PLASMA CONCENTRATIONS OF METHADONE DURING POSTOPERATIVE PATIENT-CONTROLLED EXTRADURAL ANALGESIA

Plasma concentrations of methadone were measured by gas chromatography in 16 patients receiving extradural methadone by continuous infusion for relief of postoperative pain. Venous blood samples were taken after a loading dose of extradural methadone 2 mg and during infusion of 0.46 mg h−1 plus patient-controlled increments of 0.2-1 mg. Mean (SD) plasma concentration of methadone was 9.8 (2.1) ng ml−1 at 15 min; this did not change significantly during the first 2 h, after which it increased gradually to 32.2 (4.6) ng ml−1 (P < 0.001) at the end of 24 h. The mean quantity of extradural methadone required to produce effective analgesia was 10.3 (1.8) mg during the first 12 h after operation and 6 (1.0) mg for the subsequent 12 h. The mean amount of methadone for effective analgesia on the second day was 7.6 (1.1) mg. No adverse effects were detected during the 2-3 days of methadone therapy. Plasma concentration of methadone increased significantly during patient-controlled infusion of extradural methadone in the first 24 h after operation, suggesting rapid vascular uptake. Systemic activity of the drug contributes to the analgesic effect of extradural methadon

Giant crystal-electric-field effect and complex magnetic behavior in single-crystalline CeRh3Si2

Single-crystalline CeRh3Si2 was investigated by means of x-ray diffraction, magnetic susceptibility, magnetization, electrical resistivity, and specific heat measurements carried out in wide temperature and magnetic field ranges. Moreover, the electronic structure of the compound was studied at room temperature by cerium core-level x-ray photoemission spectroscopy (XPS). The physical properties were analyzed in terms of crystalline electric field and compared with results of ab-initio band structure calculations performed within the density functional theory approach. The compound was found to crystallize in the orthorhombic unit cell of the ErRh3Si2 type (space group Imma -- No.74, Pearson symbol: oI24) with the lattice parameters: a = 7.1330(14) A, b = 9.7340(19) A, and c = 5.6040(11) A. Analysis of the magnetic and XPS data revealed the presence of well localized magnetic moments of trivalent cerium ions. All physical properties were found to be highly anisotropic over the whole temperature range studied, and influenced by exceptionally strong crystalline electric field with the overall splitting of the 4f1 ground multiplet exceeding 5700 K. Antiferromagnetic order of the cerium magnetic moments at TN = 4.70(1)K and their subsequent spin rearrangement at Tt = 4.48(1) K manifest themselves as distinct anomalies in the temperature characteristics of all investigated physical properties and exhibit complex evolution in an external magnetic field. A tentative magnetic B-T phase diagram, constructed for B parallel to the b-axis being the easy magnetization direction, shows very complex magnetic behavior of CeRh3Si2, similar to that recently reported for an isostructural compound CeIr3Si2. The electronic band structure calculations corroborated the antiferromagnetic ordering of the cerium magnetic moments and well reproduced the experimental XPS valence band spectrum.Comment: 32 pages, 12 figures, to appear in Physical Review

Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well

Scaling analysis of the magnetic monopole mass and condensate in the pure U(1) lattice gauge theory

We observe the power law scaling behavior of the monopole mass and condensate in the pure compact U(1) gauge theory with the Villain action. In the Coulomb phase the monopole mass scales with the exponent \nu_m=0.49(4). In the confinement phase the behavior of the monopole condensate is described with remarkable accuracy by the exponent \beta_{exp}=0.197(3). Possible implications of these phenomena for a construction of a strongly coupled continuum U(1) gauge theory are discussed.Comment: Added references [1

The Impact of Olfactory Disorders in the United Kingdom

Olfactory disorders are believed to affect 5% of the general population and have been shown to bear significant psychosocial consequences to sufferers. Although more common than blindness and profound deafness in the United Kingdom, the impact of these disorders has not been assessed to date and the plight of British patients has yet to be quantified. In 2012, a patient support organization, Fifth Sense, was founded to provide information and support to sufferers of chemosensory disorders. Following a recent members conference, a survey of the membership was conducted anonymously using a series of questions based on an existing olfactory disorders questionnaire. From 496 respondents, this has demonstrated high rates of depression (43%) and anxiety (45%), impairment of eating experience (92%), isolation (57%), and relationship difficulties (54%). Women appear to have significantly more issues than men in terms of social and domestic dysfunction relating to olfactory loss (P = 0.01). Qualitative disorders also affected more than 1 in 5 members with parosmia reported in 19% and phantosmia in 24%. This paper discusses the details of the British story of anosmia and other related disorders as depicted by those most affected

Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival.

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p &lt; 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure

On practical problems to compute the ghost propagator in SU(2) lattice gauge theory

In SU(2) lattice pure gauge theory we study numerically the dependence of the ghost propagator G(p) on the choice of Gribov copies in Lorentz (or Landau) gauge. We find that the effect of Gribov copies is essential in the scaling window region, however, it tends to decrease with increasing beta. On the other hand, we find that at larger beta-values very strong fluctuations appear which can make problematic the calculation of the ghost propagator.Comment: 15 pages, 5 postscript figures. 2 Figures added Revised version as to be published in Phys.Rev.

Nonperturbative late time asymptotics for heat kernel in gravity theory

Recently proposed nonlocal and nonperturbative late time behavior of the heat kernel is generalized to curved spacetimes. Heat kernel trace asymptotics is dominated by two terms one of which represents a trivial covariantization of the flat-space result and another one is given by the Gibbons-Hawking integral over asymptotically-flat infinity. Nonlocal terms of the effective action generated by this asymptotics might underly long- distance modifications of the Einstein theory motivated by the cosmological constant problem. New mechanisms of the cosmological constant induced by infrared effects of matter and graviton loops are briefly discussed.Comment: 22 pages, LaTeX, final version, to be published in Phys. Rev.

Processing Succinct Matrices and Vectors

We study the complexity of algorithmic problems for matrices that are represented by multi-terminal decision diagrams (MTDD). These are a variant of ordered decision diagrams, where the terminal nodes are labeled with arbitrary elements of a semiring (instead of 0 and 1). A simple example shows that the product of two MTDD-represented matrices cannot be represented by an MTDD of polynomial size. To overcome this deficiency, we extended MTDDs to MTDD_+ by allowing componentwise symbolic addition of variables (of the same dimension) in rules. It is shown that accessing an entry, equality checking, matrix multiplication, and other basic matrix operations can be solved in polynomial time for MTDD_+-represented matrices. On the other hand, testing whether the determinant of a MTDD-represented matrix vanishes PSPACE$-complete, and the same problem is NP-complete for MTDD_+-represented diagonal matrices. Computing a specific entry in a product of MTDD-represented matrices is #P-complete.Comment: An extended abstract of this paper will appear in the Proceedings of CSR 201