Contributions to an improved phenytoin monitoring and dosing in hospitalized patients

Phenytoin (PHT) is one of the mostly used and well established anticonvulsants for the treatment of epilepsy and a standard in the antiepileptic prophylaxis in adults with severe traumatic brain injuries before and after neurosurgical intervention. Its therapeutic use is challenging as PHT has a narrow therapeutic range and shows non-linear kinetics. It is extensively metabolized by a variety of CYP enzymes. PHT shows 85-95% binding to plasma proteins mostly albumin. This renders PHT also an important drug interaction candidate. Therefore, therapeutic drug monitoring is often required. A rational timing for good interpretation of the lab data translated in optimal individual dosing are necessary. Therapeutic guidance especially in teaching hospitals are needed and have to be implemented. Bayesian Forecasting (BF) versus conventional dosing (CD): a retrospective, long-term, single centre analysis In the hospital, medication management for effective antiepileptic therapy with PHT often needs rapid IV loading and subsequent dose adjustment according to TDM. To investigate PHT performance in reaching therapeutic target serum concentration, a BF regimen was compared to CD, according to the official summary of product characteristics. In a Swiss acute care teaching hospital (Kantonsspital Aarau), a retrospective, single centre, and long-term analysis was assessed by using all PHT serum tests from the central lab from 1997 to 2007. The BF regimen consisted of a guided, body weight-adapted rapid IV PHT loading over five days with pre-defined TDM time points. The CD was applied without written guidance. Assuming non-normally distributed data, non-parametric statistical methods were used. A total of 6’120 PHT serum levels (2’819 BF and 3’301 CD) from 2’589 patients (869 BF and 1’720 CD) were evaluated and compared. 63.6% of the PHT serum levels from the BF group were within the therapeutic range versus only 34.0% in the CD group (p<0.0001). The mean BF serum level was 52.0 ± 22.1 µmol/L (within target range), whereas the mean serum level of the CD was 39.8 ± 28.2 µmol/L (sub-target range). In the BF group, men had small but significantly lower PHT serum levels compared to women (p<0.0001). The CD group showed no significant gender difference (p=0.187). A comparative sub-analysis of age-related groups (children, adolescents, adults, seniors, and elderly) showed significant lower target levels (p<0.0001) for each group in the CD group, compared to BF. Comparing the two groups, BF showed significantly better performance in reaching therapeutic PHT serum levels. Free PHT assessment However, total serum drug levels of difficult-to-dose drugs like PHT are sometimes insufficient. The knowledge of the free fraction is necessary for correct dosing. In a subgroup analysis of the above BF vs. CD study we evaluated the suitability of the Sheiner-Tozer algorithm to calculate the free PHT fraction in hypoalbuminemic patients. Free PHT serum concentrations were calculated from total PHT concentration in hypoalbuminemic patients and compared with the measured free PHT. The patients were separated into two groups (a low albumin group; 35 ≤ albumin ≥ 25 g/L and a very low albumin group; albumin < 25 g/L). These two groups were compared and statistically analysed for the calculated and the measured free PHT concentration. The calculated (1.2 mg/L, SD=0.7) and the measured (1.1 mg/L, SD=0.5) free PHT concentration correlated. The mean difference in the low and the very low albumin group was 0.10 mg/L (SD=1.4, n=11) and 0.13 mg/L (SD=0.24, n=12), respectively. Although the variability of the data could be a bias, no statistically significant difference between the groups was found: t-test (p=0.78), the Passing-Bablok regression, the Spearman’s rank correlation coefficient of r=0.907 and p=0.00, and the Bland-Altman plot including the regression analysis between the calculated and the measured value (M=0.11, SD=0.28). We concluded that in absence of a free PHT serum concentration measurement also in hypoalbuminemic patients, the Sheiner-Tozer algorithm represents a useful tool to assist TDM to calculate or control free PHT by using total PHT and the albumin concentration. GC-MS Analysis of biological PHT samples To correlate PHT blood serum levels, with “brain PHT levels” (the site of action of PHT), extracellular fluid from microdialysates in neurosurgical patients could be analyzed for PHT by an appropriate quantifying analytical method. In this investigation we describe the development and validation of a sensitive gas chromatography–mass spectrometry (GC–MS) method to identify and quantitate PHT in brain microdialysate, saliva and blood from human samples. For sample clean-up a SPE was performed with a nonpolar C8-SCX column. The eluate was evaporated with nitrogen (50°C) and derivatized with trimethylsulfonium hydroxide before GC-MS analysis. 5-(p-methylphenyl)-5-phenylhydantoin was used as internal standard. The MS was run in scan mode and the identification was made with three ion fragment masses. All peaks were identified with MassLib. Spiked PHT samples showed recovery after SPE of ≥ 94%. The calibration curve (PHT 50 to 1’200 ng/ml, n=6 at six concentration levels) showed good linearity and correlation (r2 > 0.998). The limit of detection was 15 ng/mL, the limit of quantification was 50 ng/mL. Dried extracted samples were stable within a 15% deviation range for ≥ 4 weeks at room temperature. The method met International Organization for Standardization standards and was able to detect and quantify PHT in different biological matrices and patient samples. The GC-MS method with SPE is specific, sensitive, robust and well reproducible and therefore, an appropriate candidate for pharmacokinetic assessment of PHT concentrations in different biological samples of treated patients

A survey on OFDM-based elastic core optical networking

Orthogonal frequency-division multiplexing (OFDM) is a modulation technology that has been widely adopted in many new and emerging broadband wireless and wireline communication systems. Due to its capability to transmit a high-speed data stream using multiple spectral-overlapped lower-speed subcarriers, OFDM technology offers superior advantages of high spectrum efficiency, robustness against inter-carrier and inter-symbol interference, adaptability to server channel conditions, etc. In recent years, there have been intensive studies on optical OFDM (O-OFDM) transmission technologies, and it is considered a promising technology for future ultra-high-speed optical transmission. Based on O-OFDM technology, a novel elastic optical network architecture with immense flexibility and scalability in spectrum allocation and data rate accommodation could be built to support diverse services and the rapid growth of Internet traffic in the future. In this paper, we present a comprehensive survey on OFDM-based elastic optical network technologies, including basic principles of OFDM, O-OFDM technologies, the architectures of OFDM-based elastic core optical networks, and related key enabling technologies. The main advantages and issues of OFDM-based elastic core optical networks that are under research are also discussed

Ono: an open platform for social robotics

In recent times, the focal point of research in robotics has shifted from industrial ro- bots toward robots that interact with humans in an intuitive and safe manner. This evolution has resulted in the subfield of social robotics, which pertains to robots that function in a human environment and that can communicate with humans in an int- uitive way, e.g. with facial expressions. Social robots have the potential to impact many different aspects of our lives, but one particularly promising application is the use of robots in therapy, such as the treatment of children with autism. Unfortunately, many of the existing social robots are neither suited for practical use in therapy nor for large scale studies, mainly because they are expensive, one-of-a-kind robots that are hard to modify to suit a specific need. We created Ono, a social robotics platform, to tackle these issues. Ono is composed entirely from off-the-shelf components and cheap materials, and can be built at a local FabLab at the fraction of the cost of other robots. Ono is also entirely open source and the modular design further encourages modification and reuse of parts of the platform

Improving productivity in tropical lakes and reservoirs

Freshwater aquaculture, Inland fisheries

Field testing of an onsite sanitation system on apartment building blackwater using biological treatment and electrochemical disinfection

The Closed Loop Advanced Sanitation System (CLASS) was designed to treat, disinfect, and recycle toilet blackwater from existing flush toilets in a multi-story apartment building. Two systems were tested at two unique sites in Coimbatore, India for a combined 7500+ treatment hours resulting in more than 180 000 L of treated water. The CLASS prototypes used a combination of biological pretreatment and electrochemical oxidation processes to produce treated water that nearly met the stringent requirements outlined in the standard ISO 30500. The nutrient and organic loading from the toilet blackwater was predominantly reduced by over 85–95% and 80–87%, respectively, through biological processes that were achieved using either a sequencing batch reactor (SBR, site A) or an anaerobic–aerobic biodigester (EcoSan, site B). Complete disinfection of E. coli with nil CFU per ml was achieved using electrochemical processes that also served to remove the remaining organic and nutrient loading to over 90–96%. The treated water was reused for flushing by the residents of the apartment building for 89 days

EcoBlock: Grid Impacts, Scaling, and Resilience

Widespread deployment of EcoBlocks has the potential to transform today's electricity system into one that is more resilient, flexible, efficient and sustainable. In this vision, the system will consist of self- su cient, renewable-powered, block-scale entities that can deliberately adjust their net power exchange and can optimize performance, maintain stability, support each other, or disconnect entirely from the grid as needed. This report is intended as an independent analysis of the potential relationships, both constructive and adverse, between EcoBlocks and the grid