This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature ...is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype‐guided warfarin dosing to achieve a target international normalized ratio of 2–3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
This paper investigates the effectiveness of sensorless operation in carrier-signal-injection-based sensorless-control methods for permanent-magnet brushless ac motors. The sensorless safety ...operation area (SSOA) is introduced with due account for the quantization error in the analog to digital conversion. The SSOA defines a working area in the d - q plane in which the motor can operate in sensorless mode with a guaranteed performance in steady state. With the aid of SSOA, a proper injected carrier signal can be selected for the specific prototype machine and current-measurement resolution. Experimental results confirm that the performance of sensorless operation can be guaranteed when the machine operates inside the SSOA with cross-saturation compensation.
In this article, an adaptive linear neuron based current harmonics suppression method for permanent magnet synchronous motors with nonsinusoidal back electromotive force (EMF) is presented, with due ...account for dead-time effect. The current harmonics can be well-suppressed by feedforwarding a self-tuning compensation voltage. The proposed method does not rely on the knowledge of back-EMF harmonic components and dead-time effect. Moreover, the proposed method is easy to implement, since it does not need the process to extract the current harmonics. The effectiveness of the proposed method is verified by both simulation and experimental results without requiring additional hardware.
AbstractObjectiveTo derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. MethodsRespondents from the US adult ...population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. ResultsOf 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from −0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). ConclusionsA societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.
The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects, curates, and disseminates information about the impact of human genetic variation on drug responses. It provides clinically ...relevant information, including dosing guidelines, annotated drug labels, and potentially actionable gene–drug associations and genotype–phenotype relationships. Curators assign levels of evidence to variant–drug associations using well‐defined criteria based on careful literature review. Thus, PharmGKB is a useful source of high‐quality information supporting personalized medicine–implementation projects.
Clinical Pharmacology & Therapeutics (2012); 92 4, 414–417. doi:10.1038/clpt.2012.96
Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding single‐nucleotide polymorphism, rs4149056T>C, in SLCO1B1 increases systemic exposure to ...simvastatin and the risk of muscle toxicity. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for simvastatin based on SLCO1B1 genotype. This article is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin‐induced myopathy.
Clinical Pharmacology & Therapeutics (2014); 96 4, 423–428. doi:10.1038/clpt.2014.125
ABSTRACT
This study was conducted to investigate the effect of nano-selenium (nano-Se) on performance, meat quality, immune function, oxidation resistance, and tissue selenium content in broilers. A ...total of five hundred forty 1-d-old male Arbor Acres broilers were randomly allotted to 1 of 5 treatments with each treatment being applied to 6 replicates of 18 chicks. The 5 treatments consisted of corn-soybean meal-based diets supplemented with 0.0, 0.3, 0.5, 1.0, or 2.0 mg/kg of nano-Se. The selenium content of the unsupplemented control diet was 0.09 mg/kg for the starter phase (0 to 21 d) and 0.08 mg/kg for the grower phase (22 to 42 d). There were no significant differences (P > 0.05) in performance, meat color, or immune organ index (thymus, bursa, and spleen) due to supplementation with nano-Se. On d 42, a significant quadratic effect of nano-Se was observed on glutathione peroxidase activity, free radical inhibition, contents of IgM, glutathione, and malondialdehyde in serum, on glutathione peroxidase activity, free radical inhibition in liver, and on glutathione peroxidase activity in muscle, with birds fed 0.30 mg/kg of nano-Se exhibiting the best effect and birds fed 2.0 mg/kg of nano-Se showing the worst effect on these parameters. Liver and muscle selenium content increased linearly and quadratically as the dietary nano-Se level increased (P < 0.01), and reached the highest value when 2.0 mg/kg of nano-Se was fed. Based on a consideration of all experiment indexes, 0.3 to 0.5 mg/kg is suggested to be the optimum level of supplementation of nano-Se, and the maximum supplementation of nano-Se could not be more than 1.0 mg/kg in broilers.
A parameterization of a sea‐salt source function for both sub‐ and super‐micron particles was developed based on the semi‐empirical formulation of Monahan et al. 1986. This new parameterization ...extends the range of Monahan's equation to below 0.2 μm in diameter where it has been found to overestimate submicron sea‐salt aerosols, especially the sea‐salt number concentrations. The new parameterization was used in a one‐dimensional (1‐D) column model to predict the number size distributions and compared with reasonable agreement to the observed distributions at various wind speeds reported by O'Dowd et al. 1997. A global 3‐D sea‐salt simulation with this parameterization was also made and a much better dependence of sea‐salt on surface wind speed was predicted than other schemes compared to observations. For an indirect impact assessment of sea‐salt aerosols on climate where submicron particles may have a dominant contribution to aerosol‐cloud interactions, this scheme provides the most realistic number flux of sea‐salt particles between ocean and atmosphere.
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