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

Effects of Lateral Diffusion on the Dynamics of Desorption

The adsorbate dynamics during simultaneous action of desorption and lateral adsorbate diffusion is studied in a simple lattice-gas model by kinetic Monte Carlo simulations. It is found that the action of the coverage-conserving diffusion process during the course of the desorption has two distinct, competing effects: a general acceleration of the desorption process, and a coarsening of the adsorbate configuration through Ostwald ripening. The balance between these two effects is governed by the structure of the adsorbate layer at the beginning of the desorption process

The effect of temperature on the rate of development and emergence of schistosome cercariae

Zoologica Africana 2(2): 211-22

The early ontogeny of the Columella auris of Crocodilus niloticus and its bearing on problems concerning the upper end of the reptilian hyoid arch

No Abstract

Sampling constrained probability distributions using Spherical Augmentation

Statistical models with constrained probability distributions are abundant in machine learning. Some examples include regression models with norm constraints (e.g., Lasso), probit, many copula models, and latent Dirichlet allocation (LDA). Bayesian inference involving probability distributions confined to constrained domains could be quite challenging for commonly used sampling algorithms. In this paper, we propose a novel augmentation technique that handles a wide range of constraints by mapping the constrained domain to a sphere in the augmented space. By moving freely on the surface of this sphere, sampling algorithms handle constraints implicitly and generate proposals that remain within boundaries when mapped back to the original space. Our proposed method, called {Spherical Augmentation}, provides a mathematically natural and computationally efficient framework for sampling from constrained probability distributions. We show the advantages of our method over state-of-the-art sampling algorithms, such as exact Hamiltonian Monte Carlo, using several examples including truncated Gaussian distributions, Bayesian Lasso, Bayesian bridge regression, reconstruction of quantized stationary Gaussian process, and LDA for topic modeling.Comment: 41 pages, 13 figure

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

Introducing a new breed of wine yeast: interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast and Saccharomyces mikatae

Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment.Jennifer R. Bellon, Frank Schmid, Dimitra L. Capone, Barbara L. Dunn, Paul J. Chamber

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT