Intravenous lipid emulsion in clinical toxicology

Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose

Epinephrine Impairs Lipid Resuscitation from Bupivacaine Overdose

Background Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose. Methods Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml x kg x min, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min. Results Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min. Conclusions Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia

Thermodynamics and dark energy

A significant observational effort has been directed to unveil the nature of the so-called dark energy. However, given the large number of theoretical possibilities, it is possible that such a task cannot be performed on the basis only of the observational data. In this article we discuss some thermodynamic properties of this energy component by assuming that its constituents are massless quanta with a general time-dependent equation-of-state parameter $\omega(z)=\omega_0 + \omega_a f(z)$, where $\omega_0$ and $\omega_a$ are constants and $f(z)$ may assume different forms. We show that very restrictive bounds can be placed on the $w_0$ - $w_a$ space when current observational data are combined with the thermodynamic constraints derived.Comment: 5 pages, 3 figures, LaTe

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. Methods After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. Results All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. Conclusions Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade

Loop-Generated Bounds on Changes to the Graviton Dispersion Relation

We identify the effective theory appropriate to the propagation of massless bulk fields in brane-world scenarios, to show that the dominant low-energy effect of asymmetric warping in the bulk is to modify the dispersion relation of the effective 4-dimensional modes. We show how such changes to the graviton dispersion relation may be bounded through the effects they imply, through loops, for the propagation of standard model particles. We compute these bounds and show that they provide, in some cases, the strongest constraints on nonstandard gravitational dispersions. The bounds obtained in this way are the strongest for the fewest extra dimensions and when the extra-dimensional Planck mass is the smallest. Although the best bounds come for warped 5-D scenarios, for which the 5D Planck Mass is O(TeV), even in 4 dimensions the graviton loop can lead to a bound on the graviton speed which is comparable with other constraints.Comment: 18 pages, LaTeX, 4 figures, uses revte

Testing for Home Team and Favorite Biases in the Australian Rules Football Fixed-Odds and Point Spread Betting Markets

In this paper, we test two different kinds of bias; the favorite-longshot/favorite-underdog and the home team bias, and distinguish between the two, using a distinctive feature of the Australian Football League (AFL), that many games are played on neutral grounds. This is the first empirical study, to the best of our knowledge, to make a clear distinction between the two types of bias. We conduct our tests by subjecting 2001-2004 data for the AFL to detailed scrutiny, using standard econometric weak-form efficiency models of point spread and fixed odds betting markets. Where the results suggest the presence of a bias, we test potential profitability via betting simulation. We are able to reject the existence of any significant pure favorite-longshot/favorite-underdog bias in either market, and to demonstrate the existence of a significant bias in favor of teams with an apparent home ground advantage in games played outside Victoria in the point spread market and in the fixed odds market during 2002, 2004 and the period as a whole. Games in Melbourne and in Geelong are free of such a bias (except for 2003 in the point spread market in Geelong). Betting simulations which attempt to exploit these inefficiencies yield modest profits

The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1

DMF (dimethyl fumarate) exerts anti-inflammatory and pro-metabolic effects in a variety of cell types, and a formulation (BG-12) is being evaluated for monotherapy in multiple sclerosis patients. DMF modifies glutathione (GSH) levels that can induce expression of the anti-inflammatory protein HO-1 (haem oxygenase-1). In primary astrocytes and C6 glioma cells, BG-12 dose-dependently suppressed nitrite production induced by either LI [LPS (lipopolysaccharide) at 1 \u3bcg/ml plus IFN\u3b3 (interferon \u3b3) at 20 units/ml] or a mixture of pro-inflammatory cytokines, with greater efficacy in C6 cells. BG-12 reduced NOS2 (nitric oxide synthase 2) mRNA levels and activation of a NOS2 promoter, reduced nuclear levels of NF-\u3baB (nuclear factor \u3baB) p65 subunit and attenuated loss of I\u3baB\u3b1 (inhibitory \u3baB\u3b1) in both cell types, although with greater effects in astrocytes. In astrocytes, LI decreased mRNA levels for GSHr (GSH reductase) and GCL (c-glutamylcysteine synthetase), and slightly suppressed GSHs (GSH synthetase) mRNAs. Co-treatment with BG-12 prevented those decreased and increased levels above control values. In contrast, LI reduced GSHp (GSH peroxidase) and GCL in C6 cells, and BG-12 had no effect on those levels. BG-12 increased nuclear levels of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), an inducer of GSH-related enzymes, in astrocytes but not C6 cells. In astrocytes, GSH was decreased by BG-12 at 2 h and increased at 24 h. Prior depletion of GSH using buthionine-sulfoximine increased the ability of BG-12 to reduce nitrites. In astrocytes, BG-12 increased HO-1 mRNA levels and effects on nitrite levels were blocked by an HO-1 inhibitor. These results demonstrate that BG-12 suppresses inflammatory activation in astrocytes and C6 glioma cells, but with distinct mechanisms, different dependence on GSH and different effects on transcription factor activation

d=3 Bosonic Vector Models Coupled to Chern-Simons Gauge Theories

We study three dimensional O(N)_k and U(N)_k Chern-Simons theories coupled to a scalar field in the fundamental representation, in the large N limit. For infinite k this is just the singlet sector of the O(N) (U(N)) vector model, which is conjectured to be dual to Vasiliev's higher spin gravity theory on AdS_4. For large k and N we obtain a parity-breaking deformation of this theory, controlled by the 't Hooft coupling lambda = 4 \pi N / k. For infinite N we argue (and show explicitly at two-loop order) that the theories with finite lambda are conformally invariant, and also have an exactly marginal (\phi^2)^3 deformation. For large but finite N and small 't Hooft coupling lambda, we show that there is still a line of fixed points parameterized by the 't Hooft coupling lambda. We show that, at infinite N, the interacting non-parity-invariant theory with finite lambda has the same spectrum of primary operators as the free theory, consisting of an infinite tower of conserved higher-spin currents and a scalar operator with scaling dimension \Delta=1; however, the correlation functions of these operators do depend on lambda. Our results suggest that there should exist a family of higher spin gravity theories, parameterized by lambda, and continuously connected to Vasiliev's theory. For finite N the higher spin currents are not conserved.Comment: 34 pages, 29 figures. v2: added reference

Model-Independent Reconstruction of the Expansion History of the Universe from Type Ia Supernovae

Based on the largest homogeneously reduced set of Type Ia supernova luminosity data currently available -- the Union2 sample -- we reconstruct the expansion history of the Universe in a model-independent approach. Our method tests the geometry of the Universe directly without reverting to any assumptions made on its energy content. This allows us to constrain Dark Energy models and non-standard cosmologies in a straightforward way. The applicability of the presented method is not restricted to testing cosmological models. It can be a valuable tool for pointing out systematic errors hidden in the supernova data and planning future Type Ia supernova cosmology campaigns.Comment: 10 pages, 8 figures, to be published in Montly Notices of the Royal Astronomical Societ

Galactic halo cusp-core: tidal compression in mergers

We explain in simple terms how the buildup of dark haloes by merging compact satellites, as in the CDM cosmology, inevitably leads to an inner cusp of density profile $\rho \propto r^{-\alpha}$ with \alpha \gsim 1, as seen in cosmological N-body simulations. A flatter halo core with $\alpha <1$ exerts on the satellites tidal compression in all directions, which prevents deposit of stripped satellite material in the core region. This makes the satellite orbits decay from the radius where $\alpha \sim 1$ to the halo centre with no local tidal mass transfer and thus causes a rapid steepening of the inner profile to $\alpha >1$. These tidal effects, the resultant steepening of the profile to a cusp, and the stability of this cusp to tandem mergers with compact satellites, are demonstrated using N-body simulations. The transition at $\alpha \sim 1$ is then addressed using toy models in the limiting cases of impulse and adiabatic approximations and using tidal radii for satellites on radial and circular orbits. In an associated paper we address the subsequent slow convergence from either side to an asymptotic stable cusp with \alpha \gsim 1. Our analysis thus implies that an inner cusp is enforced when small haloes are typically more compact than larger haloes, as in the CDM scenario, such that enough satellite material makes it intact into the inner halo and is deposited there. We conclude that a necessary condition for maintaining a flat core, as indicated by observations, is that the inner regions of the CDM satellite haloes be puffed up by about 50% such that when they merge into a bigger halo they would be disrupted outside the halo core. This puffing up could be due to baryonic feedback processes in small haloes, which may be stimulated by the tidal compression in the halo cores.Comment: 19 pages, Latex, mn2e.cls, some revisions, MNRAS in pres