Can a novel web-based computer test predict poor simulated driving performance? A pilot study with healthy and cognitive-impaired participants

BACKGROUND Driving a car is a complex instrumental activity of daily living and driving performance is very sensitive to cognitive impairment. The assessment of driving-relevant cognition in older drivers is challenging and requires reliable and valid tests with good sensitivity and specificity to predict safe driving. Driving simulators can be used to test fitness to drive. Several studies have found strong correlation between driving simulator performance and on-the-road driving. However, access to driving simulators is restricted to specialists and simulators are too expensive, large, and complex to allow easy access to older drivers or physicians advising them. An easily accessible, Web-based, cognitive screening test could offer a solution to this problem. The World Wide Web allows easy dissemination of the test software and implementation of the scoring algorithm on a central server, allowing generation of a dynamically growing database with normative values and ensures that all users have access to the same up-to-date normative values. OBJECTIVE In this pilot study, we present the novel Web-based Bern Cognitive Screening Test (wBCST) and investigate whether it can predict poor simulated driving performance in healthy and cognitive-impaired participants. METHODS The wBCST performance and simulated driving performance have been analyzed in 26 healthy younger and 44 healthy older participants as well as in 10 older participants with cognitive impairment. Correlations between the two tests were calculated. Also, simulated driving performance was used to group the participants into good performers (n=70) and poor performers (n=10). A receiver-operating characteristic analysis was calculated to determine sensitivity and specificity of the wBCST in predicting simulated driving performance. RESULTS The mean wBCST score of the participants with poor simulated driving performance was reduced by 52%, compared to participants with good simulated driving performance (P<.001). The area under the receiver-operating characteristic curve was 0.80 with a 95% confidence interval 0.68-0.92. CONCLUSIONS When selecting a 75% test score as the cutoff, the novel test has 83% sensitivity, 70% specificity, and 81% efficiency, which are good values for a screening test. Overall, in this pilot study, the novel Web-based computer test appears to be a promising tool for supporting clinicians in fitness-to-drive assessments of older drivers. The Web-based distribution and scoring on a central computer will facilitate further evaluation of the novel test setup. We expect that in the near future, Web-based computer tests will become a valid and reliable tool for clinicians, for example, when assessing fitness to drive in older drivers.

Learning to drive: learners' self-reported cognitive failure level predicts driving instructor's observation rating of driving performance

OBJECTIVES Evidence increases that cognitive failure may be used to screen for drivers at risk. Until now, most studies have relied on driving learners. This exploratory pilot study examines self-report of cognitive failure in driving beginners and error during real driving as observed by driving instructors. METHODS Forty-two driving learners of 14 driving instructors filled out a work-related cognitive failure questionnaire. Driving instructors observed driving errors during the next driving lesson. In multiple linear regression analysis, driving errors were regressed on cognitive failure with the number of driving lessons as an estimator of driving experience controlled. RESULTS Higher cognitive failure predicted more driving errors (p < .01) when age, gender and driving experience were controlled in analysis. CONCLUSIONS Cognitive failure was significantly associated with observed driving errors. Systematic research on cognitive failure in driving beginners is recommended.

Variation in fat mobilization during early lactation differently affects feed intake, body condition, and lipid and glucose metabolism in high-yielding dairy cows.

