561 research outputs found
Evaluation of âStop Smoking in its Tracksâ
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
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
Analysis of multiply substituted isotopologues of
molecules (âclumped isotope geochemistryâ) 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 (Î_(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 Î_(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 Î_(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 Î_(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 Î_(47) values to within est.
±0.01 â°, 1Ï. 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 âclumped
isotopeâ measurements
High-temperature environments of human evolution in East Africa based on bond ordering in paleosol carbonates
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, Kenyaâtoday one of the hottest places on Earthâhas 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
Transient mantle cooling linked to regional volcanic shut-down and early rifting in the North Atlantic Igneous Province
Open Access via the Springer Compact AgreementPeer reviewedPublisher PD
Smoke-free homes: what are the barriers, motivators and enablers? A qualitative systematic review and thematic synthesis
Objective: To thematically synthesise primary qualitative studies of the barriers, motivators and enablers of smoke-free homes (SFHs).
Design: Systematic review and thematic synthesis.
Data sources: Searches of MEDLINE, EBM Reviews (Cochrane Database of Systematic Reviews), PsycINFO, Global Health, CINAHL, Web of Science, Informit and EMBASE, combining terms for families, households and vulnerable populations; SFH and secondhand smoke; and qualitative research, were supplemented by searches of PhD theses, key authors, specialist journals and reference lists.
Study selection: We included 22 articles, reporting on 18 studies, involving 646 participants. Inclusion criteria: peer-reviewed; English language; published from 1990 onwards (to week 3 of April 2014); used qualitative data collection methods; explored participantsâ perspectives of home smoking behaviours; and the barriers, motivators and enablers to initiating and/or maintaining a SFH.
Data extraction: 1 of 3 authors extracted data with checking by a second.
Data synthesis: A thematic synthesis was performed to develop 7 core analytic themes: (1) knowledge, awareness and risk perception; (2) agency and personal skills/attributes; (3) wider community norms and personal moral responsibilities; (4) social relationships and influence of others; (5) perceived benefits, preferences and priorities; (6) addiction and habit; (7) practicalities.
Conclusions: This synthesis highlights the complexity faced by many households in having a SFH, the practical, social, cultural and personal issues that need to be addressed and balanced by households, and that while some of these are common across study settings, specific social and cultural factors play a critical role in shaping household smoking behaviours. The findings can inform policy and practice and the development of interventions aimed at increasing SFHs.
Trial registration number: CRD42014014115
Getting the Message Across for Safer Self-Recovery in Post-Disaster Shelter
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
Issue addressed: Australiansâ 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 â smoking tobacco and cannabis together â using a grounded theory approach. Methods: Twenty-one in-depth semi structured interviews were conducted with men aged 25â34 and living on the North Coast of New South Wales. Interviews explored participantsâ 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 â 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 45â64 years from 2015 to 2030:Results from a microsimulation model
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 45â64 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 45â64â
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 380â
000 (6.4%) people aged 45â64â
years with lost PLYs in 2015, increasing to 462â
000 (6.5%) in 2030âa 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 A20.5 billion in 2030âa 62.7% increase. Additional costs to the government consisted of increased welfare payments at A7.3 billion in 2030âa 17.7% increase; and a loss of A4.7 billion in 2030âa growth of 51.6%.
Conclusions: There is a need for greater investment in effective preventive health interventions which improve workersâ health and work capacity.Full Tex
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Population differentiation of the apple scab fungus Venturia inaequalis on cultivars within a mixed cultivar orchard
Apple cultivars differ in their resistance to the fungal pathogen Venturia inaequalis, the causal agent of apple scab. Mixed cultivar orchards, where the cultivars present have differing resistance to V. inaequalis, have been shown to reduce the levels of scab compared to monoculture. To maximise the mixture effect on reducing scab development, cultivars need to be selected with maximum differences in their scab resistance. One indirect, yet efficient, method of selecting such cultivars is to quantify population differences of scab from different cultivars, which are expected to largely reflect the differences in the resistance to the pathogen.
We sampled early season scab lesions from different cultivars in two mixed cider cultivar orchards in the
Southwest of England and from various desert and cider cultivars in an orchard in the Southeast of England. Using Simple Sequence Repeat (SSR) markers we compared the scab populations sampled from the different cultivars. Scab populations from different cultivars differed significantly, depend ng on specific pairs of cultivars; however, larger differences appear to be among fungal populations from different sites. The results demonstrate that certain cultivars likely share much of their genetic resistance factors to V. inaequalis.
For dessert apple the scab populations on Cox, Gala, Bramley and Fiesta were not different and therefore it is not advisable to plant these cultivars in the same orchard with a view to reducing scab development. On the other hand, a reduction in scab would be more likely if one of the above cultivars were planted together with Golden Delicious, Red Falstaff or Spartan.
There was a very large difference in the scab population from cv. Three Counties and populations from all other cider cultivars. This was particularly surprising given the shared parentage (Dabinett x James Greave) between Three Counties and all but one of the other cider cultivars sampled, suggesting considerable differences in the resistance to V. inaequalis between the two parents. It also indicates that selection of cultivars for inclusion in mixed orchards cannot be reliably made based on pedigree information alone
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