Diversification and hybridization in firm knowledge bases in nanotechnologies

The paper investigates the linkages between the characteristics of technologies and the structure of a firms' knowledge base. Nanotechnologies have been defined as converging technologies that operate at the nanoscale, and which require integration to fulfill their economic promises. Based on a worldwide database of nanofirms, the paper analyses the degree of convergence and the convergence mechanisms within firms. It argues that the degree of convergence in a firm's nano-knowledge base is relatively independent from the size of the firm's nano-knowledge base. However, while firms with small nano-knowledge bases tend to exploit convergence in each of their patents/publications, firms with large nano-knowledge bases tend to separate their nano-R&D activities in the different established fields and achieve diversity through the juxtaposition of the output of these independent activitie

Reconciling observed and simulated stellar halo masses

We use cosmological hydrodynamical simulations of Milky-Way-mass galaxies from the FIRE project to evaluate various strategies for estimating the mass of a galaxy's stellar halo from deep, integrated-light images. We find good agreement with integrated-light observations if we mimic observational methods to measure the mass of the stellar halo by selecting regions of an image via projected radius relative to the disk scale length or by their surface density in stellar mass . However, these observational methods systematically underestimate the accreted stellar component, defined in our (and most) simulations as the mass of stars formed outside of the host galaxy, by up to a factor of ten, since the accreted component is centrally concentrated and therefore substantially obscured by the galactic disk. Furthermore, these observational methods introduce spurious dependencies of the estimated accreted stellar component on the stellar mass and size of galaxies that can obscure the trends in accreted stellar mass predicted by cosmological simulations, since we find that in our simulations the size and shape of the central galaxy is not strongly correlated with the assembly history of the accreted stellar halo. This effect persists whether galaxies are viewed edge-on or face-on. We show that metallicity or color information may provide a way to more cleanly delineate in observations the regions dominated by accreted stars. Absent additional data, we caution that estimates of the mass of the accreted stellar component from single-band images alone should be taken as lower limits.Comment: Version accepted by Ap

Simulating galaxies in the reionization era with FIRE-2: morphologies and sizes

We study the morphologies and sizes of galaxies at z>5 using high-resolution cosmological zoom-in simulations from the Feedback In Realistic Environments project. The galaxies show a variety of morphologies, from compact to clumpy to irregular. The simulated galaxies have more extended morphologies and larger sizes when measured using rest-frame optical B-band light than rest-frame UV light; sizes measured from stellar mass surface density are even larger. The UV morphologies are usually dominated by several small, bright young stellar clumps that are not always associated with significant stellar mass. The B-band light traces stellar mass better than the UV, but it can also be biased by the bright clumps. At all redshifts, galaxy size correlates with stellar mass/luminosity with large scatter. The half-light radii range from 0.01 to 0.2 arcsec (0.05-1 kpc physical) at fixed magnitude. At z>5, the size of galaxies at fixed stellar mass/luminosity evolves as (1+z)^{-m}, with m~1-2. For galaxies less massive than M_star~10^8 M_sun, the ratio of the half-mass radius to the halo virial radius is ~10% and does not evolve significantly at z=5-10; this ratio is typically 1-5% for more massive galaxies. A galaxy's "observed" size decreases dramatically at shallower surface brightness limits. This effect may account for the extremely small sizes of z>5 galaxies measured in the Hubble Frontier Fields. We provide predictions for the cumulative light distribution as a function of surface brightness for typical galaxies at z=6.Comment: 11 pages, 11 figures, resubmitted to MNRAS after revision for referee's comment

Formation of Globular Cluster Candidates in Merging Proto-galaxies at High Redshift: A View from the FIRE Cosmological Simulations

Using a state-of-the-art cosmological simulation of merging proto-galaxies at high redshift from the FIRE project, with explicit treatments of star formation and stellar feedback in the interstellar medium, we investigate the formation of star clusters and examine one of the formation hypothesis of present-day metal-poor globular clusters. We find that frequent mergers in high-redshift proto-galaxies could provide a fertile environment to produce long-lasting bound star clusters. The violent merger event disturbs the gravitational potential and pushes a large gas mass of ~> 1e5-6 Msun collectively to high density, at which point it rapidly turns into stars before stellar feedback can stop star formation. The high dynamic range of the reported simulation is critical in realizing such dense star-forming clouds with a small dynamical timescale, t_ff <~ 3 Myr, shorter than most stellar feedback timescales. Our simulation then allows us to trace how clusters could become virialized and tightly-bound to survive for up to ~420 Myr till the end of the simulation. Because the cluster's tightly-bound core was formed in one short burst, and the nearby older stars originally grouped with the cluster tend to be preferentially removed, at the end of the simulation the cluster has a small age spread.Comment: 14 pages, 14 figures, Accepted for publication in the Monthly Notices of the Royal Astronomical Society, High-resolution version of this article also available at http://www.jihoonkim.org/index/research.html#g