Fat mobilization to meet energy requirements during early lactation is inevitable because of insufficient feed intake, but differs greatly among high-yielding dairy cows. Therefore, we studied milk production, feed intake, and body condition as well as metabolic and endocrine changes in high-yielding dairy cows to identify variable strategies in metabolic and endocrine adaptation to overcome postpartum metabolic load attributable to milk production. Cows used in this study varied in fat mobilization around calving, as classified by mean total liver fat concentrations (LFC) postpartum. German Holstein cows (n=27) were studied from dry off until d 63 postpartum in their third lactation. All cows were fed the same total mixed rations ad libitum during the dry period and lactation. Plasma concentrations of metabolites and hormones were measured in blood samples taken at d 56, 28, 15, and 5 before expected calving and at d 1 and once weekly up to d 63 postpartum. Liver biopsies were taken on d 56 and 15 before calving, and on d 1, 14, 28, and 49 postpartum to measure LFC and glycogen concentrations. Cows were grouped accordingly to mean total LFC on d 1, 14, and 28 in high, medium, and low fat-mobilizing cows. Mean LFC (±SEM) differed among groups and were 351±14, 250±10, and 159±9 mg/g of dry matter for high, medium, and low fat-mobilizing cows, respectively, whereas hepatic glycogen concentrations postpartum were the highest in low fat-mobilizing cows. Cows in the low group showed the highest dry matter intake and the least negative energy balance postpartum, but energy-corrected milk yield was similar among groups. The decrease in body weight postpartum was greatest in high fat-mobilizing cows, but the decrease in backfat thickness was greatest in medium fat-mobilizing cows. Plasma concentrations of nonesterified fatty acids and β-hydroxybutyrate were highest around calving in high fat-mobilizing cows. Plasma triglycerides were highest in the medium group and plasma cholesterol concentrations were lowest in the high group at calving. During early lactation, the decrease in plasma glucose concentrations was greatest in the high group, and plasma insulin concentrations postpartum were highest in the low group. The revised quantitative insulin sensitivity check index values decreased during the transition period and postpartum, and were highest in the medium group. Plasma cortisol concentrations during the transition period and postpartum period and plasma leptin concentrations were highest in the medium group. In conclusion, cows adapted differently to the metabolic load and used variable strategies for homeorhetic regulation of milk production. Differences in fat mobilization were part of these strategies and contributed to the individual adaptation of energy metabolism to milk production.

Antibodies trap tissue migrating helminth larvae and prevent tissue damage by driving IL-4Rα-independent alternative differentiation of macrophages

Approximately one-third of the world's population suffers from chronic helminth infections with no effective vaccines currently available. Antibodies and alternatively activated macrophages (AAM) form crucial components of protective immunity against challenge infections with intestinal helminths. However, the mechanisms by which antibodies target these large multi-cellular parasites remain obscure. Alternative activation of macrophages during helminth infection has been linked to signaling through the IL-4 receptor alpha chain (IL-4Rα), but the potential effects of antibodies on macrophage differentiation have not been explored. We demonstrate that helminth-specific antibodies induce the rapid trapping of tissue migrating helminth larvae and prevent tissue necrosis following challenge infection with the natural murine parasite Heligmosomoides polygyrus bakeri (Hp). Mice lacking antibodies (JH (-/-)) or activating Fc receptors (FcRγ(-/-)) harbored highly motile larvae, developed extensive tissue damage and accumulated less Arginase-1 expressing macrophages around the larvae. Moreover, Hp-specific antibodies induced FcRγ- and complement-dependent adherence of macrophages to larvae in vitro, resulting in complete larval immobilization. Antibodies together with helminth larvae reprogrammed macrophages to express wound-healing associated genes, including Arginase-1, and the Arginase-1 product L-ornithine directly impaired larval motility. Antibody-induced expression of Arginase-1 in vitro and in vivo occurred independently of IL-4Rα signaling. In summary, we present a novel IL-4Rα-independent mechanism of alternative macrophage activation that is antibody-dependent and which both mediates anti-helminth immunity and prevents tissue disruption caused by migrating larvae.

