The influence of alcohol (0.5‰) on the control and manoeuvring level of driving behaviour, finding measures to assess driving impairment:A simulator study

Objective: The influence of psychoactive substances on driving performance and traffic safety has been extensively studied. Research on the influence of alcohol at the control level of behaviour (i.e. automated processes) has been well established and has shown that the ability to operate a vehicle decreases with rising alcohol levels. However, results one level higher at the manoeuvring level (i.e. conscious processes), are inconsistent. The current study aimed to replicate findings on the influence of alcohol on the control level of behaviour and investigate effects on the manoeuvring level in order to find suitable measures to assess driving impairment. Method: The study was double-blind, placebo-controlled with a counterbalanced treatment order and a two-way crossover design. Thirty participants performed tasks in a driving simulator under the influence of alcohol (0.5‰) and a placebo. In the driving tasks the control level of behaviour (swerving, average speed, and speed variation) was investigated, as well as the manoeuvring level of behaviour (distance to other traffic during an overtaking manoeuvre, reaction time to a traffic light turning amber, and response to a suddenly merging car). Results: As expected, alcohol affected the control level of behaviour negatively. Participants swerved more and showed more speed variation after alcohol intake. The manoeuvring level of driving behaviour was also affected by alcohol. The distance to other drivers during an overtaking manoeuvre was smaller under the influence of alcohol. Results on reaction time were however less straightforward. Reaction time increased significantly under the influence of alcohol when reacting to a traffic light but not in reaction to a car unexpectedly merging into traffic. When analysing behaviour in reaction to these different events in more detail it became clear that they were responded to in varying manners, making it difficult to find an average impairment measure. Conclusions: The deteriorating effect of alcohol at the control level of driving behaviour was replicated, confirming the suitability of the standard deviation of lateral position and the variation in speed as measures of impairment. At the manoeuvring level, the kept distance to the leading car during an overtaking manoeuvre appeared to be a suitable measure to assess impairment as well as reaction time to a traffic light. The current study also confirms the difficulties in evaluating complex driving behaviour and the need for more research on this subject

Driving performance and neurocognitive skills of long-term users of sedating antidepressants

Objective: To assess driving performance and neurocognitive skills of long‐term users of sedating antidepressants, in comparison to healthy controls. Methods: Thirty‐eight long‐term (>6 months) users of amitriptyline (n = 13) and mirtazapine (n = 25) were compared to 65 healthy controls. Driving performance was assessed using a 1‐h standardised highway driving test in actual traffic, with road‐tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance. Results: Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: - 0.83 cm; +2.33 cm). However, users treated less than 3 years (n = 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non‐inferiority for users treated longer than 3 years. Conclusion: The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long‐term use of 3 years

An explorative approach to understanding individual differences in driving performance and neurocognition in long-term benzodiazepine users

Objective: Previous research reported cognitive and psychomotor impairments in long‐term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints. Methods: Neurocognitive and on‐road driving performance of 19 long‐term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self‐reported use, exceeding the therapeutic threshold (CBZRA+), and 31 long‐term regular BZRA users below (CBZRA−), was compared to that of 76 controls. Results: BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self‐reported clinical complaints, was a significant covariate. Road‐tracking performance was explained by CBZRA only. The CBZRA + group exhibited increased mean standard deviation of lateral position comparable to that at blood‐alcohol concentrations of 0.5 g/L. Conclusions: Functional impairments in long‐term BZRA users are not attributable to self‐reported clinical complaints or estimated BZRA concentrations, except for road‐tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long‐term BZRA users

Defining binding efficiency and specificity of auxins for SCF(TIR1/AFB)-Aux/IAA co-receptor complex formation.

Structure-activity profiles for the phytohormone auxin have been collected for over 70 years, and a number of synthetic auxins are used in agriculture. Auxin classification schemes and binding models followed from understanding auxin structures. However, all of the data came from whole plant bioassays, meaning the output was the integral of many different processes. The discovery of Transport Inhibitor-Response 1 (TIR1) and the Auxin F-Box (AFB) proteins as sites of auxin perception and the role of auxin as molecular glue in the assembly of co-receptor complexes has allowed the development of a definitive quantitative structure-activity relationship for TIR1 and AFB5. Factorial analysis of binding activities offered two uncorrelated factors associated with binding efficiency and binding selectivity. The six maximum-likelihood estimators of Efficiency are changes in the overlap matrixes, inferring that Efficiency is related to the volume of the electronic system. Using the subset of compounds that bound strongly, chemometric analyses based on quantum chemical calculations and similarity and self-similarity indices yielded three classes of Specificity that relate to differential binding. Specificity may not be defined by any one specific atom or position and is influenced by coulomb matrixes, suggesting that it is driven by electrostatic forces. These analyses give the first receptor-specific classification of auxins and indicate that AFB5 is the preferred site for a number of auxinic herbicides by allowing interactions with analogues having van der Waals surfaces larger than that of indole-3-acetic acid. The quality factors are also examined in terms of long-standing models for the mechanism of auxin binding