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A Hogewoning,1,* AJAE Van de Loo,1,* M Mackus,1 SJ Raasveld,1 R De Zeeuw,1 ER Bosma,1 NH Bouwmeester,1 KA Brookhuis,2 J Garssen,1,3 JC Verster1,4 1Division of Pharmacology, Utrecht University, Utrecht, 2Faculty of Behavioral and Social Sciences, Groningen University, Groningen, 3Nutricia Research, Utrecht, the Netherlands; 4Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia *These authors contributed equally to this work Background: A number of social drinkers claim that they do not experience next-day hangovers despite consuming large quantities of alcohol. The aim of this study was to investigate the characteristics of drinkers who claim to be hangover immune and compare them with drinkers who do report having hangovers. Methods: A total of 36 social drinkers participated in a naturalistic study consisting of a hangover day (alcohol consumed) and a control day (no alcohol consumed). Data were collected on alcohol consumption, demographics, sleep, next-day adverse effects, and mood. Data from drinkers with a hangover (N=18) were compared with data from drinkers who claim to be hangover immune (N=18). Results: Drinkers with a hangover reported drowsiness-related symptoms, symptoms related to reduced cognitive functioning, and classic hangover symptoms such as headache, nausea, dizziness, weakness, and stomach pain. Corresponding mood changes comprised increased feelings of depression, anger–hostility, fatigue, and reduced vigor–activity. In contrast, hangover-immune drinkers reported relatively few hangover symptoms, with only mild corresponding severity scores. The reported symptoms were limited to drowsiness-related symptoms such as sleepiness and being tired. The classic hangover symptoms were usually not reported by these drinkers. Conclusion: In contrast to drinkers with a hangover, for those who claim to be hangover immune, next-day adverse effects of alcohol consumption are limited to a mild increase in drowsiness-related symptoms. Keywords: alcohol, hangover, symptoms, mood, immunity

Land transactions between farmers are responsible for landscape changes in rural areas. The price a farmer is willing to pay (WTP) for vacant land depends on the distance of the parcel to the farmstead. Detailed quantitative knowledge of this WTP– distance relationship is of utmost importance for accurate modelling of land markets, and for the design and implementation of effective and robust land consolidation schemes. Practical experience suggests, however that it is not particularly easy to back out the WTP–distance relationship from empirical transaction data. Here, we present a novel statistical framework to help quantify the relationship between a farmer's WTP and the distance of his/her farmstead to the vacant parcel. We describe a land market with a simple statistical model and simulate an artificial archive of land transactions via Monte Carlo sampling. The parameters of our virtual market are estimated from a historical archive of land transactions in the Province of Gelderland The Netherlands, using minimization of the divergence (relative entropy) between the observed and simulated joint distributions of distance and transaction price. A reasonable agreement was observed between the observed and simulated bivariate distributions of distance and transaction price. Our results demonstrate that for short distances (500–1000m) any additional metre distance reduces the WTP by about 60 € ha-1. The impact of distance on WTP gradually levels off with larger distance: beyond 5 km the effect has reduced to less than 0.5 € ha-1

Objective: Using benzodiazepines and certain antidepressants is associated with an increased risk of motor vehicle crashes due to impaired driving skills. Hence, several countries prohibit people who use these drugs from driving. Traffic regulations for driving under the influence of these drugs are, however, largely based on single-dose studies with healthy participants. The effects of drugs on chronic users may be different because of potential development of tolerance or by adapting behavior. In this study, we test the effects of anti-depressants, hypnotics, or anxiolytics use on driving performance in patients who use these drugs for different durations and compare the effects to healthy controls' performance. Methods: Sixty-six healthy controls and 82 medication users were recruited to perform four drives in a driving simulator. Patients were divided into groups that used anti-depressants, hypnotics, or anxiolytics, for shorter or longer than 3 years (i.e. LT3− or LT3+, respectively). The minimum term of use was 6 months. Driving behavior was measured in terms of longitudinal and lateral control (speed variability and Standard Deviation of Lateral Position: SDLP), brake reaction time, and time headway. Impaired driving performance was defined as performing similar to driving with a Blood Alcohol Concentration of 0.5‰ or higher, determined by means of non-inferiority analyses. Results: Reaction time analyses revealed inconclusive findings in all groups. No significant performance differences between matched healthy controls, LT3− (n = 2), and LT3+ (n = 8) anxiolytics users were found. LT3+ antidepressants users (n = 12) did not perform inferior to their matched controls in terms of SDLP. LT3− hypnotics users (n = 6) showed more speed variability than their matched healthy controls, while this effect was not found for the LT3+ group (n = 14): the latter did not perform inferior to the healthy controls. Regarding Time Headway, no conclusions about the LT3− hypnotics group could be drawn, while the LT3+ group did not perform inferior compared to the control group. Conclusions: The small number of anxiolytics users prohibits drawing conclusions about clinical relevance. Although many outcomes were inconclusive, there is evidence that some elements of complex driving performance may not be impaired (anymore) after using antidepressants or hypnotics longer than 3 years. [ABSTRACT FROM AUTHOR]

This review describes acetaminophen pharmacokinetics (PK) throughout pregnancy, as analyzed by three methods (non-compartmental analyses (NCA), population PK, and physiologically based PK (PBPK) modelling). Eighteen studies using NCA were reported in the scientific literature. These studies reported an increase in the volume of distribution (3.5–60.7%) and an increase in the clearance (36.8–84.4%) of acetaminophen in pregnant women compared to non-pregnant women. Only two studies using population PK modelling as a technique were available in the literature. The largest difference in acetaminophen clearance (203%) was observed in women at delivery compared to non-pregnant women. One study using the PBPK technique was found in the literature. This study focused on the formation of metabolites, and the toxic metabolite N-acetyl-p-benzoquinone imine was the highest in the first trimester, followed by the second and third trimester, compared with non-pregnant women. In conclusion, this review gave an overview on acetaminophen PK changes in pregnancy. Also, knowledge gaps, such as fetal and placenta PK parameters, have been identified, which should be explored further before dosing adjustments can be suggested on an evidence-based basis.

Pedestrians are commonly engaged in other activities while walking. The current study assesses (1) whether pedestrians are sufficiently aware of their surroundings to successfully negotiate obstacles in a city, and (2) whether various common walking practices affect awareness of obstacles and, or, avoidance behavior. To this end, an obstacle, i.e., a signboard was placed on a pavement in the city centre of Utrecht, the Netherlands. The behavioral measure consisted of the distance to the signboard before pedestrians moved to avoid it. After passing, participants were interviewed to obtain thought samples, self-reported route familiarity, a confirmation of secondary task engagement, and to assess awareness through recall and recognition of the signboard and its text. In this study 234 pedestrians participated. More than half of the participants (53.8%) was unaware of the signboard, still none of them had bumped into it. Mind wandering, being engaged in secondary tasks such as talking with a companion or using a mobile phone, and being familiar with a route, did not affect awareness nor avoidance behavior. In conclusion, despite being very common there was no evidence that walking without awareness necessarily results in risk. The absence of awareness does not imply any absence of cognitive and perceptual processing. Pedestrians are still capable of successfully avoiding obstacles in their path, even in visually more challenging environments such as a city centre. It is argued that this is because walking consists of highly automated, skilled behavior.

Distracted driving is considered to be an important factor in road safety. To investigate how experienced user's driving behaviour is affected by in-vehicle technology, a fixed-base driving simulator was used. 20 participants drove twice in a rich simulated traffic environment while performing secondary, i.e. mobile phone and navigation system tasks. The results show that mean speed was lower in all experimental conditions, compared to baseline driving, while subjective effort increased. Lateral performance deteriorated only during visual–manual tasks, i.e. texting and destination entry, in which the participants glanced off the forward road for a substantial amount of time. Being experienced in manipulating in-car devices does not solve the problem of dual tasking when the primary task is a complex task like driving a moving vehicle. The results and discussion may shed some light on the current debate regarding phone use hazards.