Deciphering the driving forces of erosion rates on millennial to million-year timescales in glacially impacted landscapes: An example from the Western Alps

In many regions, tectonic uplift is the main driver of erosion over million-year (Myr) timescales, but climate changes can markedly affect the link between tectonics and erosion, causing transient variations in erosion rates. Here we study the driving forces of millennial to Myr-scale erosion rates in the French Western Alps, as estimated from in situ produced cosmogenic 10Be and a newly developed approach integrating detrital and bedrock apatite fission-track thermochronology. Millennial erosion rates from 10Be analyses vary between ~0.27 and ~1.33 m/kyr, similar to rates measured in adjacent areas of the Alps. Significant positive correlations of millennial erosion rates with geomorphic measures, in particular with the LGM ice thickness, reveal a strong transient morphological and erosional perturbation caused by repeated Quaternary glaciations. The perturbation appears independent of Myr-scale uplift and erosion gradients, with the effect that millennial erosion rates exceed Myr-scale erosion rates only in the internal Alps where the latter are low (<0.4 km/Myr). These areas, moreover, exhibit channels that clearly plot above a general linear positive relation between Myr-scale erosion rates and normalized steepness index. Glacial erosion acts irrespective of rock uplift and thus not only leads to an overall increase in erosion rates but also regulates landscape morphology and erosion rates in regions with considerable spatial gradients in Myr-scale tectonic uplift. Our study demonstrates that climate change, e.g., through occurrence of major glaciations, can markedly perturb landscape morphology and related millennial erosion rate patterns, even in regions where Myr-scale erosion rates are dominantly controlled by tectonics.

A novel computer test to assess driving-relevant cognitive functions - a pilot study

BACKGROUND: The assessment of driving-relevant cognitive functions in older drivers is a difficult challenge as there is no clear-cut dividing line between normal cognition and impaired cognition and not all cognitive functions are equally important for driving. METHODS: To support decision makers, the Bern Cognitive Screening Test (BCST) for older drivers was designed. It is a computer-assisted test battery assessing visuo-spatial attention, executive functions, eye-hand coordination, distance judgment, and speed regulation. Here we compare the performance in BCST with the performance in paper and pencil cognitive screening tests and the performance in the driving simulator testing of 41 safe drivers (without crash history) and 14 unsafe drivers (with crash history). RESULTS: Safe drivers performed better than unsafe drivers in BCST (Mann-Whitney U test: U = 125.5; p = 0.001) and in the driving simulator (Student's t-test: t(44) = -2.64, p = 0.006). No clear group differences were found in paper and pencil screening tests (p > 0.05; ns). BCST was best at identifying older unsafe drivers (sensitivity 86%; specificity 61%) and was also better tolerated than the driving simulator test with fewer dropouts. CONCLUSIONS: BCST is more accurate than paper and pencil screening tests, and better tolerated than driving simulator testing when assessing driving-relevant cognition in older drivers.

Size-Fractionated Nitrogen Uptake Measurements in the Equatorial Pacific and Confirmation of the Low Si-High-Nitrate Low-Chlorophyll Condition

The equatorial Pacific Ocean is the largest natural source of CO(2) to the atmosphere, and it significantly impacts the global carbon cycle. Much of the large flux of upwelled CO(2) to the atmosphere is due to incomplete use of the available nitrate (NO(3)) and low net productivity. This high-nutrient low-chlorophyll (HNLC) condition of the equatorial upwelling zone (EUZ) has been interpreted from modeling efforts to be due to low levels of silicate ( Si( OH) 4) that limit the new production of diatoms. These ideas were incorporated into an ecosystem model, CoSINE. This model predicted production by the larger phytoplankton and the picoplankton and effects on air-sea CO(2) fluxes in the Pacific Ocean. However, there were no size-fractionated rates available for verification. Here we report the first size-fractionated new and regenerated production rates (obtained with (15)N - NO(3) and (15)N - NH(4) incubations) for the EUZ with the objective of validating the conceptual basis and functioning of the CoSINE model. Specifically, the larger phytoplankton ( with cell diameters > 5 mu m) had greater rates of new production and higher f-ratios (i.e., the proportion of NO(3) to the sum of NO(3) and NH(4) uptake) than the picoplankton that had high rates of NH(4) uptake and low f-ratios. The way that the larger primary producers are regulated in the EUZ is discussed using a continuous chemostat approach. This combines control of Si(OH)(4) production by supply rate (bottom-up) and control of growth rate ( or dilution) by grazing ( top-down control).

