Simulations of atmospheric methane for Cape Grim, Tasmania, to constrain southeastern Australian methane emissions

This study uses two climate models and six scenarios of prescribed methane emissions to compare modelled and observed atmospheric methane between 1994 and 2007, for Cape Grim, Australia (40.7° S, 144.7° E). The model simulations follow the TransCom-CH4 protocol and use the Australian Community Climate and Earth System Simulator (ACCESS) and the CSIRO Conformal-Cubic Atmospheric Model (CCAM). Radon is also simulated and used to reduce the impact of transport differences between the models and observations. Comparisons are made for air samples that have traversed the Australian continent. All six emission scenarios give modelled concentrations that are broadly consistent with those observed. There are three notable mismatches, however. Firstly, scenarios that incorporate interannually varying biomass burning emissions produce anomalously high methane concentrations at Cape Grim at times of large fire events in southeastern Australia, most likely due to the fire methane emissions being unrealistically input into the lowest model level. Secondly, scenarios with wetland methane emissions in the austral winter overestimate methane concentrations at Cape Grim during wintertime while scenarios without winter wetland emissions perform better. Finally, all scenarios fail to represent a~methane source in austral spring implied by the observations. It is possible that the timing of wetland emissions in the scenarios is incorrect with recent satellite measurements suggesting an austral spring (September–October–November), rather than winter, maximum for wetland emissions. © Author(s) 2015

Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures

Systematic review of safety checklists for use by medical care teams in acute hospital settings - limited evidence of effectiveness

<p>Abstract</p> <p>Background</p> <p>Patient safety is a fundamental component of good quality health care. Checklists have been proposed as a method of improving patient safety. This systematic review, asked "In acute hospital settings, would the use of safety checklists applied by medical care teams, compared to not using checklists, improve patient safety?"</p> <p>Methods</p> <p>We searched the Cochrane Library, MEDLINE, CINAHL, and EMBASE for randomised controlled trials published in English before September 2009. Studies were selected and appraised by two reviewers independently in consultation with colleagues, using inclusion, exclusion and appraisal criteria established a priori.</p> <p>Results</p> <p>Nine cohort studies with historical controls studies from four hospital care settings were included-intensive care unit, emergency department, surgery, and acute care. The studies used a variety of designs of safety checklists, and implemented them in different ways, however most incorporated an educational component to teach the staff how to use the checklist. The studies assessed outcomes occurring a few weeks to a maximum of 12 months post-implementation, and these outcomes were diverse.</p> <p>The studies were generally of low to moderate quality and of low levels of evidence, with all but one of the studies containing a high risk of bias.</p> <p>The results of these studies suggest some improvements in patient safety arising from use of safety checklists, but these were not consistent across all studies or for all outcomes. Some studies showed no difference in outcomes between checklist use and standard care without a checklist. Due to the variations in setting, checklist design, educational training given, and outcomes measured, it was unfeasible to accurately summarise any trends across all studies.</p> <p>Conclusions</p> <p>The included studies suggest some benefits of using safety checklists to improve protocol adherence and patient safety, but due to the risk of bias in these studies, their results should be interpreted with caution. More high quality and studies, are needed to enable confident conclusions about the effectiveness of safety checklists in acute hospital settings.</p

Nonthermal Emission from Star-Forming Galaxies

The detections of high-energy gamma-ray emission from the nearby starburst galaxies M82 & NGC253, and other local group galaxies, broaden our knowledge of star-driven nonthermal processes and phenomena in non-AGN star-forming galaxies. We review basic aspects of the related processes and their modeling in starburst galaxies. Since these processes involve both energetic electrons and protons accelerated by SN shocks, their respective radiative yields can be used to explore the SN-particle-radiation connection. Specifically, the relation between SN activity, energetic particles, and their radiative yields, is assessed through respective measures of the particle energy density in several star-forming galaxies. The deduced energy densities range from O(0.1) eV/cm^3 in very quiet environments to O(100) eV/cm^3 in regions with very high star-formation rates.Comment: 17 pages, 5 figures, to be published in Astrophysics and Space Science Proceeding

A cross-sectional study of the number and frequency of terms used to refer to knowledge translation in a body of health literature in 2006: a Tower of Babel?

<p/> <p>Background</p> <p>The study of implementing research findings into practice is rapidly growing and has acquired many competing names (<it>e.g</it>., dissemination, uptake, utilization, translation) and contributing disciplines. The use of multiple terms across disciplines pose barriers to communication and progress for applying research findings. We sought to establish an inventory of terms describing this field and how often authors use them in a collection of health literature published in 2006.</p> <p>Methods</p> <p>We refer to this field as knowledge translation (KT). Terms describing aspects of KT and their definitions were collected from literature, the internet, reports, textbooks, and contact with experts. We compiled a database of KT and other articles by reading 12 healthcare journals representing multiple disciplines. All articles published in these journals in 2006 were categorized as being KT or not. The KT articles (all KT) were further categorized, if possible, for whether they described KT projects or implementations (KT application articles), or presented the theoretical basis, models, tools, methods, or techniques of KT (KT theory articles). Accuracy was checked using duplicate reading. Custom designed software determined how often KT terms were used in the titles and abstracts of articles categorized as being KT.</p> <p>Results</p> <p>A total of 2,603 articles were assessed, and 581 were identified as KT articles. Of these, 201 described KT applications, and 153 included KT theory. Of the 100 KT terms collected, 46 were used by the authors in the titles or abstracts of articles categorized as being KT. For all 581 KT articles, eight terms or term variations used by authors were highly discriminating for separating KT and non-KT articles (p < 0.001): implementation, adoption, quality improvement, dissemination, complex intervention (with multiple endings), implementation (within three words of) research, and complex intervention. More KT terms were associated with KT application articles (n = 13) and KT theory articles (n = 18).</p> <p>Conclusions</p> <p>We collected 100 terms describing KT research. Authors used 46 of them in titles and abstracts of KT articles. Of these, approximately half discriminated between KT and non-KT articles. Thus, the need for consolidation and consistent use of fewer terms related to KT research is evident.</p

Leptin Activates Anorexigenic POMC Neurons through a Neural Network in the Arcuate Nucleus

The administration of leptin to leptin-deficient humans, and the analogous Lepob/Lepob mice, effectively reduces hyperphagia and obesity. But common obesity is associated with elevated leptin, which suggests that obese humans are resistant to this adipocyte hormone. In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activity. Proopiomelanocortin (POMC) and neuropeptide-Y types of neurons in the arcuate nucleus of the hypothalamus7 are both principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins and neuropeptide Y, which exert opposing effects on feeding and metabolism. These neurons are therefore ideal for characterizing leptin action and the mechanism of leptin resistance; however, their diffuse distribution makes them difficult to study. Here we report electrophysiological recordings on POMC neurons, which we identified by targeted expression of green fluorescent protein in transgenic mice. Leptin increases the frequency of action potentials in the anorexigenic POMC neurons by two mechanisms: depolarization through a nonspecific cation channel; and reduced inhibition by local orexigenic neuropeptide-Y/GABA (g-aminobutyric acid) neurons. Furthermore, we show that melanocortin peptides have an autoinhibitory effect on this circuit. On the basis of our results, we propose an integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamu

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)