The incidence of all-cause, cardiovascular and respiratory disease admission among 20,252 users of lisinopril vs. perindopril: a cohort study

Background: Major international guidelines do not offer explicit recommendations on any specific angiotensin-converting enzyme inhibitor (ACEI) agent over another within the same drug group. This study compared the effectiveness of lisinopril vs. perindopril in reducing the incidence of hospital admission due to all-cause, cardiovascular disease and respiratory disease. Methods: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for ≥2 years. The incidence of admissions due to all-cause, cardiovascular disease and respiratory disease were evaluated, respectively, by using Cox proportional hazard regression models. The regression models were constructed with propensity score matching to minimize indication biases. Results: A total of 20,252 eligible patients with an average age of 64.5 years (standard deviation 15.0) were included. The admission rate at 24 months within the date of index prescription due to any cause, cardiovascular disease and respiratory disease among lisinopril vs. perindopril users was 24.8% vs. 24.8%, 13.7% vs. 14.0% and 6.9% vs. 6.3%, respectively. Lisinopril users were significantly more likely to be admitted due to respiratory diseases (adjusted hazard ratios [AHR] = 1.25, 95% CI 1.08 to 1.43, p = 0.002 at 12 months; AHR = 1.17, 95% CI 1.04 to 1.31, p = 0.009 at 24 months) and all causes (AHR = 1.12, 95% CI 1.05 to 1.19, p < 0.001 at 24 months) than perindopril users. Conclusions: These findings support intra-class differences in the effectiveness of ACEIs, which could be considered by clinical guidelines when the preferred first-line antihypertensive drugs are recommended

Contributions of individual reactive biogenic volatile organic compounds to organic nitrates above a mixed forest

Biogenic volatile organic compounds (BVOCs) can react in the atmosphere to form organic nitrates, which serve as $\text{NO}_{x} (\text{NO} + \text{NO}_{2})$ reservoirs, impacting ozone and secondary organic aerosol production, the oxidative capacity of the atmosphere, and nitrogen availability to ecosystems. To examine the contributions of biogenic emissions and the formation and fate of organic nitrates in a forest environment, we simulated the oxidation of 57 individual BVOCs emitted from a rural mixed forest in northern Michigan. Key BVOC-oxidant reactions were identified for future laboratory and field investigations into reaction rate constants, yields, and speciation of oxidation products. Of the total simulated organic nitrates, monoterpenes contributed ~70% in the early morning at ~12 m above the forest canopy when isoprene emissions were low. In the afternoon, when vertical mixing and isoprene nitrate production were highest, the simulated contribution of isoprene-derived organic nitrates was greater than 90% at all altitudes, with the concentration of secondary isoprene nitrates increasing with altitude. Notably, reaction of isoprene with $\text{NO}_{3}$ leading to isoprene nitrate formation was found to be significant (~8% of primary organic nitrate production) during the daytime, and monoterpene reactions with $\text{NO}_{3}$ were simulated to comprise up to ~83% of primary organic nitrate production at night. Lastly, forest succession, wherein aspen trees are being replaced by pine and maple trees, was predicted to lead to increased afternoon concentrations of monoterpene-derived organic nitrates. This further underscores the need to understand the formation and fate of these species, which have different chemical pathways and oxidation products compared to isoprene-derived organic nitrates and can lead to secondary organic aerosol formation

Simulation techniques for cosmological simulations

Modern cosmological observations allow us to study in great detail the evolution and history of the large scale structure hierarchy. The fundamental problem of accurate constraints on the cosmological parameters, within a given cosmological model, requires precise modelling of the observed structure. In this paper we briefly review the current most effective techniques of large scale structure simulations, emphasising both their advantages and shortcomings. Starting with basics of the direct N-body simulations appropriate to modelling cold dark matter evolution, we then discuss the direct-sum technique GRAPE, particle-mesh (PM) and hybrid methods, combining the PM and the tree algorithms. Simulations of baryonic matter in the Universe often use hydrodynamic codes based on both particle methods that discretise mass, and grid-based methods. We briefly describe Eulerian grid methods, and also some variants of Lagrangian smoothed particle hydrodynamics (SPH) methods.Comment: 42 pages, 16 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 12; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Hypoxia, not pulmonary vascular pressure induces blood flow through intrapulmonary arteriovenous anastomoses

