papers using qualitative methods to undertake a focused qualitative synthesis. An initial table of themes associated with reasons for non-emergency calls to the ambulance for children formed the € thematic map' element. The uniting feature running through all of the identified themes was the determination of € inappropriateness' or € appropriateness' of an ambulance call out, which was then adopted as the concept of focus for our qualitative synthesis. Results There were 27 articles used in the systematic mapping review and 17 in the qualitative synthesis stage of the review. Four themes were developed in the systematic mapping stage: socioeconomic status/geographical location, practical reasons, fear of consequences and parental education. Three analytical themes were developed in the qualitative synthesis stage including practicalities and logistics of obtaining care, arbitrary scoring system and retrospection. Conclusions There is a lack of public and caregiver understanding about the use of ambulances for paediatrics. There are factors that appear specific to choosing ambulance care for children that are not so prominent in adults (fever, reassurance, fear of consequences). Future areas for attention to decrease ambulance activation for paediatric low-acuity reports were highlighted as: identifying strategies for helping caregivers to mitigate perceived risk, increasing availability of primary care, targeted education to particular geographical areas, education to first-time parents with infants and providing alternate means of transportation. PROSPERO registration number CRD42019160395

Improving the effectiveness of public health infographics through design principle application

Infographics have been recognised as an effective and accessible method of information communication, leading to their common use in the dissemination of public health information. However, current design outputs in this field are not frequently produced by information design specialists, resulting in variable design quality. This project looked to address this problem, by investigating the development process for a tool that would allow such users with limited design training to maximise the effectiveness of their infographic outputs. First, a literature review was conducted to define research-based design principles that were applicable to infographics. The value of these principles was then investigated, experimentally comparing user performance with 3 infographic design variations. These design variations applied the design principles to variable degrees; establishing that a high proportion of principles should be applied to maximise user performance. Next, the principles were reduced from 84 to 20, aiming to retain the most salient and maximising accessibility for the non-designer audience. These final principles were developed into motion graphic education resource, aiming to optimise adherence and teach this demographic to successfully apply the principles in their own design. The resource was later tested by conducting a generative design investigation that required 9 healthcare professionals to design a public health infographic, both before and after accessing the resource. Comparative experimental testing on these design outputs revealed that use of the motion graphics resulted in significantly more effective designs, measured by information location efficiency, memorability, and user opinion. This established a successful process for developing effective design education tools, and identified motion graphics as an efficient teaching technique. As well as establishing the needs of the healthcare professional target audience through an iterative user-centred design process. Finally, concluding that use of this resource can be used to maximise the effectiveness of public health infographics, providing potential advantages to the prevention of future disease and protection of the public health

Damage assessment by Acoustic Emission (AE) during landing gear fatigue testing.

Keywords: Acoustic Emission, Aerospace Components, Damage Detection, Fatigue, Source Location, AT mapping

Entanglement Induced Phase Transitions

Starting from the canonical ensemble over the space of pure quantum states, we obtain an integral representation for the partition function. This is used to calculate the magnetisation of a system of N spin-1/2 particles. The results suggest the existence of a new type of first order phase transition that occurs at zero temperature in the absence of spin-spin interactions. The transition arises as a consequence of quantum entanglement. The effects of internal interactions are analysed and the behaviour of the magnetic susceptibility for a small number of interacting spins is determined.Comment: 4 pages, 2 figure

Measuring the socio-economic status of women across the life course

This article highlights findings from the 2014 study Socio-Economic Status of Women Across the Life Course in NSW, which examined the main measurement issues that arise when assessing the socio-economic status of women over the life course and determining the "best" indicators. This article reviews some of the issues and presents selected findings relating to women of low socio-economic status in different life-stage groups. The study was commissioned by Women NSW and conducted by the Australian Institute of Family Studies.The authors would like to acknowledge the contribution of colleagues at the Australian Institute of Family Studies (AIFS) and of the members of the Expert Advisory Group on the Socio-Economic Status of Women in NSW, each of whom provided invaluable advice and guidance