Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

A neuroimaging approach to evaluate choices and compare performance of tower air traffic controllers during missed approaches

The aim of this research is to use functional Near-Infrared Spectroscopy to compare and contrast brain activation for professional versus novice Tower Air Traffic Controllers when performing their daily tasks, whilst accounting for missed approaches. With functional Near-Infrared Spectroscopy chosen due to its ability to continuously monitor brain activity for mobile participants in their workplace settings, increasing eco-logical validity, as well as being safe, inexpensive, and benefitting from low set-up times, resulting in excellent temporal resolution as well as superior spatial resolution over Electroencephalogram. If a significant difference in activation is observed between professional and novice ATCOs, the neuroimaging data can be used as a benchmark for future exploratory studies using the obtained neuroimaging data to serve as a reliable quantitative measure to track performance during Air Traffic Controller training, establishing a metric to distinguish novice from professional Air Traffic Controllers. Our hypothesis is that professional tower controllers will have a decrease in brain activation due to their experience. Contrastingly, novice tower controllers would have more extensive brain activation, given a lack of experience relying soley on training. Additionally, we expect to see a significant difference in sustained attention activation between professionals and novices. The tasks that the tower controllers will be expected to resolve will be a series of tower control duties that will be severely impacted by a range of factors that will intentionally make the successful performance of their duties strained.Civil Aviation Authority of Singapore (CAAS)Accepted versionThis work was made possible through the NTU-CAAS Research Grant M4062429.056.706022 by Air Traffic Management Research Insitute, and the school of mechancial engineering NTU. Ethics approval for this research was granted by the Nanyang Technological University (NTU) institional review board (IRB) (IRB-2020-01-026). A special thank you goes out to Lab Manager Kevin of the ATMRI whose assistance with the tower simulator made the whole project possible

A review on electric vehicles and their interaction with smart grids: the case of Brazil

This work provides a comprehensive literature review to evaluate the expected impacts of the introduction of electric vehicles into the power electric system with smart grid, examining the case of Brazil. Previous studies point out to different impact levels with the introduction of electric vehicles in the country’s electric grid, varying from small impacts for substitution of 10 % of the fleet, to potential difficulties if more than 20 % of the fleet is replaced. Electric vehicles offer significant advantages over their internal combustion engine powered vehicles counterparts, including the higher efficiency and performance of the electric motor, reduced pollution emissions during operation, and decreased noise levels. The current disadvantages lie mainly with the higher vehicle and battery costs, relatively long battery-charging period required, limited battery lifetime, and the need to increase market availability. Brazil’s electricity generation capacity is primarily based on clean and renewable energy (hydropower, wind, biomass), providing the preferred approach to charge electric vehicles with minimal carbon and other pollutant emissions. With the introduction of smart grids in the country’s electricity distribution structure, electric vehicles also provide a pathway (with renewable energy options) toward cleaner electricity, leveling the power demand cycle, and lowering the need to add costly central station generation by integrating them into the grid itself during periods when they are not used for transportation. However, careful studies must be conducted mainly due to the need to increase electric power generation to meet existing and imminent demands

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

International audienceAcute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroid-refractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

Liver fibrosis is a common pathway leading to cirrhosis, which is the final result of injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Liver biopsy has been considered to be the “gold standard” to assess fibrosis. However, liver biopsy being invasive and, in many instances, not favored by patients or physicians, alternative approaches to assess liver fibrosis have assumed great importance. Moreover, therapies aimed at reversing the liver fibrosis have also been tried lately with variable results. Till now, there has been no consensus on various clinical, pathological, and radiological aspects of liver fibrosis. The Asian Pacific Association for the Study of the Liver set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The process for the development of these consensus guidelines involved the following: review of all available published literature by a core group of experts; proposal of consensus statements by the experts; discussion of the contentious issues; and unanimous approval of the consensus statements after discussion. The Oxford System of evidence-based approach was adopted for developing the consensus statements using the level of evidence from 1 (highest) to 5 (lowest) and grade of recommendation from A (strongest) to D (weakest). The consensus statements are presented in this review