Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis

Background: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered. Objective: To extend earlier meta-analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships. Methods: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (Crl)) as a function of the additional time delay associated with angioplasty. \ Results: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean ( SE) angioplasty-related time delay ( over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis ( OR = 0.68 ( 95% Crl 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 ( 95% Crl 0.20 to 0.51); for non-fatal stroke OR = 0.24 ( 95% Crl 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation. Conclusions: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1- month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays

Aspects of Sporinite Chemistry

With the recent advent of the ability to separate coal into maceral concentrates of high purity, the individual constituents of coal can now be analyzed separately, without their mutual interference, giving a much better understanding of the macromolecular structure of coal. The sporinites from two Pennsylvanian age coal samples (Illinois Basin, U.S.A.) were studied, one from a vitrinite-rich high-volatile bituminous coal, the other from a liptinite-rich high-volatile bituminous coal of slightly higher rank. Sporinites were isolated from each coal by density gradient centrifugation. The sporinite of the vitrinite-rich coal was compared chemically and petrographically with the parent coal and with the sporinite of the liptinite-rich coal. The fluorescence spectrum of the sporinite from the liptinite-rich coal is shifted to the red end of the spectrum, which may be accounted for by the somewhat higher rank of the sample and/or by differences in the original assemblage of spores. The lack of chemical differences between the extracts of the sporinite and its whole coal reinforce the concept of bitumen as an homogeneous mobile phase pervading the coal. Thus, extract chemistry seems an unsuitable technique for distinguishing between macerals from the same coal. Hopane and sterane distributions in the sporinite and parent coal pyrolyzates are very similar, but the two materials can be readily distinguished by the distribution of tetracyclic diterpanes of the phyllocladane type, which are biological marker compounds derived from higher plant material. Overall, the sporinite is considerably more paraffinic in character and has a greater preponderance of straight-chain alkane moieties than the coal as a whole. In the case of the vitrinite-rich coal, the whole-coal structure appears significantly more polyaromatic than the sporinite. The distributions of thiophenic compounds differ in the pyrolyzates of the two materials. The sporinite from the liptinite-rich coal is even less polycondensed than the sporinite from the vitrinite-rich sample. The chemical and petrographic differences of the two sporinites probably reflect the different assemblages of spores in the original peats and their different diagenetic histories

Characterization of Organic Sulfur Compounds in Coals and Coal Macerals

Peroxyacetic acid oxidation has been used to investigate the type and distribution of organic sulfur species in samples of vitrinite, sporinite and inertinite, separated from the Herrin No.6 and an Indiana No.5 coal seam. It was established that organic sulfur species were selectively preserved during oxidation and their analysis led to some of the first sulfur-33 NMR spectra obtained for coal. The effects of maceral separation processes on model compounds were also studied. Results from our studies support the following conclusions: 1). Different macerals have different distributions and types of organic sulfur species. 2). Organic sulfur compounds in coal occur at the ends of macromolecular structures. 3). Maceral separation techniques do not affect organic sulfur species in coal. 4). Maceral separation is essential for the chemical characterization of coal. 5). GC-MS and sulfur-33 NMR data agree

Mapping the Galactic Halo. V. Sgr dSph Tidal Debris 60 degrees from the Main Body

As part of the Spaghetti Project Survey (SPS) we have detected a concentration of giant stars well above expectations for a smooth halo model. The position (l~350, b~50) and distance (~50 kpc) of this concentration match those of the Northern over-density detected by SDSS (Yanny et al. 2000, Ivezic et al. 2000). We find additional evidence for structure at ~80 kpc in the same direction. We present radial velocities for many of these stars, including the first published results from the 6.5m Magellan telescope. The radial velocities for stars in these structures are in excellent agreement with models of the dynamical evolution of the Sgr dwarf tidal debris, whose center is 60 degrees away. The metallicity of stars in these streams is lower than that of the main body of the Sgr dwarf, which may indicate a radial metallicity gradient prior to disruption.Comment: 10 pages, 3 figures accepted in Astrophysical Journal Letter

Improving reintroduction success in large carnivores through individual-based modelling: How to reintroduce Eurasian lynx (Lynx lynx) to Scotland

Globally, large carnivores have been heavily affected by habitat loss, fragmentation and persecution, sometimes resulting in local extinctions. With increasing recognition of top-down trophic cascades and complex predator- prey dynamics, reintroductions are of growing interest for restoration of ecosystem functioning. Many re- introductions have however failed, in part due to poor planning and inability to model complex eco-evolutionary processes to give reliable predictions. Using the case study of Eurasian lynx (Lynx lynx), a large predator being considered for reintroduction to Scotland, we demonstrate how an individual-based model that integrates demography with three distinct phases of dispersal (emigration, transfer and settlement) can be used to explore the relative suitability of three geographically-distant potential reintroduction sites, multi-site reintroductions and two founding population sizes. For a single-site reintroduction of 10 lynx, our simulation results show a clear hierarchy of suitability across all metrics. Reintroduction in the Kintyre Peninsula (west coast) consistently performed best, with a probability of population persistence at year 100 of 83%, and the Scottish component of Kielder Forest (southern Scotland) worst, with only a 21% chance of population persistence to year 100. Simultaneous two-site reintroduction in the Kintyre Peninsula and in Aberdeenshire (near the east coast) of 32 lynx gave a 96% persistence at 100 years. Our model was highly sensitive to survival, particularly of adults, highlighting this parameter's importance for reintroduction success. The results strongly indicate the potential viability of Eurasian lynx reintroduction to Scotland given the current cover of suitable woodland habitat. More generally, our work demonstrates how emerging modelling approaches incorporating increased realism in re- presenting species' demography, ecology and dispersal can have high value for quick, inexpensive assessment of likely reintroduction success and for selection between alternative strategies.REF Compliant by Deposit in Stirling's Repositor

Genetic variation in the SIM1 locus is associated with erectile dysfunction.

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function

Benzo-fused Lactams from a Diversity-oriented Synthesis (DOS) Library as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

We report a new series of 8-membered benzo-fused lactams that inhibit cellular lipid uptake from HDL particles mediated by Scavenger Receptor, Class B, Type I (SR-BI). The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR), measuring the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is part of a previously reported diversity-oriented synthesis (DOS) library prepared via a build-couple-pair approach. Detailed structure–activity relationship (SAR) studies were performed with a selection of the original library, as well as additional analogs prepared via solution phase synthesis. These studies demonstrate that the orientation of the substituents on the aliphatic ring have a critical effect on activity. Additionally, a lipophilic group is required at the western end of the molecule, and a northern hydroxyl group and a southern sulfonamide substituent also proved to be optimal. Compound 2p was found to possess a superior combination of potency (av IC50 = 0.10 μM) and solubility (79 μM in PBS), and it was designated as probe ML312

Matched-Cohort Analysis of Autologous Hematopoietic Cell Transplantation with Radioimmunotherapy versus Total Body Irradiation–Based Conditioning for Poor-Risk Diffuse Large Cell Lymphoma

We conducted a matched-cohort analysis of autologous transplant conditioning regimens for diffuse large cell lymphoma in 92 patients treated with either radioimmunotherapy (RIT) or total body irradiation (TBI)–based conditioning regimens. The RIT regimen consisted of 0.4 mCi/kg of 90Y-ibritumomab tiuxetan plus BEAM (BCNU, etoposide, cytarabine, melphalan). The TBI-based regimen combined fractionated TBI at 1200 cGy, with etoposide and cyclophosphamide. Five factors were matched between 46 patient pairs: age at transplant ±5 years, disease status at salvage, number of prior regimens, year of diagnosis ±5 years, and year of transplantation ±5 years. Patients in the TBI group had higher rates of cardiac toxicity and mucositis, whereas Z-BEAM patients had a higher incidence of pulmonary toxicity. Overall survival at 4 years was 81.0% for the Z-BEAM and 52.7% for the TBI group (P = .01). The 4-year cumulative incidence of relapse/progression was 40.4% and 42.1% for Z-BEAM and TBI, respectively (P = .63). Nonrelapse mortality was superior in the Z-BEAM group: 0% compared with 15.8% for TBI at 4 years (P < .01). Our data demonstrate that RIT-based conditioning had a similar relapse incidence to TBI, with lower toxicity, resulting in improved overall survival, particularly in patients with ≥2 prior regimens