The Sun, stellar-population models, and the age estimation of high-redshift galaxies

Given sufficiently deep optical spectroscopy, the age estimation of high-redshif t ($z > 1$) galaxies has been claimed to be a relatively robust process (e.g. Dunlop et al. 1996) due to the fact that, for ages $< 5$Gyr, the near-ultraviolet light of a stellar population is expected to be dominated by `well-understood' main-sequence (MS) stars. Recently, however, the reliability of this process has been called into question by Yi et al (2000), who claim to have developed models in which the spectrum produced by the main sequence reddens much more rapidly than in the models of Jimenez et al (2000a), leading to much younger age estimates for the reddest known high-redshift ellipticals. In support of their revised age estimates, Yi et al cite the fact that their models can reproduce the spectrum of the Sun at an age of 5 Gyr, whereas the solar spectrum is not reproduced by the Jimenez et al models until $\simeq 10$ Gyr. Here we confirm this discrepancy, but point out that this is in fact a {\it strength} of the Jimenez et al models and indicative of some flaw in the models of Yi et al (which, in effect, imply that the Sun will turn into a red giant any minute now). We have also explored the models of Worthey (1994) (which are known to differ greatly from those of Jimenez et al in the treatment of post-MS evolution) and find that the main-sequence component of Worthey's models also cannot reproduce the solar spectrum until an age of 9-10 Gyr. We conclude that either the models of Yi et al are not as main-sequence dominated at 4-5 Gyr as claimed, or that the stellar evolutionary timescale in these models is in error by a factor possibly as high as two. (abridged)Comment: Submitted to MNRAS, final versio

Subsidization of the Biofuel Industry: Security vs. Clean Air?

Replaced with revised version of paper 07/11/06.Resource /Energy Economics and Policy,

The ages of quasar host galaxies

We present the results of fitting deep off-nuclear optical spectroscopy of radio-quiet quasars, radio-loud quasars and radio galaxies at z ~ 0.2 with evolutionary synthesis models of galaxy evolution. Our aim was to determine the age of the dynamically dominant stellar populations in the hos t galaxies of these three classes of powerful AGN. Some of our spectra display residual nuclear contamination at the shortest wavelengths, but the detailed quality of the fits longward of the 4000A break provide unequivocal proof, if further proof were needed, that quasars lie in massive galaxies with (at least at z ~ 0.2) evolved stellar populations. By fitting a two-component model we have separated the very blue (starburst and/or AGN contamination) from the redder underlying spectral energy distribution, and find that the hosts of all three classes of AGN are dominated by old stars of age 8 - 14 Gyr. If the blue component is attributed to young stars, we find that, at most, 1% of the baryonic mass of these galaxies is involved in star-formation activity at the epoch of observation. These results strongly support the conclusion reached by McLure et al. (1999) that the host galaxies of luminous quasars are massive ellipticals which formed prior to the peak epoch of quasar activity at z ~ 2.5.Comment: 24 pages, LaTeX, uses MNRAS style file, incorporates 19 postscript figures, final version, to be published in MNRA

The relevance of bacterial isoprenoid biosynthetic pathways for host-microbe interactions

This thesis was undertaken to investigate the relevance of two bacterial isoprenoid biosynthetic pathways (Mevalonate (MVAL) and 2-C-methyl-D-erythritol 4-phosphate (MEP)) for host-microbe interactions. We determined a significant reduction in microbial diversity in the murine gut microbiota (by next generation sequencing) following oral administration of a common anti-cholesterol drug Rosuvastatin (RSV) that targets mammalian and bacterial HMG-CoA reductase (HMG-R) for inhibition of MVAL formation. In tandem we identified significant hepatic and intestinal off-target alterations to the murine metabolome indicating alterations in inflammation, bile acid profiles and antimicrobial peptide synthesis with implications on community structure of the gastrointestinal microbiota in statin-treated animals. However we found no effect on local Short Chain Fatty Acid biosynthesis (metabolic health marker in our model). We demonstrated direct inhibition of bacterial growth in-vitro by RSV which correlated with reductions in bacterial MVAL formation. However this was only at high doses of RSV. Our observations demonstrate a significant RSV-associated impact on the gut microbiota prompting similar human analysis. Successful deletion of another MVAL pathway enzyme (HMG-CoA synthase (mvaS)) involved in Listeria monocytogenes EGDe isoprenoid biosynthesis determined that the enzyme is non-essential for normal growth and in-vivo pathogenesis of this pathogen. We highlight potential evidence for alternative means of synthesis of the HMG-CoA substrate that could render mvaS activity redundant under our test conditions. Finally, we showed by global gene expression analysis (Massive Analysis of cDNA Ends (MACE RNA-seq) a significant role for the penultimate MEP pathway metabolite (E)-4-hydroxy-3-methyl-2-but-2-enyl pyrophosphate (HMBPP) in significant up regulation of genes of immunity and antigen presentation in THP-1 cells at nanomolar levels. We infected THP-1 cells with wild type or HMBPP under/over-producing L. monoctyogenes EGDe mutants and determined subtle effects of HMBPP upon overall host responses to Listeria infection. Overall our findings provide greater insights regarding bacterial isoprenoid biosynthetic pathways for host-microbe/microbe-host dialogue