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times-a-day for 48 h) to prevent increases in PASP, and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ+HCO3-) to control for AZ-induced acidosis. Isocapnic hypoxia (20 min) was maintained by end-tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic-hypoxia condition to determine pH, [HCO3-], and PaCO2. AZ decreased pH (-0.08 ± 0.01), [HCO3-] (-7.1 ± 0.7 mmol/l), and PaCO2 (-4.5 ± 1.4 mmHg; p<0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (p<0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (p<0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (p<0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H+ concentration or PaCO2. Abbreviations list: AZ, acetazolamide; FEV1, forced expiratory volume in 1 second; FIO2, fraction of inspired oxygen; FVC, forced vital capacity; Hb, total haemoglobin; HPV, hypoxic pulmonary vasoconstriction; HR, heart rate; IPAVA, intrapulmonary arteriovenous anastomoses; MAP, mean arterial pressure; PASP, pulmonary artery systolic pressure; PETCO2, end-tidal partial pressure of carbon dioxide; PETO2, end-tidal partial pressure of oxygen; PFO, patent foramen ovale; PVR, pulmonary vascular resistance; Q̇c, cardiac output; RVOT, right ventricular outflow tract; SpO2, oxyhaemoglobin saturation; SV, stroke volume; TRV, tricuspid regurgitant velocity; V̇E, minute ventilation; VTI, velocity-time integra

Cosmology with clusters of galaxies

In this Chapter I review the role that galaxy clusters play as tools to constrain cosmological parameters. I will concentrate mostly on the application of the mass function of galaxy clusters, while other methods, such as that based on the baryon fraction, are covered by other Chapters of the book. Since most of the cosmological applications of galaxy clusters rely on precise measurements of their masses, a substantial part of my Lectures concentrates on the different methods that have been applied so far to weight galaxy clusters. I provide in Section 2 a short introduction to the basics of cosmic structure formation. In Section 3 I describe the Press--Schechter (PS) formalism to derive the cosmological mass function, then discussing extensions of the PS approach and the most recent calibrations from N--body simulations. In Section 4 I review the methods to build samples of galaxy clusters at different wavelengths. Section 5 is devoted to the discussion of different methods to derive cluster masses. In Section 6 I describe the cosmological constraints, which have been obtained so far by tracing the cluster mass function with a variety of methods. Finally, I describe in Section 7 the future perspectives for cosmology with galaxy clusters and the challenges for clusters to keep playing an important role in the era of precision cosmology.Comment: 49 pages, 19 figures, Lectures for 2005 Guillermo Haro Summer School on Clusters, to appear in "Lecture notes in Physics" (Springer

Clusters of galaxies: setting the stage

Clusters of galaxies are self-gravitating systems of mass ~10^14-10^15 Msun. They consist of dark matter (~80 %), hot diffuse intracluster plasma (< 20 %) and a small fraction of stars, dust, and cold gas, mostly locked in galaxies. In most clusters, scaling relations between their properties testify that the cluster components are in approximate dynamical equilibrium within the cluster gravitational potential well. However, spatially inhomogeneous thermal and non-thermal emission of the intracluster medium (ICM), observed in some clusters in the X-ray and radio bands, and the kinematic and morphological segregation of galaxies are a signature of non-gravitational processes, ongoing cluster merging and interactions. In the current bottom-up scenario for the formation of cosmic structure, clusters are the most massive nodes of the filamentary large-scale structure of the cosmic web and form by anisotropic and episodic accretion of mass. In this model of the universe dominated by cold dark matter, at the present time most baryons are expected to be in a diffuse component rather than in stars and galaxies; moreover, ~50 % of this diffuse component has temperature ~0.01-1 keV and permeates the filamentary distribution of the dark matter. The temperature of this Warm-Hot Intergalactic Medium (WHIM) increases with the local density and its search in the outer regions of clusters and lower density regions has been the quest of much recent observational effort. Over the last thirty years, an impressive coherent picture of the formation and evolution of cosmic structures has emerged from the intense interplay between observations, theory and numerical experiments. Future efforts will continue to test whether this picture keeps being valid, needs corrections or suffers dramatic failures in its predictive power.Comment: 20 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 2; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe