Variations in water economy traits in two Sphagnum species across their distribution boundaries.

PREMISE: We assessed changes in traits associated with water economy across climatic gradients in the ecologically similar peat mosses Sphagnum cuspidatum and Sphagnum lindbergii. These species have parapatric distributions in Europe and have similar niches in bogs. Sphagnum species of bogs are closely related, with a large degree of microhabitat niche overlap between many species that can be functionally very similar. Despite this, ecologically similar species do have different distributional ranges along climatic gradients that partly overlap. These gradients may favor particular Sphagnum traits, especially in relation to water economy, which can be hypothesized to drive species divergence by character displacement. METHODS: We investigated traits relevant for water economy of two parapatric bryophytes (Sphagnum cuspidatum and S. lindbergii) across the border of their distributional limits. We included both shoot traits and canopy traits, i.e., collective traits of the moss surface, quantified by photogrammetry. RESULTS: The two species are ecologically similar and occur at similar positions along the hydrological gradient in bogs. The biggest differences between the species were expressed in the variations of their canopy surfaces, particularly surface roughness and in the responses of important traits such as capitulum mass to climate. We did not find support for character displacement, because traits were not more dissimilar in sympatric than in allopatric populations. CONCLUSIONS: Our results suggest that parapatry within Sphagnum can be understood from just a few climatic variables and that climatic factors are stronger drivers than competition behind trait variation within these species of Sphagnum.

Velocity-resolved kinetics of site-specific carbon monoxide oxidation on platinum surfaces.

Catalysts are widely used to increase reaction rates. They function by stabilizing the transition state of the reaction at their active site, where the atomic arrangement ensures favourable interactions 1 . However, mechanistic understanding is often limited when catalysts possess multiple active sites-such as sites associated with either the step edges or the close-packed terraces of inorganic nanoparticles2-4-with distinct activities that cannot be measured simultaneously. An example is the oxidation of carbon monoxide over platinum surfaces, one of the oldest and best studied heterogeneous reactions. In 1824, this reaction was recognized to be crucial for the function of the Davy safety lamp, and today it is used to optimize combustion, hydrogen production and fuel-cell operation5,6. The carbon dioxide products are formed in a bimodal kinetic energy distribution7-13; however, despite extensive study 5 , it remains unclear whether this reflects the involvement of more than one reaction mechanism occurring at multiple active sites12,13. Here we show that the reaction rates at different active sites can be measured simultaneously, using molecular beams to controllably introduce reactants and slice ion imaging14,15 to map the velocity vectors of the product molecules, which reflect the symmetry and the orientation of the active site 16 . We use this velocity-resolved kinetics approach to map the oxidation rates of carbon monoxide at step edges and terrace sites on platinum surfaces, and find that the reaction proceeds through two distinct channels11-13: it is dominated at low temperatures by the more active step sites, and at high temperatures by the more abundant terrace sites. We expect our approach to be applicable to a wide range of heterogeneous reactions and to provide improved mechanistic understanding of the contribution of different active sites, which should be useful in the design of improved catalysts.

A method to determine the retinal radiant exposure caused by ophthalmoscopy.

PURPOSE: To introduce a method to calculate retinal irradiance caused by ophthalmoscopy. This may be used to verify the compliance of an instrument with the radiation limits set by light hazard standards. The proposed method is simpler to use and less prone to error than the methods currently found in the light hazard standards. METHODS: The optical properties of the standardised human eye, specified by current light hazard standards, are used to calculate the magnification of an aerial image of the retinal surface by the combination of the optics of eye and the auxiliary lens used for ophthalmoscopy. The magnification of the aerial image is used to transform the spectral irradiance of the instrument illumination source to retinal irradiation values. The spectral irradiance of the instrument illumination source can be measured directly as the aerial image is located in the focal plane of the viewing optics of the ophthalmoscope. These spectral irradiation values are then processed using weightings specified by current light hazard standards to give a weighted irradiance which is converted directly to a retinal irradiance value. RESULTS: A single formula is provided to calculate the retinal irradiance using the processed, measured spectral irradiance values of the illumination source. CONCLUSION: The new method introduced here is simpler to use, requires fewer physical measurements and is less likely to introduce measurement error than that currently found in light hazard standards. The only physical measurement that needs to be taken is the illumination source spectral irradiance measured in the viewing focal plane of the instrument. These values are weighted using given in the light hazard standards. The combined irradiance value is then converted to retinal irradiance using the formula given in this paper.

The use of autorefractors using the image-size principle in determining on-axis and off-axis refraction. Part 1: Analysis of optical principles of autorefractors.

PURPOSE: To study the optical principles and properties of autorefractors that use the image-size principle in which the size of the reimaged retinal image determines refraction. METHODS: The retinal illumination and reimaging of the retinal image were described, as were variations in the basic system. Imaging was determined for systems in which the light source is either diverging or converging as it passes into the eye. Equations were determined to describe the dependence of refraction on the heights and angles of incoming and outgoing beams, and refraction error was determined when eye position was not correct. RESULTS: The fundamental refraction equation is DE=±(α+θ)/h1 where DE is refraction, h1 is the beam height entering the eye, and θ and α are the angles of the incoming and outgoing beams, respectively. The negative sign outside the brackets applies if the beam focuses before entering the eye, while the positive sign applies if the beam focuses after entering the eye. When light is diverging as it reaches the anterior eye, hyperopia produces greater retinal image sizes than myopia. The opposite is the case when light is converging as it reaches the anterior eye. The effect of incorrect ocular longitudinal position on the measured refraction was determined; this produced errors identical to those for vertex errors with ophthalmic lenses. CONCLUSION: For image-size principle autorefractors, simple equations describe the dependence of measured refraction on the height and angle of the instrument beam as it enters the eye and the angle of the light, reflected back from the retina, after it exits the eye. Further work will investigate the validity of such instruments for determining peripheral refraction.

The use of autorefractors using the image-size principle in determining on-axis and off-axis refraction. Part 2: Theoretical study of peripheral refraction with the Grand Seiko AutoRef/Keratometer WAM-5500.

PURPOSE: To determine, through simulations, the likely validity of Grand-Seiko autorefractors with annular targets in peripheral refraction. METHODS: Using a physical model eye, the distance inside the eye to which the Grand Seiko AutoRef/Keratometer WAM-5500 beam was converging and the effective size of its outer diameter at the cornea were determined. Grand-Seiko refraction was calculated from Rx  = (θ + α)/h1 , where θ is the angle of the ingoing radiation beam, h1 is the height of the beam at the anterior cornea and α is the angle of the beam emerging from the eye following reflection at the retina. Two eye models were used: a Navarro schematic eye and a Navarro schematic eye with a contact lens having a highly positive aspheric front surface. RESULTS: The instrument beam was determined to be converging towards the eye to a distance of 24.4 mm behind the corneal vertex, with a 2.46 mm effective size outer diameter of the beam at the anterior cornea. The Grand-Seiko refractions provided accurate estimates of peripheral refraction for the model eyes. The results were closer to Zernike refractions than to Zernike paraxial refraction. Spherical aberration influenced refraction by up to 0.5 D, and peripheral coma had limited influence. CONCLUSION: Grand-Seiko autorefractors in current use, and having a circular annulus with an ingoing effective outer diameter at the front of the eye of about 2.4 mm, are likely to give valid peripheral refractions.

High Resource Utilization in Emergent Versus Elective General Surgery.

BACKGROUND: In an era of pay for performance metrics, we sought to increase understanding of factors driving high resource utilization (HRU) in emergent (EGS) versus same-day elective (SDGS) general surgery patients. METHODS: General surgery procedures from the 2016 ACS-NSQIP public use file were grouped according to the first four digits of the primary procedure CPT code. Groups having at least 100 of both elective and emergent cases were included (22 groups; 83,872 cases). HRU patients were defined as those in-hospital >7D, returned to the OR, readmitted, and/or had morbidity likely requiring an intensive care unit (ICU)stay. Independent NSQIP predictors of HRU were identified through forward regression; P for entry < 0.05, for exit > 0.10. RESULTS: Of all patients, 33% were HRU. The three highest HRU procedures (total colectomy, enterolysis, and ileostomy) comprised a higher proportion of EGS than SDGS cases (10.3 versus 2.6%, P < 0.001). The duration of operation was 40 Min lower in EGS after adjustment. Thirty-nine of the remaining 40 HRU predictors were higher in EGS including preoperative SIRS/Sepsis (50 versus 2%), ASA classification IV-V (31 versus 5%), albumin <3.5 g/dL (40 versus 12%), transfers (26 versus 2%, P's < 0.001), septuagenarians (35 versus 25%) and disseminated cancer (6.3 versus 4.8%, P's < 0.001); while sex did not differ. After adjustment, EGS patients remained more likely to be HRU (odds ratio 2.5, 95% CI 2.4 - 2.6, P < 0.001). CONCLUSIONS: EGS patients utilize significantly more resources than SDGS patients above what can be adjusted for in the clinically robust ACS-NSQIP dataset. Distinctive payment and value-based performance models are necessary for EGS.

Silver Adsorption on Calcium Niobate(001) Nanosheets: Calorimetric Energies That Explain Sinter-Resistant Support.

Metal nanoparticles deposited on oxide supports are essential to many technologies, including catalysts, fuel cells, and electronics. Therefore, understanding the chemical bonding strength between metal nanoparticles and oxide surfaces is of great interest. The adsorption energetics, adhesion energy, and adsorbate structure of Ag on dehydrated HCa2Nb3O10(001) nanosheets at 300 K have been studied using metal adsorption calorimetry and surface spectroscopies. These dehydrated ("dh") calcium niobate nanosheets (dh-HCa2Nb3O10(001)) have the stoichiometry Ca4Nb6O19. They impart unusual stability to metal nanoparticles when used as catalyst supports and are easy-to-prepare by Langmuir-Blodgett (LB) techniques, highly ordered, and essentially single-crystal surfaces of mixed oxides with a huge ratio of terrace to edge sites. Below the monolayer coverage, Ag grows on dh-HCa2Nb3O10(001) as 2D islands of thickness ∼2 layers. The differential heat of Ag adsorption is initially ∼303 kJ/mol, increasing slowly to ∼338 kJ/mol by 0.8 ML. At higher coverages, Ag atoms mainly add on top of these 2D islands, growing 3D nanoparticles of increasing thickness, as the heat decreases asymptotically toward silver's heat of sublimation (285 kJ/mol). The adhesion energy of Ag(s) to this Ca niobate surface is estimated to be 4.33 J/m2, larger than that on any oxide surface previously measured. This explains the sinter resistance reported for metal nanoparticles on this support. Electron transfer from Ag into the calcium niobate is also measured. These results demonstrate an easy way to do single-crystal-type surface science studies-and especially thermochemical measurements-on the complex surfaces of mixed oxides: using LB-deposited perovskite nanosheets and ultrahigh-vacuum annealing in O2.

Energies of Adsorbed Catalytic Intermediates on Transition Metal Surfaces: Calorimetric Measurements and Benchmarks for Theory.

Better catalysts and electrocatalysts are essential for the production and use of clean fuels with less pollution and improved energy efficiency, for making chemicals with less energy and environmental impact, for pollution abatement, and for many other future technologies needed to achieve environmentally friendlier energy supply and chemicals industry. Crucial for rational design of better catalyst and electrocatalyst materials is knowledge of the energies of elementary chemical reactions on late transition metal surfaces. This knowledge would also aid in designing more efficient and stable photocatalysts and batteries for harvesting and storing solar energy. These are all crucial for sustainable living with high quality. Herein, I review measurements of surface reaction energies involving many of the most common adsorbates formed as intermediates on late transition metal surfaces in catalytic and electrocatalytic reactions of interest for energy and environmental technologies. I focus on calorimetric measurements of the heat of molecular and dissociative adsorption of gases on single crystals (i.e., single crystal adsorption calorimetry, or SCAC) that allow the heats of formation of adsorbed intermediates in well-defined structures to be directly determined. Adsorption reactions are often irreversible, and in such cases SCAC is required to get these heats, since the other methods for measuring adsorption energies (equilibrium adsorption isotherms and temperature-programmed desorption) work only for reversible adsorption. Common examples of irreversible adsorption reactions are ones that produce adsorbed molecular fragments or adsorbed molecules such as olefins and aromatic molecules that bind very strongly to non-noble metals. When the heats of formation of different adsorbed molecular fragments are compared to each other, and to their values on different metal surfaces, they reveal which properties of the metal surface and the molecular fragments determine metal-adsorbate bond strengths, and clarify differences in catalytic reactivity between different metals. When combined with earlier adsorption energy measurements, these heats also provide a database of reliable energies of adsorbed catalytic intermediates that serve as crucial benchmarks to guide the development of improved computational methods for calculating the energetics of elementary steps on late transition metal surfaces (i.e., reaction energies and activation barriers), such as density functional theory. The energy accuracy of such computational estimates is crucial for the future of catalysis research and catalyst discovery.

Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systemic Review and Meta-Analysis.

BACKGROUND: Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. METHODS: MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. RESULTS: Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; P < 0.001), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, P = 0.14 and OR 1.23; CI: 0.96-1.58, P = 0.101, respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, P = 0.0048 and 4.88: 95% CI 0.756 to 9.0133, P = 0.0204, respectively). CONCLUSIONS: Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients.

The physical chemistry and materials science behind sinter-resistant catalysts.

Catalyst sintering, a main cause of the loss of catalytic activity and/or selectivity at high reaction temperatures, is a major concern and grand challenge in the general area of heterogeneous catalysis. Although all heterogeneous catalysts are inevitably subjected to sintering during their operation, the immediate and drastic consequences can be mitigated by carefully engineering the catalytic particles and their interactions with the supports. In this tutorial review, we highlight recent progress in understanding the physical chemistry and materials science involved in sintering, including the discussion of advanced techniques, such as in situ microscopy and spectroscopy, for investigating the sintering process and its rate. We also discuss strategies for the design and rational fabrication of sinter-resistant catalysts. Finally, we showcase recent success in improving the thermal stability and thus sinter resistance of supported catalytic systems.

Origin of Thermal and Hyperthermal CO2 from CO Oxidation on Pt Surfaces: The Role of Post-Transition-State Dynamics, Active Sites, and Chemisorbed CO2.

The post-transition-state dynamics in CO oxidation on Pt surfaces are investigated using DFT-based ab initio molecular dynamics simulations. While the initial CO2 formed on a terrace site on Pt(111) desorbs directly, it is temporarily trapped in a chemisorption well on a Pt(332) step site. These two reaction channels thus produce CO2 with hyperthermal and thermal velocities with drastically different angular distributions, in agreement with recent experiments (Nature, 2018, 558, 280-283). The chemisorbed CO2 is formed by electron transfer from the metal to the adsorbate, resulting in a bent geometry. While chemisorbed CO2 on Pt(111) is unstable, it is stable by 0.2 eV on a Pt(332) step site. This helps explain why newly formed CO2 produced at step sites desorbs with far lower translational energies than those formed at terraces. This work shows that steps and other defects could be potentially important in finding optimal conditions for the chemical activation and dissociation of CO2 .

Energetics of van der Waals Adsorption on the Metal-Organic Framework NU-1000 with Zr6-oxo, Hydroxo, and Aqua Nodes.

We report measurements of adsorption isotherms and the determination of the isosteric heats of adsorption of several small gases (H2, D2, Ne, N2, CO, CH4, C2H6, Ar, Kr, and Xe) on the metal-organic framework (MOF) NU-1000, which is one of the most thermally stable MOFs. It has transition-metal nodes of formula Zr6(µ3-OH)4(µ3-O)4(OH)4(OH2)4 that resemble hydrated ZrO2 clusters and can serve as catalysts or catalyst supports. The linkers in this MOF are pyrenes linked to the nodes via the carboxylate groups of benzoates. The broad range of adsorbates studied here allows us to compare trends both with adsorption on other surfaces and with density functional calculations also presented here. The experimental isotherms indicate similar filling of the MOF surface by the different gases, starting with strong adsorption sites near the Zr atoms, a result corroborated by the density functional calculations. This adsorption is followed by the filling of other adsorption sites on the nodes and organic framework. Capillary condensation occurs in wide pores after completion of a monolayer. The total amount adsorbed for all the gases is the equivalent of two complete monolayers. The experimental isosteric heats of adsorption are nearly proportional to the atom-atom (or molecule-molecule) Lennard-Jones well-depth parameters of the adsorbates but ∼13-fold larger. The density functional calculations show a similar trend but with much more scatter and heats that are usually greater (by 30%, on average).

Sortilin regulates sorting and secretion of Sonic hedgehog.

Sonic Hedgehog (Shh) is a secreted morphogen that is an essential regulator of patterning and growth. The Shh full-length protein undergoes autocleavage in the endoplasmic reticulum to generate the biologically active N-terminal fragment (ShhN), which is destined for secretion. We identified sortilin (Sort1), a member of the VPS10P-domain receptor family, as a new Shh trafficking receptor. We demonstrate that Sort-Shh interact by performing coimmunoprecipitation and proximity ligation assays in transfected cells and that they colocalize at the Golgi. Sort1 overexpression causes re-distribution of ShhN and, to a lesser extent, of full-length Shh to the Golgi and reduces Shh secretion. We show loss of Sort1 can partially rescue Hedgehog-associated patterning defects in a mouse model that is deficient in Shh processing, and we show that Sort1 levels negatively regulate anterograde Shh transport in axons in vitro and Hedgehog-dependent axon-glial interactions in vivo Taken together, we conclude that Shh and Sort1 can interact at the level of the Golgi and that Sort1 directs Shh away from the pathways that promote its secretion.

Bond Energies of Adsorbed Intermediates to Metal Surfaces: Correlation with Hydrogen-Ligand and Hydrogen-Surface Bond Energies and Electronegativities.

Understanding what controls the strength of bonding of adsorbed intermediates to transition-metal surfaces is of central importance in many technologies, especially catalysis and electrocatalysis. Our recently measured bond enthalpies of -OH, -OCH3 , -O(O)CH and -CH3 to Pt(111) and Ni(111) surfaces are fit well (standard deviation of 7.2 kJ mol-1 ) by a predictive equation involving only known parameters (gas-phase ligand-hydrogen bond enthalpies, bond enthalpies of adsorbed H atoms to that surface, electronegativities of the elements, and group electronegativities of the ligands). This equation is based upon Pauling's equation, with improvements introduced by Matcha, derived here following manipulations of Matcha's equation similar to (but going beyond) those introduced by Schock and Marks to explain ligand-metal bond enthalpy trends in organometallic complexes.

A Notch-Gli2 axis sustains Hedgehog responsiveness of neural progenitors and Müller glia.

Neurogenesis is regulated by the dynamic and coordinated activity of several extracellular signalling pathways, but the basis for crosstalk between these pathways remains poorly understood. Here we investigated regulatory interactions between two pathways that are each required for neural progenitor cell maintenance in the postnatal retina; Hedgehog (Hh) and Notch signalling. Both pathways are activated in progenitor cells in the postnatal retina based on the co-expression of fluorescent pathway reporter transgenes at the single cell level. Disrupting Notch signalling, genetically or pharmacologically, induces a rapid downregulation of all three Gli proteins and inhibits Hh-induced proliferation. Ectopic Notch activation, while not sufficient to promote Hh signalling or proliferation, increases Gli2 protein. We show that Notch regulation of Gli2 in Müller glia renders these cells competent to proliferate in response to Hh. These data suggest that Notch signalling converges on Gli2 to prime postnatal retinal progenitor cells and Müller glia to proliferate in response to Hh.

Using degrees of rate control to improve selective n-butane oxidation over model MOF-encapsulated catalysts: sterically-constrained Ag3Pd(111).

Metal nanoparticles encapsulated within metal organic frameworks (MOFs) offer steric restrictions near the catalytic metal that can improve selectivity, much like in enzymes. A microkinetic model is developed for the regio-selective oxidation of n-butane to 1-butanol with O2 over a model for MOF-encapsulated bimetallic nanoparticles. The model consists of a Ag3Pd(111) surface decorated with a 2-atom-thick ring of (immobile) helium atoms which creates an artificial pore of similar size to that in common MOFs, which sterically constrains the adsorbed reaction intermediates. The kinetic parameters are based on energies calculated using density functional theory (DFT). The microkinetic model was analysed at 423 K to determine the dominant pathways and which species (adsorbed intermediates and transition states in the reaction mechanism) have energies that most sensitively affect the reaction rates to the different products, using degree-of-rate-control (DRC) analysis. This analysis revealed that activation of the C-H bond is assisted by adsorbed oxygen atoms, O*. Unfortunately, O* also abstracts H from adsorbed 1-butanol and butoxy as well, leading to butanal as the only significant product. This suggested to (1) add water to produce more OH*, thus inhibiting these undesired steps which produce OH*, and (2) eliminate most of the O2 pressure to reduce the O* coverage, thus also inhibiting these steps. Combined with increasing butane pressure, this dramatically improved the 1-butanol selectivity (from 0 to 95%) and the rate (to 2 molecules per site per s). Moreover, 40% less O2 was consumed per oxygen atom in the products. Under these conditions, a terminal H in butane is directly eliminated to the Pd site, and the resulting adsorbed butyl combines with OH* to give the desired 1-butanol. These results demonstrate that DRC analysis provides a powerful approach for optimizing catalytic process conditions, and that highly selectivity oxidation can sometimes be achieved by using a mixture of O2 and H2O as the oxidant. This was further demonstrated by DRC analysis of a second microkinetic model based on a related but hypothetical catalyst, where the activation energies for two of the steps were modified.

Cardiac ScoreCard: A Diagnostic Multivariate Index Assay System for Predicting a Spectrum of Cardiovascular Disease.

Clinical decision support systems (CDSSs) have the potential to save lives and reduce unnecessary costs through early detection and frequent monitoring of both traditional risk factors and novel biomarkers for cardiovascular disease (CVD). However, the widespread adoption of CDSSs for the identification of heart diseases has been limited, likely due to the poor interpretability of clinically relevant results and the lack of seamless integration between measurements and disease predictions. In this paper we present the Cardiac ScoreCard-a multivariate index assay system with the potential to assist in the diagnosis and prognosis of a spectrum of CVD. The Cardiac ScoreCard system is based on lasso logistic regression techniques which utilize both patient demographics and novel biomarker data for the prediction of heart failure (HF) and cardiac wellness. Lasso logistic regression models were trained on a merged clinical dataset comprising 579 patients with 6 traditional risk factors and 14 biomarker measurements. The prediction performance of the Cardiac ScoreCard was assessed with 5-fold cross-validation and compared with reference methods. The experimental results reveal that the ScoreCard models improved performance in discriminating disease versus non-case (AUC = 0.8403 and 0.9412 for cardiac wellness and HF, respectively), and the models exhibit good calibration. Clinical insights to the prediction of HF and cardiac wellness are provided in the form of logistic regression coefficients which suggest that augmenting the traditional risk factors with a multimarker panel spanning a diverse cardiovascular pathophysiology provides improved performance over reference methods. Additionally, a framework is provided for seamless integration with biomarker measurements from point-of-care medical microdevices, and a lasso-based feature selection process is described for the down-selection of biomarkers in multimarker panels.

The effect of rosuvastatin on thromboinflammation in the setting of acute coronary syndrome.

In patients with acute coronary syndromes (ACS), early therapy with high-dose statins may reduce short-term adverse clinical outcomes. The mechanisms responsible are not known but could involve anti-inflammatory or anti-thrombotic effects. Compelling evidence from experimental models and clinical studies suggests that the interplay between inflammatory and thrombotic systems, typified by platelet-monocyte and platelet-neutrophil interactions, might be a key regulator of ischemic vascular events. The study sought to determine if early, high-dose administration of the HMG-CoA reductase inhibitor rosuvastatin in the setting of ACS exerts beneficial vascular effects by reducing, and inhibiting biomarkers of thromboinflammation, such as platelet-monocyte and platelet-neutrophil interactions, and biomarkers of myocardial necrosis. A total of 54 patients presenting with ACS within 8 h of symptom onset were randomized to rosuvastatin 40 mg or placebo. Rosuvastatin significantly reduced interactions between platelets and circulating neutrophils (P = 0.015) and monocytes (P = 0.009) within 24 h. No significant effects were observed on platelet aggregation or plasma levels of PF4, sP-selectin, or sCD40L, whereas significant reductions of RANTES occurred over time in both treatment groups. Plasma levels of myeloperoxidase (MPO) declined more rapidly with rosuvastatin therapy than placebo. In a subset of patients with normal cardiac necrosis biomarkers at randomization, rosuvastatin therapy was associated with less myocardial damage as measured by troponin-I or CK-MB. Early administration of high-dose statin therapy in patients with ACS appears to improve biomarkers of inflammation within 8 h, which may translate into fewer ischemic events.