The methodological and reporting quality of systematic reviews from China and the USA are similar

Objective: To compare the methodological and reporting quality of systematic reviews by authors from China and those from the United States (the USA). Study Design: From systematic reviews of randomised trials published in 2014 in English, we randomly selected 100 from China and 100 from the USA. The methodological quality was assessed using the AMSTAR tool, and reporting quality assessed using the PRISMA tool. Results: Compared with systematic reviews from the USA, those from China were more likely to be a meta-analysis, published in low impact journals, and a non-Cochrane review. The mean summary AMSTAR score was 6.7 (95% confidence interval: 6.5 to 7.0) for reviews from China and 6.6 (6.1 to 7.1) for reviews from the USA, and the mean summary PRISMA score was 21.2 (20.7 to 21.6) for reviews from China and 20.6 (19.9 to 21.3) for reviews from the USA. The differences in summary quality scores between China and the USA were statistically non-significant after adjusting for multiple review factors. Conclusions: The overall methodological and reporting quality of systematic reviews by authors from China are similar to those from the USA, although the quality of systematic reviews from both countries could be further improved

PAR4 (Protease-Activated Receptor 4) Antagonism with BMS-986120 Inhibits Human Ex Vivo Thrombus Formation

Objective-BMS-986120 is a novel first-in-class oral PAR4 (protease-Activated receptor 4) antagonist with potent and selective antiplatelet effects. We sought to determine for the first time, the effect of BMS-986120 on human ex vivo thrombus formation. Approach and Results-Forty healthy volunteers completed a phase 1 parallel-group PROBE trial (Prospective Randomized Open-Label Blinded End Point). Ex vivo platelet activation, platelet aggregation, and thrombus formation were measured at 0, 2, and 24 hours after (1) oral BMS-986120 (60 mg) or (2) oral aspirin (600 mg) followed at 18 hours with oral aspirin (600 mg) and oral clopidogrel (600 mg). BMS-986120 demonstrated highly selective and reversible inhibition of PAR4 agonist peptide (100 μM)-stimulated P-selectin expression, platelet-monocyte aggregates, and platelet aggregation (P<0.001 for all). Compared with pretreatment, total thrombus area (μm2/mm) at high shear was reduced by 29.2% (95% confidence interval, 18.3%-38.7%; P<0.001) at 2 hours and by 21.4% (9.3%-32.0%; P=0.002) at 24 hours. Reductions in thrombus formation were driven by a decrease in platelet-rich thrombus deposition: 34.8% (19.3%-47.3%; P<0.001) at 2 hours and 23.3% (5.1%-38.0%; P=0.016) at 24 hours. In contrast to aspirin alone, or in combination with clopidogrel, BMS-986120 had no effect on thrombus formation at low shear (P=nonsignificant). BMS-986120 administration was not associated with an increase in coagulation times or serious adverse events. Conclusions-BMS-986120 is a highly selective and reversible oral PAR4 antagonist that substantially reduces platelet-rich thrombus formation under conditions of high shear stress. Our results suggest PAR4 antagonism has major potential as a therapeutic antiplatelet strategy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439190

FIRE-2 Simulations: Physics versus Numerics in Galaxy Formation

The Feedback In Realistic Environments (FIRE) project explores feedback in cosmological galaxy formation simulations. Previous FIRE simulations used an identical source code (“FIRE-1”) for consistency. Motivated by the development of more accurate numerics – including hydrodynamic solvers, gravitational softening, and supernova coupling algorithms – and exploration of new physics (e.g. magnetic fields), we introduce “FIRE-2”, an updated numerical implementation of FIRE physics for the GIZMO code. We run a suite of simulations and compare against FIRE-1: overall, FIRE-2 improvements do not qualitatively change galaxy-scale properties. We pursue an extensive study of numerics versus physics. Details of the star-formation algorithm, cooling physics, and chemistry have weak effects, provided that we include metal-line cooling and star formation occurs at higher-than-mean densities. We present new resolution criteria for high-resolution galaxy simulations. Most galaxy-scale properties are robust to numerics we test, provided: (1) Toomre masses are resolved; (2) feedback coupling ensures conservation, and (3) individual supernovae are time-resolved. Stellar masses and profiles are most robust to resolution, followed by metal abundances and morphologies, followed by properties of winds and circum-galactic media (CGM). Central (∼kpc) mass concentrations in massive (>L*) galaxies are sensitive to numerics (via trapping/recycling of winds in hot halos). Multiple feedback mechanisms play key roles: supernovae regulate stellar masses/winds; stellar mass-loss fuels late star formation; radiative feedback suppresses accretion onto dwarfs and instantaneous star formation in disks. We provide all initial conditions and numerical algorithms used

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching