A European project is gradually replacing the current train control systems to a mutual control system called as the European Railway Traffic Management System (ERTMS). I Sweden they have implemented the new train control system on a few train-lines in the northern part of Sweden. There has been reported problems from train drivers that have used the new control system, the problems consist of both negative affects on train performance and railroad capacity. This study is part of a larger project conducted by The Swedish National Road and Transport Research Institute, with an aim to investigate how the attention is affected in the new train control system compared to the Automatic Train Control (ATC) system. Data collection through eye-tracking have shown significant results in the distribution of visual glances inside and outside the cabin of the train. Drivers tend to distribute more and longer glances inside the train with the ERTMS. Drivers also tend to miss information presented on the track, such as signs informing when to make a sound before an unattended level crossing. These results suggest that ERTMS could have a negative impact on the drivers situation awareness and also could have a negative affect on the drivers attention that impacts the ability to notice what is happening outside the cabin. / I dagsläget utförs ett projekt i Europa med syfte att ersätta nuvarande tågskyddssystem till ett gemensamt signalsystem kallat ERTMS (European Railway Traffic Management System). Detta nya system har implementerats på ett fåtal tåg-linjer i norra delen av Sverige. Olika problem har rapporterats från tågförare som använt det nya signalsystemet. Dessa problem innefattar negativ påverkan på prestation och järnvägens kapacitet. Denna studie är en del av ett större projekt hos Statens väg- och transportforskningsinstitut med ett syfte att studera hur uppmärksamhet påverkas i det nya tågskyddssystemet ERTMS jämfört med det nuvarande systemet ATC (Automatic Train Control). Data som samlades in via eye-tracking har visat signifikanta resultat i fördelning av visuella blickar inne i och utanför tågets kabin. Förare tenderar att fördela mer och även längre blickar inuti tågets kabin med ERTMS. Dessutom tenderar förare att missa information som presenteras ute på spåret, detta kan exempelvis vara information som påvisar att tuta innan ett obevakat övergångsställe. Dessa resultat föreslår att ERTMS kan ha en negativ påverkan på förares uppmärksamhet vilket kan påverka förarens förmåga att bli varse om vad som händer utanför kabinen, på spåret.

Indiana University-Purdue University Indianapolis (IUPUI) / Drug-drug interactions (DDIs) refer to situations where one drug affects the pharmacokinetics or pharmacodynamics of another. DDIs represent a major cause of morbidity and mortality. A common adverse drug reaction (ADR) that can result from, or be exacerbated by DDIs is drug-induced myopathy. Identifying DDIs and understanding their underlying mechanisms is key to the prevention of undesirable effects of DDIs and to efforts to optimize therapeutic outcomes. This dissertation is dedicated to identification of clinically important myopathic DDIs and to elucidation of their underlying mechanisms. Using data mined from the published cytochrome P450 (CYP) drug interaction literature, 13,197 drug pairs were predicted to potentially interact by pairing a substrate and an inhibitor of a major CYP isoform in humans. Prescribing data for these drug pairs and their associations with myopathy were then examined in a large electronic medical record database. The analyses identified fifteen drug pairs as DDIs significantly associated with an increased risk of myopathy. These significant myopathic DDIs involved clinically important drugs including alprazolam, chloroquine, duloxetine, hydroxychloroquine, loratadine, omeprazole, promethazine, quetiapine, risperidone, ropinirole, trazodone and simvastatin. Data from in vitro experiments indicated that the interaction between quetiapine and chloroquine (risk ratio, RR, 2.17, p-value 5.29E-05) may result from the inhibitory effects of quetiapine on chloroquine metabolism by cytochrome P450s (CYPs). The in vitro data also suggested that the interaction between simvastatin and loratadine (RR 1.6, p-value 4.75E-07) may result from synergistic toxicity of simvastatin and desloratadine, the major metabolite of loratadine, to muscle cells, and from the inhibitory effect of simvastatin acid, the active metabolite of simvastatin, on the hepatic uptake of desloratadine via OATP1B1/1B3. Our data not only identified unknown myopathic DDIs of clinical consequence, but also shed light on their underlying pharmacokinetic and pharmacodynamic mechanisms. More importantly, our approach exemplified a new strategy for identification and investigation of DDIs, one that combined literature mining using bioinformatic algorithms, ADR detection using a pharmacoepidemiologic design, and mechanistic studies employing in vitro experimental models.