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Better disease management can be achieved with earlier detection through robust, sensitive, and easily accessible biomarkers. The aim of the current study was to identify novel epigenetic biomarkers determining the risk of type 2 diabetes (T2D). Livers of 10-week-old female New Zealand Obese (NZO) mice, slightly differing in their degree of hyperglycemia and liver fat content and thereby in their diabetes susceptibility were used for expression and methylation profiling. We screened for differences in hepatic expression and DNA methylation in diabetes-prone and -resistant mice, and verified a candidate (HAMP) in human livers and blood cells. Hamp expression was manipulated in primary hepatocytes and insulin-stimulated pAKT was detected. Luciferase reporter assays were conducted in a murine liver cell line to test the impact of DNA methylation on promoter activity. In livers of NZO mice, the overlap of methylome and transcriptome analyses revealed a potential transcriptional dysregulation of 12 hepatokines. The strongest effect with a 52% decreased expression in livers of diabetes-prone mice was detected for the Hamp gene, mediated by elevated DNA methylation of two CpG sites located in the promoter. Hamp encodes the iron-regulatory hormone hepcidin, which had a lower abundance in the livers of mice prone to developing diabetes. Suppression of Hamp reduces the levels of pAKT in insulin-treated hepatocytes. In liver biopsies of obese insulin-resistant women, HAMP expression was significantly downregulated along with increased DNA methylation of a homologous CpG site. In blood cells of incident T2D cases from the prospective EPIC-Potsdam cohort, higher DNA methylation of two CpG sites was related to increased risk of incident diabetes. We identified epigenetic changes in the HAMP gene which may be used as an early marker preceding T2D. • Hamp expression in livers of diabetes-prone mice is epigenetically regulated. • Livers of obese insulin-resistant women exhibit a reduced HAMP expression. • In the liver of insulin-resistant women, the HAMP promoter is hypermethylated. • In blood cells, hypermethylation of HAMP associates with an increased T2D risk. • Hypermethylation of the Hamp / HAMP promoter preceded the onset of T2D. [ABSTRACT FROM AUTHOR]

• 46% of car passengers report some level of carsickness in the past five years. • Including childhood experiences, this rate increases to 59%. • The highest incidence was reported in China, the lowest in Germany. • Incidence differs consistently by age and gender (female > male; young > old). • Main modulating factors are driving dynamics, visual activities, low air quality. About two in three people have experienced carsickness at some point in their life (Reason & Brand, 1975). Little is known about current numbers of sufferers, cultural differences, or which modulating factors are being perceived as most relevant. Therefore, given a global increase of interest in carsickness driven by the development of automated vehicles, this survey intended to assess the status quo of carsickness in different parts of the world. We conducted an online survey with N = 4,479 participants in Brazil, China, Germany, UK and USA. 46% of participants indicated they had experienced some degree of carsickness in the past five years as a passenger in a car. When including childhood experiences, this rate increased to 59%, comparable to the 1975 findings by Reason and Brand. The highest and lowest incidence of carsickness was reported in China and Germany, respectively. In all countries, men and older participants reported a lower incidence of carsickness as compared to females and younger participants. The main modulating factors were found to be driving dynamics, visual activities, and low air quality. This study showed that carsickness still affects about 2/3 of passengers and discusses how its occurrence relates to in-transit activities and other modes of transport. The research provides a sound basis to further study how carsickness develops and to investigate countermeasures to potentially reduce it. [ABSTRACT FROM AUTHOR]

• Increasingly dropouts from universities re-enroll at another tertiary institution. • We study the effect of these dropouts on the academic success of their new peers. • Dropouts re-enrolling in the same field have a negative impact on their new peers. • While those re-enrolling in a different field have a positive effect. • Effects vary nonlinearly with different treatment intensities and levels. We investigate the impact of the presence of university dropouts on the academic success of first-time students in universities of applied sciences. Our identification strategy relies on quasi-random variation in the proportion of dropouts. The estimated average zero effect of dropouts on first-time students' success masks treatment heterogeneity and non-linearities. First, we find negative effects on the academic success of their new peers from dropouts who had re-enrolled in the same subject and, conversely, positive effects of dropouts changing subjects. Second, we use causal machine learning methods to find that the effects vary nonlinearly with different treatment intensities and prevailing treatment levels. [ABSTRACT FROM AUTHOR]

Abstract: We use a unique data set about the wage distribution that Swiss students expect for themselves ex ante, deriving parametric and non-parametric measures to capture expected wage risk. These wage risk measures are unfettered by heterogeneity which handicapped the use of actual market wage dispersion as risk measure in earlier studies. Students in our sample anticipate that the market provides compensation for risk, as has been established with risk augmented Mincer earnings equations estimated on market data: higher wage risk for educational groups is associated with higher mean wages. With observations on risk as expected by students we find compensation at similar elasticities as observed in market data. The results are robust to different specifications and estimation models. [Copyright &y& Elsevier]

This study investigated driver performance during system limits of partially automated driving. Using a motion-based driving simulator, drivers encountered different situations in which a partially automated vehicle could no longer safely keep the lateral guidance. Drivers were distracted by a non-driving related task on a touch display or driving without an additional secondary task. While driving in partially automated mode drivers could either take their hands off the steering wheel for only a short period of time (10 s, so-called ‘Hands-on’ variant) or for an extended period of time (120 s, so-called ‘Hands-off’ variant). When the system limit was reached (e.g., when entering a work zone with temporary lines), the lateral vehicle control by the automation was suddenly discontinued and a take-over request was issued to the drivers. Regardless of the hands-off interval and the availability of a secondary task, all drivers managed the transition to manual driving safely. No lane exceedances were observed and the situations were rated as ‘harmless’ by the drivers. The lack of difference between the hands-off intervals can be partly attributed to the fact that most of the drivers kept contact to the steering wheel, even in the hands-off condition. Although all drivers were able to control the system limits, most of them could not explain why exactly the take-over request was issued. The average helpfulness of the take-over request was rated on an intermediate level. Consequently, providing drivers with information about the reason for a system limit can be recommended. [ABSTRACT FROM AUTHOR]

Different motor vehicle manufacturers have recently introduced assistance systems that are capable of both longitudinal and lateral vehicle control, while the driver still has to be able to take over the vehicle control at all times (so-called Partial Automation ). While these systems usually allow hands-free driving only for short time periods (e.g., 10 s), there has been little research whether allowing longer time periods of hands-off driving actually has a negative impact on driving safety in situations that the automation cannot handle alone. Altogether, two partially automated assistance systems, differing in the permitted hands-off intervals (Hands-off system vs. Hands-on system, n = 20 participants per assistance condition, age 25–70 years) were implemented in the driving simulation with a realistic take-over concept. The Hands-off system is defined by having a permitted hands-off interval of 120 s, while the Hands-on system is defined by a permitted hands-off interval of 10 s. Drivers’ reactions at a functional system limit were tested under conditions of high ecological validity: while driving in a traffic jam, participants unexpectedly encountered a time-critical situation, consisting of a vehicle at standstill that appeared suddenly and required immediate action. A visual-auditory take-over request was issued to the drivers. Regardless of the hands-off interval, all participants brought the vehicle to a safe stop. In spite of a stronger brake reaction with the Hands-on system, no significant differences between assistance levels were found in brake reaction times and the criticality of the situation. The reason for this may be that most of the drivers kept contact with the steering wheel, even in the Hands-off condition. Neither age nor prior experience with ACC was found to impact the results. The study thus demonstrates that permitting longer periods of hands-off driving does not necessarily lead to performance deficits of the driver in the case of take-over situations, if a comprehensive take-over concept is implemented. [ABSTRACT FROM AUTHOR]