Checks and cheques : implementing a population health and recall system to improve coverage of patients with diabetes in a rural general practice

Identification of all diabetic patients in the population is essential if diabetic care is to be effective in achieving the targets of the St Vincent Declaration.1 The challenge therefore is to establish population based monitoring and control systems by means of state of the art technology in order to achieve quality assurance in the provision of care for patients with diabetes. 2,3 Disease management receives extensive international support as the most appropriate approach to organising and delivering healthcare for chronic conditions like diabetes.4 This approach is achieved through a combination of guidelines for practice, patient education, consultations and follow up using a planned team approach and a strong focus on continuous quality improvement using information technology. 5,6 The current software (Medical Director) could not easily meet these requirements which led us to adopt a trial of Ferret. In designing this project we used change management7 and the plan, do, study, act cycle8 illustrated in Diagram 1.<br /

Microsphere cytometry to interrogate microenvironment-dependent cell signaling

Microenvironmental cues comprising surface-mediated and soluble factors control cellular signaling mechanisms underlying normal cellular responses that define homeostatic and diseased cell states. In order to measure cell signaling in single adherent cells, we developed a novel microsphere-based flow cytometry approach. Single normal or neoplastic cells were adhered to uniform microspheres that display mimetic-microenvironments comprising surface combinations of extracellular matrix (ECM) in the presence of soluble agonists/antagonists. Temporal signaling responses were measured with fluorophore-conjugated antibodies that recognize response-dependent epitopes by multiparametric flow cytometry. Using this approach we demonstrate that microenvironment-mimetic combinations of growth factors and extracellular matrix proteins generate distinct cellular signal networks that reveal unique cell signatures in normal and patient biopsy-derived neoplastic cells.acceptedVersio

Access and non–access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events:Systematic review and meta-analysis

Background: The prognostic impact of site-specific major bleeding complications after percutaneous coronary intervention (PCI) has yielded conflicting data. The aim of this study is to provide an overview of site-specific major bleeding events in contemporary PCI and study their impact on mortality and major adverse cardiovascular event outcomes. Methods and Results: We conducted a meta-analysis of PCI studies that evaluated site-specific periprocedural bleeding complications and their impact on major adverse cardiovascular events and mortality outcomes. A systematic search of MEDLINE and Embase was conducted to identify relevant studies and random effects meta-analysis was used to estimate the risk of adverse outcomes with site-specific bleeding complications. Twenty-five relevant studies including 2 400 645 patients that underwent PCI were identified. Both non–access site (risk ratio [RR], 4.06; 95% confidence interval [CI], 3.21–5.14) and access site (RR, 1.71; 95% CI, 1.37–2.13) related bleeding complications were independently associated with an increased risk of periprocedural mortality. The prognostic impact of non–access site–related bleeding events on mortality related to the source of anatomic bleeding, for example, gastrointestinal RR, 2.78; 95% CI, 1.25 to 6.18; retroperitoneal RR, 5.87; 95% CI, 1.63 to 21.12; and intracranial RR, 22.71; 95% CI, 12.53 to 41.15. Conclusions: The prognostic impact of bleeding complications after PCI varies according to anatomic source and severity. Non–access site-related bleeding complications have a similar prevalence to those from the access site but are associated with a significantly worse prognosis partly related to the severity of the bleed. Clinicians should minimize the risk of major bleeding complications during PCI through judicious use of bleeding avoidance strategies irrespective of the access site used

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation

Clinical Significance of Manuka and Medical-Grade Honey for Antibiotic-Resistant Infections: A Systematic Review

Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the “golden age” of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important than ever. Honey has been used as a topical wound treatment for millennia and more recently has been formulated into a series of medical-grade honeys for use primarily for wound and burn treatment. In this systematic review, we examined the effectiveness of differing honeys as an antimicrobial treatment against a variety of multidrug-resistant (MDR) bacterial species. We analysed 16 original research articles that included a total of 18 different types of honey against 32 different bacterial species, including numerous MDR strains. We identified that Surgihoney was the most effective honey, displaying minimum inhibitory concentrations as low as 0.1% (w/v); however, all honeys reviewed showed a high efficacy against most bacterial species analysed. Importantly, the MDR status of each bacterial strain had no impact on the susceptibility of the organism to honey. Hence, the use of honey as an antimicrobial therapy should be considered as an alternative approach for the treatment of antibiotic-resistant infections

Fall hazard control observed on residential construction sites

BACKGROUND: Falls are a leading cause of mortality and morbidity in the construction industry. This study measured fall hazards at residential construction sites. METHODS: Trained carpenters administered the St. Louis Audit of Fall Risks and interviewed carpenters. The prevalence of fall prevention practices meeting safety criteria was counted and correlations explored. RESULTS: We identified a high prevalence of fall hazards at the 197 residential sites audited. Roof sheathing met safety criteria most consistently (81%) and truss setting least consistently (28%). Use of personal fall arrest and monitoring of unguarded floor openings were rare. Safer performance on several scales was correlated. Construction sites of large-sized contractors were generally safer than smaller contractors. Apprentice carpenters were less familiar with their employers’ fall prevention plan than experienced workers. CONCLUSIONS: Safety could be improved with consistent use of recognized fall prevention practices at residential construction sites