Projecting a relevant "next": Instruction sequences in driving lessons

Car interaction and the organisation of multi-activity in cars have become a fertile topic of research within CA and EM (Laurier 2005, Haddington & Keisanen 2009). While previous research has focused exclusively on everyday car rides, in this paper we will analyse a specific kind of car interaction, namely driving lessons. In addition to"driving" and"talking", as the two main parallel activities in everyday car rides (Mondada in press), in driving lessons a central activity is"instructing", that we understand to be a collaborative accomplishment (Sanchez Svensson et al. 2009). Drawing on a corpus of 7 video-recorded driving lessons, we will analyse the sequential organisation of"instruction sequences", i.e. of those actions that are initiated by the driving instructor with a turn projecting the next relevant action to be executed by the learner. Learners carry out next actions in two different ways: a) as"single" actions (e.g. using the indicator); b) as a complex series of overlapping or parallel actions. We will show that"single" actions occur as responses to instructions concerning the learner's command of the car, while complex actions occur when the instructors formulate direction indications. The aims of our analyses are twofold. Firstly, we will analyse how instruction sequences are fitted to the emerging contingencies of the car ride (movement in space, changing environment): we will show that a) the turn format of the instruction initiation displays the degree of"urgency" of the requested action; b) learners have the possibility to start the relevant"next" before the instruction initiation comes to completion. Secondly, we will focus on those"seconds" that the driving instructor treats as problematic by initiating a repair sequence (e.g. an improper use of the indicator). Our research contributes to the discussion about the multimodal resources that participants can employ to fulfil a projected action. In addition, it offers insights in a hitherto scarcely investigated topic, namely the organisation of instructions and the ecology of apprenticeship. References HADDINGTON, P. & KEISANEN, T. (2009) Location, mobility and the body as resources in selecting a route. Journal of Pragmatics 41 (10), 1938-1961. LAURIER, Eric (2005): Searching for a parking space. Intellectica 41-42/2-3: 101-116. MONDADA, Lorenza (in press). Talking and driving: multi-activity in the car. Semiotica. SANCHEZ SVENSSON, M. et al. (2009) "Embedding instruction in practice: contingency and collaboration during surgical training", Sociology of Health & Illness, 31/6: 889-906.

Driving ability, mental illness and psychotropic medication in the elderly

Fitness to drive in elderly drivers is most commonly discussed with a focus on cognitive impairment. Therefore, this article is focussing on mental illness and the use of psychotropic drugs in elderly drivers, which can both interfere with fitness to drive. Based on a detailed literature review and on clinical judgement, we propose signposts and "red flags" to judge the individual risks. Health professionals dealing with elderly patients should in particular be aware of the dangers related to cumulative risks and need to inform the patients appropriately. For medico-legal reasons the information provided to patients must be written down in the medical record. Individual counselling is important as fitness to drive is a complex topic.

Manipulations to reduce simulator-related transient adverse health effects during simulated driving

User comfort during simulated driving is of key importance, since reduced comfort can confound the experiment and increase dropout rates. A common comfort-affecting factor is simulator-related transient adverse health effect (SHE). In this study, we propose and evaluate methods to adapt a virtual driving scene to reduce SHEs. In contrast to the manufacturer-provided high-sensory conflict scene (high-SCS), we developed a low-sensory conflict scene (low-SCS). Twenty young, healthy participants drove in both the high-SCS and the low-SCS scene for 10 min on two different days (same time of day, randomized order). Before and after driving, participants rated SHEs by completing the Simulator Sickness Questionnaire (SSQ). During driving, several physiological parameters were recorded. After driving in the high-SCS, the SSQ score increased in average by 129.4 (122.9 %, p = 0.002) compared to an increase of 5.0 (3.4 %, p = 0.878) after driving in the low-SCS. In the low-SCS, skin conductance decreased by 13.8 % (p < 0.01) and saccade amplitudes increased by 16.1 % (p < 0.01). Results show that the investigated methods reduce SHEs in a younger population, and the low-SCS is well accepted by the users. We expect that these measures will improve user comfort.

