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- Ji, Shuangmin, et al.
(författare)
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Population pharmacokinetic-pharmacodynamic (PopPK/PD) modeling of risperidone and its active metabolite in Chinese schizophrenia patients
- 2016
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Ingår i: International journal of clinical pharmacology and therapeutics. - 0946-1965. ; 54:5, s. 378-389
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Risperidone is a second-generation antipsychotic agent commonly used in the treatment of 31.1% of schizophrenia patients in China, it is the most commonly-prescribed antipsychotic agent. Despite the abundant use of risperidone, population pharmacokinetic-pharmacodynamic models of risperidone have not been performed in Chinese schizophrenia patients. The objective of this study was to develop a population pharmacokinetic-pharmacodynamic (PopPK/PD) model to describe the PK behavior and efficacy of risperidone and 9-hydroxy-risperidone (active metabolite) in Chinese patients. Methods: Plasma concentration data (702 measurements from 131 patients) and positive and negative syndrome scale (PANSS) scores (258 observations from 56 patients) were analyzed using a nonlinear mixed-effects modeling (NONMEM) approach with first-order conditional estimation with interaction (FOCEI). The influence of potential covariates was evaluated. Model robustness was assessed using external validation, nounalized prediction distribution error, nonparametric bootstrap, and visual predictive check approaches. Results: Risperidone concentration data were well described by a one-compartmental model incorporating an additional compartment that refers to the concentration profiles of 9-hydroxy-risperidone. A complex absorption procedure was incorporated into the model to describe the metabolism of risperidone to 9-hydroxy-risperidone in the gastrointestinal (GI) tract. A binomial distribution in the estimated clearance (CL) of risperidone has been identified in our model. Decrease in PANSS score along with total AUC (AUC(total)) of risperidone and 9-hydroxy-risperidone was best characterized by an E-max model with 3 transit compartments describing the delay of drug effect. Conclusions: Considerable differences in PK behavior and drug effect of risperidone have been identified among Chinese extensive metabolizing (EM) and poor metabolizing (PM) patients. This PopPK/PD model may fulfill individualized treatment in clinical practice and may potentially be transferred to other antipsychotic therapies.
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2. |
- Hanna, Nada, et al.
(författare)
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Presence of antibiotic residues in various environmental compartments of Shandong province in eastern China: Its potential for resistance development and ecological and human risk
- 2018
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Ingår i: Environment International. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0160-4120 .- 1873-6750. ; 114, s. 131-142
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the occurrence of antibiotic residues in different types of environmental samples including water samples in rural Shandong province, China. Further, to characterize the potential ecological risk for development of antibiotic resistance in the environment, and the potential direct human health risk of exposure to antibiotics via drinking water and vegetables. Methods: Environmental samples (n = 214) (river water, waste water, drinking water, sediments, manure, soil and edible parts of vegetables) were collected in twelve villages in Shandong province in eastern China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentration of antibiotic residues. The ratio of the measured environmental concentrations (MEC) to the predicted no-effect concentrations (PNEC) was used to evaluate the ecological risk (risk quotient, RQ) for development of antibiotic resistance. The potential risks to human health through exposure to antibiotics in drinking water were assessed by comparing measured environmental concentrations (MEC) and predicted no-effect concentration in drinking water (PNECDW), and in vegetables by comparing estimated daily intake (EDI) to ADI. Results: Sulfapyridine, sulfamethoxazole, ciprofloxacin, enrofloxacin, levofloxacin, norfloxacin, chloramphenicol, florfenicol, doxycycline, and metronidazole were detected at concentrations ranging between 0.3 and 3.9 ng/L in river water, 1.3 and 12.5 ng/L in waste water, 0.5 and 21.4 ng/L in drinking water, 0.31 and 1.21 mu g/kg in river sediment, 0.82 and 1.91 mu g/kg in pig manure, 0.1 and 11.68 mu g/kg in outlet sediment, 0.5 and 2.5 mu g/kg in soil, and 6.3 and 27.2 mu g/kg in vegetables. The RQs for resistance development were amp;gt; 1 for enrofloxacin, levofloxacin, and ranged between 0.1 and 1 for ciprofloxacin. MECs/PNECDW ratios were amp;lt; 1 from exposure to antibiotics through drinking water for both adults and children. EDI/ADI ratios were amp;lt; 0.1 from exposure to antibiotics by vegetable consumption. Conclusions: Antibiotic pollutants were ubiquitous in various environmental compartments of Shandong province of China. Risk estimates indicated a potential for the measured levels of enrofloxacin, levofloxacin and ciprofloxacin in waste water to pose an ecological risk for resistance selection, and further studies are needed to validate this finding. The investigated antibiotics did not appear to pose an appreciable direct human health risk from environmental exposure through drinking water or vegetables consumption. However, they might still pose a risk for resistance development.
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3. |
- Lu, Qinghua, et al.
(författare)
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MapReduce Job Optimization : A Mapping Study
- 2016
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Ingår i: Proceedings - 2015 International Conference on Cloud Computing and Big Data, CCBD 2015. - 9781467383509 ; , s. 81-88
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Konferensbidrag (refereegranskat)abstract
- MapReduce has become the standard model for supporting big data analytics. In particular, MapReduce job optimization has been widely considered to be crucial in the implementations of big data analytics. However, there is still a lack of guidelines especially for practitioners to understand how the MapReduce jobs can be optimized. This paper aims to systematic identify and taxonomically classify the existing work on job optimization. We conducted a mapping study on 47 selected papers that were published between 2004 and 2014. We classified and compared the selected papers based on a 5WH-based characterization framework. This study generates a knowledge base of current job optimization solutions and also identifies a set of research gaps and opportunities. This study concludes that job optimization is still in an early stage of maturity. More attentions need to be paid to the cross-data center, cluster or rack job optimization to improve communication efficiency.
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