480 research outputs found

    Evaluation of ‘Stop Smoking in its Tracks’

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    This research was funded by a grant from the Australian Department of Health and Ageing. MP was funded by fellowships from the NHMRC, the Cancer Institute NSW and the Sydney Medical Foundation

    Serum Amyloid A induces toll-like receptor 2-dependent inflammatory cytokine expression and atrophy in C2C12 skeletal muscle myotubes

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    Background Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity. The direct effects of SAA on skeletal muscle are poorly understood. Here we have examined SAA effects on pro-inflammatory cachectic cytokine expression (IL-6 and TNFα) and atrophy in C2C12 myotubes. Results SAA increased IL-6 (31-fold) and TNFα (6.5-fold) mRNA levels compared to control untreated cells after 3h of SAA treatment, and increased secreted IL-6 protein at 24h. OxPAPC, a dual TLR2 and TLR4 inhibitor, reduced the response to SAA by approximately 84% compared to SAA alone, and the TLR2 neutralising antibody T2.5 abolished SAA-induced expression of IL-6, indicating that SAA signalling in C2C12 myotubes is primarily via TLR2. SAA also reduced myotube width by 10-13% and induced a 2.5-fold increase in the expression of the muscle atrophy gene Atrogin-1, suggesting direct effects of SAA on muscle wasting. Blocking of TLR2 inhibited the SAA-induced decrease in myotube width and Atrogin-1 gene expression, indicating that SAA induces atrophy through TLR2. Conclusions These data demonstrate that SAA stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the TLR2-dependent release of IL-6 and TNFα. Furthermore, the observed atrophy effects indicate that SAA could also be directly contributing to the wasting and poor recovery of muscle mass. Therapeutic strategies targeting this SAA-TLR2 axis may therefore ameliorate muscle wasting in AECOPD and a range of other inflammatory conditions associated with loss of m

    An absolute reference frame for clumped isotope thermometry

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    Analysis of multiply substituted isotopologues of molecules (‘clumped isotope geochemistry’) presents special challenges to both precision and accuracy. Previous discussions have focused on mass spectrometric precision for these rare species and intralaboratory reference frames. This discipline has spread, demanding interlaboratory standardization. We present a four-laboratory study of the calibration of mass-47 anomalies (Δ_(47) values) in CO_2 (especially extracted from carbonate). We consider: instrument linearity, source fragmentation/recombination reactions (which vary between mass spectrometers and with time and instrument settings), and differences in methods, materials and conditions for sample preparation. We address these problems by developing a method for standardizing Δ_(47) measurements to an absolute reference frame based on theoretical predictions of the abundances of multiply-substituted isotopologues of gaseous CO_2 that has reached a thermodynamic equilibrium at a known temperature. By analyzing CO_2 gases that have been subjected to established laboratory procedures known to promote isotopic equilibration (i.e., heated gases and water-equilibrated CO_2), and by reference to the statistical thermodynamic predictions of equilibrium isotopic distributions, it is possible to construct an empirical transfer function that can then be applied to CO_2 samples with unknown Δ_(47) values. This reference frame may be unique in that it is based on thermodynamic equilibrium, rather than the isotopic composition of an arbitrary reference material. We describe the protocol necessary to construct such a reference frame, the method for converting gases with unknown clumped isotope compositions to this frame, and suggest a protocol for ensuring that reported Δ_(47) values can be compared among different laboratories, independent of laboratory-specific analytical or methodological artefacts. Application of this approach to measurements of CO_2 extracted from several carbonate reference materials results in interlaboratory agreement on their Δ_(47) values to within est. ±0.01 ‰, 1σ. Finally, we present a revised paleotemperature scale that applies when using the absolute reference frame described here, as opposed to the previous paleotemperature equation based on data from a single laboratory. More generally, this study presents a model for how interlaboratory standardization might be approached for other ‘clumped isotope’ measurements

    High-temperature environments of human evolution in East Africa based on bond ordering in paleosol carbonates

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    Many important hominid-bearing fossil localities in East Africa are in regions that are extremely hot and dry. Although humans are well adapted to such conditions, it has been inferred that East African environments were cooler or more wooded during the Pliocene and Pleistocene when this region was a central stage of human evolution. Here we show that the Turkana Basin, Kenya—today one of the hottest places on Earth—has been continually hot during the past 4 million years. The distribution of ^(13)C-^(18)O bonds in paleosol carbonates indicates that soil temperatures during periods of carbonate formation were typically above 30 °C and often in excess of 35 °C. Similar soil temperatures are observed today in the Turkana Basin and reflect high air temperatures combined with solar heating of the soil surface. These results are specific to periods of soil carbonate formation, and we suggest that such periods composed a large fraction of integrated time in the Turkana Basin. If correct, this interpretation has implications for human thermophysiology and implies a long-standing human association with marginal environments

    Getting the Message Across for Safer Self-Recovery in Post-Disaster Shelter

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    Self-recovery in post-disaster shelter is not the exception but the norm. Following earthquake, flood or storm, the majority of affected families will inevitably rebuild their homes themselves, using their own resources, but there is little support from the international community to encourage good safe building practice. While the communication of key messages about safer building has been carried out effectively in development contexts, it rarely forms a major part of humanitarian response programming. If the humanitarian shelter sector is committed to the principles of Disaster Risk Reduction (DRR), more can be done to support the process of safer reconstruction among self-rebuilders. This paper argues the case for the humanitarian community to link post-disaster shelter programming with the more developmental approach of communicating building safety to a much wider audience than just the most vulnerable beneficiaries. It proposes the shelter sector and the donor community direct more resources towards support for this process, which it argues would augment the effectiveness and impact of a shelter response

    Smoking Mull: a grounded theory model on the dynamics of combined tobacco and cannabis use among men

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    Issue addressed: Australians’ use of cannabis has been increasing. Over a third of Australians (35.4%) have used cannabis at some time in their lives and 10.3% are recent users. Almost two-thirds of cannabis users combine cannabis with tobacco. The aim of this study was to understand the process of mulling – smoking tobacco and cannabis together – using a grounded theory approach. Methods: Twenty-one in-depth semi structured interviews were conducted with men aged 25–34 and living on the North Coast of New South Wales. Interviews explored participants’ smoking practices, histories and cessation attempts. Results: A model describing mulling behaviour and the dynamics of smoking cannabis and tobacco was developed. It provides an explanatory framework that demonstrates the flexibility in smoking practices, including substance substitution – participants changed the type of cannabis they smoked, the amount of tobacco they mixed with it and the devices they used to smoke according to the situations they were in and the effects sought. Conclusion: Understanding these dynamic smoking practices and the importance of situations and effects, as well as the specific role of tobacco in mulling, may allow health workers to design more relevant and appropriate interventions. So what?: Combining tobacco with cannabis is the most common way of smoking cannabis in Australia. However, tobacco cessation programmes rarely address cannabis use. Further research to develop evidence-based approaches for mull use would improve cessation outcomes. Keywords: concomitant use, marijuana, mulling, nicotineNHMR

    Economic costs of chronic disease through lost productive life years (PLYs) among Australians aged 45–64 years from 2015 to 2030:Results from a microsimulation model

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    Objectives: To project the number of older workers with lost productive life years (PLYs) due to chronic disease and resultant lost income; and lost taxes and increased welfare payments from 2015 to 2030. Design, setting and participants: Using a microsimulation model, Health&WealthMOD2030, the costs of chronic disease in Australians aged 45–64 were projected to 2030. The model integrates household survey data from the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers (SDACs) 2003 and 2009, output from long-standing microsimulation models (STINMOD (Static Incomes Model) and APPSIM (Australian Population and Policy Simulation Model)) used by various government departments, population and labour force growth data from Treasury, and disease trends data from the Australian Burden of Disease and Injury Study (2003). Respondents aged 45–64 years in the SDACs 2003 and 2009 formed the base population. Main outcome measures: Lost PLYs due to chronic disease; resultant lost income, lost taxes and increased welfare payments in 2015, 2020, 2025 and 2030. Results: We projected 380 000 (6.4%) people aged 45–64 years with lost PLYs in 2015, increasing to 462 000 (6.5%) in 2030—a 22% increase in absolute numbers. Those with lost PLYs experience the largest reduction in income than any other group in each year compared to those employed full time without a chronic disease, and this income gap widens over time. The total economic loss due to lost PLYs consisted of lost income modelled at A12.6billionin2015,increasingtoA12.6 billion in 2015, increasing to A20.5 billion in 2030—a 62.7% increase. Additional costs to the government consisted of increased welfare payments at A6.2billionin2015,increasingtoA6.2 billion in 2015, increasing to A7.3 billion in 2030—a 17.7% increase; and a loss of A3.1billionintaxesin2015,increasingtoA3.1 billion in taxes in 2015, increasing to A4.7 billion in 2030—a growth of 51.6%. Conclusions: There is a need for greater investment in effective preventive health interventions which improve workers’ health and work capacity.Full Tex

    Pre-service teachers’ engagement in a cross-curricular television news project: impact on professional identity

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    This paper focuses on the impact of pre-service teachers’ engagement in the annual BBC News School Report project on their emerging professional identity and on the evidence they provide as part of the process of becoming qualified. The research reported on is drawn from three years of enquiry. Respondents included pre-service teachers themselves, their tutors as representatives of teacher education providers and their mentors as representatives of schools in which they were placed. The methodological approach was interpretative and phenomenological with qualitative and quantitative data being analysed for emergent themes. Two years of evaluations were followed by a third year in which a set of case studies were developed. The research showed that professional identity is enhanced through being in a leading role in respect of curriculum and working with other staff. Through engagement in such projects, this paper moots that preservice teachers develop richer evidence of emerging professionalism as defined by standards of initial teacher training. Moreover, self-perception of role was modified to one in which they saw themselves, and were seen, as equals to qualified staff rather than subservient to or dependent on them. A new more equal power relationship developed as they took on responsibility for the project. Preservice teachers’ move to become full members of the professional community for which they are training was accelerated
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