Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): : a randomised, double-blind, placebo-controlled trial

This document is the Accepted Manuscript version of the following article: Valerie J. Page, et al, ‘Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial’, The Lancet Respiratory Medicine, Vol. 5 (9): 727-737, September 2017. Under embargo until 19 July 2018. The final, definitive version is available online at doi: https://doi.org/10.1016/S2213-2600(17)30234-5.Summary Background Delirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma. Methods We undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989. Findings Between Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI −1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug. Interpretation These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients. Funding National Institute for Health Research.Peer reviewedFinal Accepted Versio

Evidence for a narrow dip structure at 1.9 GeV/c2^2 in 3π+3π−3\pi^+ 3\pi^- diffractive photoproduction

A narrow dip structure has been observed at 1.9 GeV/c$^2$ in a study of diffractive photoproduction of the $~3\pi^+3\pi^-$ final state performed by the Fermilab experiment E687.Comment: The data of Figure 6 can be obtained by downloading the raw data file e687_6pi.txt. v5 (2nov2018): added Fig. 7, the 6 pion energy distribution as requested by a reade

From the Big Bang Theory to the Theory of a Stationary Universe

We consider chaotic inflation in the theories with the effective potentials phi^n and e^{\alpha\phi}. In such theories inflationary domains containing sufficiently large and homogeneous scalar field \phi permanently produce new inflationary domains of a similar type. We show that under certain conditions this process of the self-reproduction of the Universe can be described by a stationary distribution of probability, which means that the fraction of the physical volume of the Universe in a state with given properties (with given values of fields, with a given density of matter, etc.) does not depend on time, both at the stage of inflation and after it. This represents a strong deviation of inflationary cosmology from the standard Big Bang paradigm. We compare our approach with other approaches to quantum cosmology, and illustrate some of the general conclusions mentioned above with the results of a computer simulation of stochastic processes in the inflationary Universe.Comment: No changes to the file, but original figures are included. They substantially help to understand this paper, as well as eternal inflation in general, and what is now called the "multiverse" and the "string theory landscape." High quality figures can be found at http://www.stanford.edu/~alinde/LLMbigfigs

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure

High pTp_{T} non-photonic electron production in pp+pp collisions at s\sqrt{s} = 200 GeV

We present the measurement of non-photonic electron production at high transverse momentum ($p_T >$ 2.5 GeV/$c$) in $p$ + $p$ collisions at $\sqrt{s}$ = 200 GeV using data recorded during 2005 and 2008 by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The measured cross-sections from the two runs are consistent with each other despite a large difference in photonic background levels due to different detector configurations. We compare the measured non-photonic electron cross-sections with previously published RHIC data and pQCD calculations. Using the relative contributions of B and D mesons to non-photonic electrons, we determine the integrated cross sections of electrons ($\frac{e^++e^-}{2}$) at 3 GeV/$c < p_T <~$10 GeV/$c$ from bottom and charm meson decays to be ${d\sigma_{(B\to e)+(B\to D \to e)} \over dy_e}|_{y_e=0}$ = 4.0$\pm0.5$({\rm stat.})$\pm1.1$({\rm syst.}) nb and ${d\sigma_{D\to e} \over dy_e}|_{y_e=0}$ = 6.2$\pm0.7$({\rm stat.})$\pm1.5$({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.

Measurement of the Bottom contribution to non-photonic electron production in p+pp+p collisions at s\sqrt{s} =200 GeV

The contribution of $B$ meson decays to non-photonic electrons, which are mainly produced by the semi-leptonic decays of heavy flavor mesons, in $p+p$ collisions at $\sqrt{s} =$ 200 GeV has been measured using azimuthal correlations between non-photonic electrons and hadrons. The extracted $B$ decay contribution is approximately 50% at a transverse momentum of $p_{T} \geq 5$ GeV/$c$. These measurements constrain the nuclear modification factor for electrons from $B$ and $D$ meson decays. The result indicates that $B$ meson production in heavy ion collisions is also suppressed at high $p_{T}$.Comment: 6 pages, 4 figures, accepted by PR

Energy loss due to defect formation from 206Pb recoils in SuperCDMS germanium detectors

The Super Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory studied energy loss associated with defect formation in germanium crystals at mK temperatures using in situ 210Pb sources. We examine the spectrum of 206Pb nuclear recoils near its expected 103 keV endpoint energy and determine an energy loss of (6:08 ± 0:18)%, which we attribute to defect formation. From this result and using TRIM simulations, we extract the first experimentally determined average displacement threshold energy of 19.7+0.6−0.5 eV for germanium. This has implications for the analysis thresholds of future germanium-based dark matter searches

J/ψ polarization in p+p collisions at s=200 GeV in STAR

AbstractWe report on a polarization measurement of inclusive J/ψ mesons in the di-electron decay channel at mid-rapidity at 2<pT<6 GeV/c in p+p collisions at s=200 GeV. Data were taken with the STAR detector at RHIC. The J/ψ polarization measurement should help to distinguish between different models of the J/ψ production mechanism since they predict different pT dependences of the J/ψ polarization. In this analysis, J/ψ polarization is studied in the helicity frame. The polarization parameter λθ measured at RHIC becomes smaller towards high pT, indicating more longitudinal J/ψ polarization as pT increases. The result is compared with predictions of presently available models

J/ψ Production At Low Pt In Au+au And Cu+cu Collisions At Snn =200 Gev With The Star Detector

The J/ψ pT spectrum and nuclear modification factor (RAA) are reported for pT<5GeV/c and |y|<1 from 0% to 60% central Au+Au and Cu+Cu collisions at sNN=200GeV at STAR. A significant suppression of pT-integrated J/ψ production is observed in central Au+Au events. The Cu+Cu data are consistent with no suppression, although the precision is limited by the available statistics. RAA in Au+Au collisions exhibits a strong suppression at low transverse momentum and gradually increases with pT. The data are compared to high-pT STAR results and previously published BNL Relativistic Heavy Ion Collider results. 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