Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Euler-Heisenberg lagrangians and asymptotic analysis in 1+1 QED, part 1: Two-loop

We continue an effort to obtain information on the QED perturbation series at high loop orders, and particularly on the issue of large cancellations inside gauge invariant classes of graphs, using the example of the l - loop N - photon amplitudes in the limit of large photons numbers and low photon energies. As was previously shown, high-order information on these amplitudes can be obtained from a nonperturbative formula, due to Affleck et al., for the imaginary part of the QED effective lagrangian in a constant field. The procedure uses Borel analysis and leads, under some plausible assumptions, to a number of nontrivial predictions already at the three-loop level. Their direct verification would require a calculation of this `Euler-Heisenberg lagrangian' at three-loops, which seems presently out of reach. Motivated by previous work by Dunne and Krasnansky on Euler-Heisenberg lagrangians in various dimensions, in the present work we initiate a new line of attack on this problem by deriving and proving the analogous predictions in the simpler setting of 1+1 dimensional QED. In the first part of this series, we obtain a generalization of the formula of Affleck et al. to this case, and show that, for both Scalar and Spinor QED, it correctly predicts the leading asymptotic behaviour of the weak field expansion coefficients of the two loop Euler-Heisenberg lagrangians.Comment: 28 pages, 1 figures, final published version (minor modifications, refs. added

Predictive feedback control and Fitts' law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma - a prospective open clinical trial

Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT0067720

Shock waves in strongly coupled plasmas

Shock waves are supersonic disturbances propagating in a fluid and giving rise to dissipation and drag. Weak shocks, i.e., those of small amplitude, can be well described within the hydrodynamic approximation. On the other hand, strong shocks are discontinuous within hydrodynamics and therefore probe the microscopics of the theory. In this paper we consider the case of the strongly coupled N=4 plasma whose microscopic description, applicable for scales smaller than the inverse temperature, is given in terms of gravity in an asymptotically $AdS_5$ space. In the gravity approximation, weak and strong shocks should be described by smooth metrics with no discontinuities. For weak shocks we find the dual metric in a derivative expansion and for strong shocks we use linearized gravity to find the exponential tail that determines the width of the shock. In particular we find that, when the velocity of the fluid relative to the shock approaches the speed of light $v\to 1$ the penetration depth $\ell$ scales as $\ell\sim (1-v^2)^{1/4}$. We compare the results with second order hydrodynamics and the Israel-Stewart approximation. Although they all agree in the hydrodynamic regime of weak shocks, we show that there is not even qualitative agreement for strong shocks. For the gravity side, the existence of shock waves implies that there are disturbances of constant shape propagating on the horizon of the dual black holes.Comment: 47 pages, 8 figures; v2:typos corrected, references adde

Compatibility of neutrino DIS data and global analyses of parton distribution functions

Neutrino\antineutrino deep inelastic scattering (DIS) data provide useful constrains for the flavor decomposition in global fits of parton distribution functions (PDF). The smallness of the cross-sections requires the use of nuclear targets in the experimental setup. Understanding the nuclear corrections is, for this reason, of utmost importance for a precise determination of the PDFs. Here, we explore the nuclear effects in the neutrino\antineutrino-nucleon DIS by comparing the NuTeV, CDHSW, and CHORUS cross-sections to the predictions derived from the latest parton distribution functions and their nuclear modifications. We obtain a good description of these data and find no apparent disagreement between the nuclear effects in neutrino DIS and those in charged lepton DIS. These results also indicate that further improvements in the knowledge of the nuclear PDFs could be obtained by a more extensive use of these sets of neutrino data.Comment: 16 pages, 8 figure

Constraints for the nuclear parton distributions from Z and W production at the LHC

The LHC is foreseen to finally bring also the nuclear collisions to the TeV scale thereby providing new possibilities for physics studies, in particular related to the electro-weak sector of the Standard Model. We study here the Z and W production in proton-lead and lead-lead collisions at the LHC, concentrating on the prospects of testing the factorization and constraining the nuclear modifications of the parton distribution functions (PDFs). Especially, we find that the rapidity asymmetries in proton-nucleus collisions, arising from the differences in the PDFs between the colliding objects, provide a decisive advantage in comparison to the rapidity-symmetric nucleus-nucleus case. We comment on how such studies will help to improve our knowledge of the nuclear PDFs.Comment: The version accepted for publication in JHEP. New figures has been added, and we also discuss the single charged lepton productio

Limit on the mass of a long-lived or stable gluino

We reinterpret the generic CDF charged massive particle limit to obtain a limit on the mass of a stable or long-lived gluino. Various sources of uncertainty are examined. The $R$-hadron spectrum and scattering cross sections are modeled based on known low-energy hadron physics and the resultant uncertainties are quantified and found to be small compared to uncertainties from the scale dependence of the NLO pQCD production cross sections. The largest uncertainty in the limit comes from the unknown squark mass: when the squark -- gluino mass splitting is small, we obtain a gluino mass limit of 407 GeV, while in the limit of heavy squarks the gluino mass limit is 397 GeV. For arbitrary (degenerate) squark masses, we obtain a lower limit of 322 GeV on the gluino mass. These limits apply for any gluino lifetime longer than $\sim 30$ ns, and are the most stringent limits for such a long-lived or stable gluino.Comment: 15 pages, 5 figures, accepted for publication in JHE

The nature of localization in graphene under quantum Hall conditions

Particle localization is an essential ingredient in quantum Hall physics [1,2]. In conventional high mobility two-dimensional electron systems Coulomb interactions were shown to compete with disorder and to play a central role in particle localization [3]. Here we address the nature of localization in graphene where the carrier mobility, quantifying the disorder, is two to four orders of magnitude smaller [4,5,6,7,8,9,10]. We image the electronic density of states and the localized state spectrum of a graphene flake in the quantum Hall regime with a scanning single electron transistor [11]. Our microscopic approach provides direct insight into the nature of localization. Surprisingly, despite strong disorder, our findings indicate that localization in graphene is not dominated by single particle physics, but rather by a competition between the underlying disorder potential and the repulsive Coulomb interaction responsible for screening.Comment: 18 pages, including 5 figure