Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Background: Nonadherence is very common among subjects undergoing pharmacotherapy for schizophrenia and depression. This study aimed to evaluate the performance of the ratio of the nonlinear mixed effects pharmacokinetic model predicted concentration to observed drug concentration (ratio of population predicted to observed concentration (Cpred/Cobs) and ratio of individual predicted to observed concentration (Cipred/Cobs) as a measure of erratic drug exposure, driven primarily by variable execution of the dosage regimen and unknown true dosage history. Methods: Modeling and simulation approaches in conjunction with dosage history information from the Medication Event Monitoring System (MEMS, provided by the "Depression: The search for treatment relevant phenotypes" study), was applied to evaluate the consistency of exposure via simulation studies with scenarios representing a long half-life drug (escitalopram). Adherence rates were calculated based on the percentage of the prescribed doses actually taken correctly during the treatment window of interest. The association between Cpred/Cobs, Cipred/Cobs ratio, and adherence rate was evaluated under various assumptions of known dosing history. Results: Simulations for those scenarios representing a known dosing history were generated from historical MEMS data. Simulations of a long half-life drug exhibited a trend for overprediction of concentrations in patients with a low percentage of doses taken and underprediction of concentrations in patients taking more than their prescribed number of doses. Overall, the ratios did not predict adherence well, except when the true adherence rates were extremely high (greater than 100% of prescribed doses) or extremely low (complete nonadherence). In general, the Cipred/Cobs ratio was a better predictor of adherence rate than the Cpred/Cobs ratio. Correct predictions of extreme (high, low) 7-day adherence rates using Cipred/Cobs were 73.8% and 64.0%. Conclusion: This simulation study demonstrated the limitations of the Cpred/obs and Cipred/obs ratios as metrics for actual dosage intake history, and identified that use of MEMS dosing history monitoring combined with sparse pharmacokinetic sampling is a more reliable approach. © 2011 Feng et al

Sr, Nd Pb isotopic characteristics of granulite and pyroxenite xenoliths in Hannuoba basalts, Hebei Province, and their implications for geologic processes

Rb-Sr, Sm-Nd and Pb isotopic systematics are reported for granulite and pyroxenite xenoliths in Hannuoba basalts, Hebei Province. The isotopic characteristics of xenoliths suggest t hat they might have formed recently , although there is no strict constraint on the precise age. The decoupling of low Rb/Sr and high [87]Sr/[86]Sr ratios implies the multi-stage evolution history and strong mixing processes. There are close ties between granulite and pyroxenites with different mineral assemblages on the Sr-Nd, Pb-Sr and Pb-Nd correlation figures. The granulite is the common end-member o f the three kinds o f pyroxenite. Combined with the distribution of the xenoliths in space and their isotopic relationships, It is proposed that delamination can be well used to explain the ties.系统研究了河北汉诺坝玄武岩中二辉麻粒岩和辉石岩捕虏体的Sr、Nd、Pb 同位素特征。虽然未确定捕虏体的形成时代, 但同位素特征显示它们可能为较近期( 中生代以来) 形成。低的Rb/Sr 与高 的[87]Sr/[86]Sr 比值的解耦表明捕虏体的形成经历了较强的混合作用。在二元同位素相关图上, 三类具不同矿物组成的辉石岩与二辉麻粒岩有密切关系, 即二辉麻粒岩投点位置是三类辉石岩的共同端点。综合考虑捕虏体的空间分布及其在Sr 、Nd、Pb 同位素协变图上的关系, 可以认为层离作用可较好地解释这些现象。published_or_final_versio

下地壳及壳慢过渡带化学不均一性 -- 河北汉诺坝地区深源捕虏体元素地球化学证据

河北汉诺坝玄武岩中长英质麻粒岩、镁铁质麻粒岩和辉石岩捕虏体的主量元素和微量元素特征, 反映了下地壳及壳鳗过渡带组成具有高度化学不均一性。不相容元素原始地慢标准化曲线特征的差异表明捕虏体成因复杂。MgO 与不相容元素无或仅有很弱的相关性, 与相容元素的相关性则相对较明显。这些特征反映了下地壳及壳慢过渡带存在较强和多元的混合作用。捕虏体的加权平均值比基于麻粒岩地体资料估算的下地壳平均组成偏基性, 揭示了二者可能的成因差异。The major and trace element data of granulite and pyroxenite xenoliths, which are entrained in Hannuoba basalt Hebei Province, North China, suggest the highly chemical heterogeneity in the lower crust and crust-mantle transitional zone. There is no or only POor linear correlation between MgO and incompatible elements. Whereas a bit remarked correlations are observed between MgO and most compatible elements.The geochemical characteristics suggest that the strong and multiple mixing processes may have Occurred universally both in the lower crust and crust-mantle transitional zone. The weighed average composition of xenoliths shows a more mafic composition of the lower crust than that estimated from granulite data, which may imply the difference in the genesis.published_or_final_versio

Ear-clipping Based Algorithms of Generating High-quality Polygon Triangulation

A basic and an improved ear clipping based algorithm for triangulating simple polygons and polygons with holes are presented. In the basic version, the ear with smallest interior angle is always selected to be cut in order to create fewer sliver triangles. To reduce sliver triangles in further, a bound of angle is set to determine whether a newly formed triangle has sharp angles, and edge swapping is accepted when the triangle is sharp. To apply the two algorithms on polygons with holes, "Bridge" edges are created to transform a polygon with holes to a degenerate polygon which can be triangulated by the two algorithms. Applications show that the basic algorithm can avoid creating sliver triangles and obtain better triangulations than the traditional ear clipping algorithm, and the improved algorithm can in further reduce sliver triangles effectively. Both of the algorithms run in O(n2) time and O(n) space.Comment: Proceedings of the 2012 International Conference on Information Technology and Software Engineering Lecture Notes in Electrical Engineering Volume 212, 2013, pp 979-98

Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Negative Effect of Smoking on the Performance of the QuantiFERON TB Gold in Tube Test.

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status

Contributions of residential coal combustion to the air qualityin Beijing–Tianjin–Hebei (BTH), China: a case study

In the present study, the WRF-Chem model is used to assess contributions of residential coal combustion (RCC) emissions to the air quality in Beijing-Tianjin-Hebei (BTH) during a persistent air pollution episode from 9 to 25 January 2014. In general, the predicted temporal variations and spatial distributions of the mass concentrations of air pollutants are in good agreement with observations at monitoring sites in BTH. The WRF-Chem model also reasonably reproduces the temporal variations in aerosol species when compared with the aerosol mass spectrometer measurements in Beijing. The RCC emissions play an important role in the haze formation in BTH, contributing about 23.1% of PM2.5 (fine particulate matter) and 42.6% of SO2 during the simulation period on average. Organic aerosols dominate the PM2.5 from the RCC emissions in BTH, with a contribution of 42.8 %, followed by sulfate (17.1 %). The air quality in Beijing is remarkably improved when the RCC emissions in BTH and the surrounding areas are excluded in model simulations, with a 30% decrease in PM2.5 mass concentrations. However, if only the RCC emissions in Beijing are excluded, the local PM2.5 mass concentration is decreased by 18.0% on average. Our results suggest that the implementation of the residential coal replacement by clean energy sources in Beijing is beneficial to the local air quality. Should residential coal replacement be carried out in BTH and its surrounding areas, the air quality in Beijing would be improved remarkably. Further studies would need to consider uncertainties in the emission inventory and meteorological fields

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Solitary waves in the Nonlinear Dirac Equation

In the present work, we consider the existence, stability, and dynamics of solitary waves in the nonlinear Dirac equation. We start by introducing the Soler model of self-interacting spinors, and discuss its localized waveforms in one, two, and three spatial dimensions and the equations they satisfy. We present the associated explicit solutions in one dimension and numerically obtain their analogues in higher dimensions. The stability is subsequently discussed from a theoretical perspective and then complemented with numerical computations. Finally, the dynamics of the solutions is explored and compared to its non-relativistic analogue, which is the nonlinear Schr{\"o}dinger equation. A few special topics are also explored, including the discrete variant of the nonlinear Dirac equation and its solitary wave properties, as well as the PT-symmetric variant of the model