Les juifs dans l'Empire Romain : leur condition juridique, économique et sociale

par Jean Juster

Site and Age Condition the Growth Responses to Climate and Drought of Relict Pinus nigra subsp. salzmannii Populations in Southern Spain

To assess if tree age may modulate the main climatic drivers of radial growth, two relict Pinus nigra subsp. salzmannii populations (Maria, most xeric site; Magina, least xeric site) were sampled in southern Spain near the limits of the species range. Tree-ring width residual chronologies for two age groups (mature trees, age <= 100 years (minimum 40 years); old trees, age > 100 years) were built to evaluate their responses to climate by relating them to monthly precipitation and temperature and a drought index (DRI) using correlation and response functions. We found that drought is the main driver of growth of relict P. nigra populations, but differences between sites and age classes were also observed. First, growth in the most xeric site depends on the drought severity during the previous autumn and the spring of the year of tree-ring formation, whereas in the relatively more mesic site growth is mainly enhanced by warm and wet conditions in spring. Second, growth of mature trees responded more to drought severity than that of old trees. Our findings indicate that drought severity will mainly affect growth of relict P. nigra populations dominated by mature trees in xeric sites. This conclusion may also apply to similar mountain Mediterranean conifer relicts.

Determination of Δ9-tetrahydrocannabinolic acid A (Δ9-THCA-A) in whole blood and plasma by LC–MS/MS and application in authentic samples from drivers suspected of driving under the influence of cannabis

Delta-9-tetrahydrocannabinolic acid A (THCA-A) is the biosynthetic precursor of delta-9-tetrahydrocannabinol (THC) in cannabis plants, and has no psychotropic effects. THCA-A can be detected in blood and urine, and several metabolites have been identified. THCA-A was also shown to be incorporated in hair by side stream smoke to a minor extent, but incorporation via blood stream or sweat seems unlikely. The detection of THCA-A in biological fluids may serve as a marker for differentiating between the intake of prescribed THC medication – containing only pure THC – and cannabis products containing THC besides THC-acid A and other cannabinoids. However, the knowledge about its usefulness in forensic cases is very limited. The aim of the present work was the development of a reliable method for THCA-A determination in human blood or plasma using LC–MS/MS and application to cases of driving under the influence of drugs. Fifty eight (58) authentic whole blood and the respective plasma samples were collected from drivers suspected of driving under the influence of cannabis from the region of Bern (Switzerland). Samples were first tested for THC, 11-OH-THC and THC-COOH, and then additionally for THCA-A. For this purpose, the existing LC–MS/MS method was modified and validated, and found to be selective and linear over a range of 1.0 to 200 ng/mL (the correlation coefficients were above 0.9980 in all validation runs). Limit of detection (LOD) and limit of quantification (LOQ) were 0.3 ng/mL and 1.0 ng/mL respectively. Intra- and inter-assay accuracy were equal or better than 90% and intra- and inter-assay precision were equal or better than 11.1%. The mean extraction efficiencies were satisfactory being equal or higher than 85.4%. THCA-A was stable in whole blood samples after 3 freeze/thaw cycles and storage at 4 °C for 7 days. Re-injection (autosampler) stability was also satisfactory. THC was present in all blood samples with levels ranging from 0.7 to 51 ng/mL. THCA-A concentrations ranged from 1.0 to 496 ng/mL in blood samples and from 1.4 to 824 ng/mL in plasma samples. The plasma:blood partition coefficient had a mean value of 1.7 (±0.21, SD). No correlation was found between the degree of intoxication or impairment stated in the police protocols or reports of medical examinations and the detected THCA-A-concentration in blood.