Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Intravenous lidocaine infusion as a component of multimodal analgesia for colorectal surgery-measurement of plasma levels

Abstract Background Growing evidence suggests that intravenous lidocaine as a component of multimodal analgesia improves recovery after major colorectal surgery. There is little published data regarding ideal dosing and target plasma concentration in this context, and we wanted to establish our dosing schedule was safe by measuring blood levels of lidocaine. Methods We measured the plasma lidocaine concentration of 32 patients at 30 min, 6 h and 12 h after starting intravenous lidocaine infusion for analgesia after major colorectal surgery. Patients received a bolus of 1.5 mg kg−1 over 20 min at the time of induction of anaesthesia. This was followed by a continuous infusion of 2% w/v lidocaine at 3 ml hr−1 (60 mg hr−1) for patients weighing up to 70 kg and 6 ml hr−1 (120 mg hr−1) for patients weighing over 70 kg, using actual body weight. Results The overall mean plasma lidocaine concentration was 4.0 μg ml−1 (range 0.6–12.3 μg ml−1). In patients treated with the higher infusion dose, the mean concentration was 4.6 μg ml−1 compared to 3.2 μg ml−1 in those patients on the lower dose. Mean levels were higher at 6 h than 30 min and higher again at 12 h. There were no adverse events or reports of symptoms of local anaesthetic toxicity. Conclusions Whilst there were no signs or symptoms of lidocaine toxicity in our patients, there was a wide range of plasma concentrations including some over 10 μg ml−1; a level above which symptoms of toxicity may be expected. We have changed our dosing protocol to using ideal rather than actual body weight based on these results

Fermi surface and quasiparticle dynamics of Na(x)CoO2 {x=0.7} investigated by Angle-Resolved Photoemission Spectroscopy

We present an angle-resolved photoemission study of Na0.7CoO2, the host cobaltate of the NaxCoO2.yH2O series. Our results show a large hexagonal-like hole-type Fermi surface, an extremely narrow strongly renormalized quasiparticle band and a small Fermi velocity. Along the Gamma to M high symmetry line, the quasiparticle band crosses the Fermi level from M toward Gamma consistent with a negative sign of effective single-particle hopping (t ): t is estimated to be about 8 meV which is on the order of exchange coupling J in this system. This suggests that t ~ J ~ 10 meV is an important energy scale in the system. Quasiparticles are well defined only in the T-linear resistivity regime. Small single particle hopping and unconventional quasiparticle dynamics may have implications for understanding the unusual behavior of this new class of compounds.Comment: Revised text, Added Figs, Submitted to PR

Curie Temperatures for Three-Dimensional Binary Ising Ferromagnets

Using the Swendsen and Wang algorithm, high accuracy Monte Carlo simulations were performed to study the concentration dependence of the Curie temperature in binary, ferromagnetic Ising systems on the simple-cubic lattice. Our results are in good agreement with known mean-field like approaches. Based on former theoretical formulas we propose a new way of estimating the Curie temperature of these systems.Comment: nr. of pages:13, LATEX. Version 2.09, Scientific Report :02/1994 (Univ. of Bergen, Norway), 7 figures upon reques

Spatial structure increases the waiting time for cancer

Cancer results from a sequence of genetic and epigenetic changes which lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells, and thus, to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been experiencing increasing interest in recent years. Many efforts have been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. We propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to asses two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones, decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale, determined here. These characteristic features of clonal interference may help to predict the onset of cancers with pronounced spatial structure and to interpret spatially-sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progressing colon cancer, and possibly other cancers where spatial structure matters.Comment: 21 page

Charge Fluctuations in Geometrically Frustrated Charge Ordering System

Effects of geometrical frustration in low-dimensional charge ordering systems are theoretically studied, mainly focusing on dynamical properties. We treat extended Hubbard models at quarter-filling, where the frustration arises from competing charge ordered patterns favored by different intersite Coulomb interactions, which are effective models for various charge transfer-type molecular conductors and transition metal oxides. Two different lattice structures are considered: (a) one-dimensional chain with intersite Coulomb interaction of nearest neighbor V_1 and that of next-nearest neighbor V_2, and (b) two-dimensional square lattice with V_1 along the squares and V_2 along one of the diagonals. From previous studies, charge ordered insulating states are known to be unstable in the frustrated region, i.e., V_1 \simeq 2V_2 for case (a) and V_1 \simeq V_2 for case (b), resulting in a robust metallic phase even when the interaction strenghs are strong. By applying the Lanczos exact diagonalization to finite-size clusters, we have found that fluctuations of different charge order patterns exist in the frustration-induced metallic phase, showing up as characteristic low energy modes in dynamical correlation functions. Comparison of such features between the two models are discussed, whose difference will be ascribed to the dimensionality effect. We also point out incommensurate correlation in the charge sector due to the frustration, found in one-dimensional clusters.Comment: 8 pages, 9 figure