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Whereas hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in menopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required at both a cellular and molecular level. Both the endothelium and the immuno-inflammatory system play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it rather elicits a pro-inflammatory response in vivo at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. E2 promotes beneficial actions on the endothelium such as nitric oxide and prostacyclin production. E2 actions are essentially mediated by two molecular targets: estrogen receptor α (ER-α) and β (ER-β), but the former appears to mediate most of the actions of E2 on the endothelium and on the immune system. ER-α modulates target gene transcription through two activation functions (AF), AF-1 and AF-2, even though signalling via ER-α located at the plasma membrane (responsible for membrane-initiated steroid signalling (MISS)/(extra-genomic)) can also lead to an indirect effect on gene transcription. Recently, we demonstrated that ER-α AF-1 is not required for the vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. These results suggest that selective estrogen receptor modulators stimulating ER-α with minimal activation of ER-α AF-1 could retain beneficial vascular actions, while minimizing the sexual effects. [ABSTRACT FROM AUTHOR]

Improved laws, enhanced enforcement, and public awareness brought about by citizens' concern, during the 1980s led to dramatic declines in drinking and driving in the industrialized world. The declines included about 50% in Great Britain, 28% in The Netherlands, 28% in Canada, 32% in Australia, 39% in France, 37% in Germany, and 26% in the United States. Some of these declines may be due in part to lifestyle changes, demographic shifts, and economic conditions. In most countries the declines reversed in the early 1990s and drinking and driving began to increase. By the middle of that decade the increases stabilized and the rates of drinking and driving again began to decline. These decreases were much less dramatic than those in the 1980s. Approaching the end of the 1990s and early in the new century, the record has been mixed. Some countries (France and Germany (until 2002)) continued to reduce drinking and driving while in other countries (Canada, the Netherlands, Great Britain, and the United States), there was stagnation and in some cases small increases or even large increase as was the case in Sweden. Complacency and attention to other issues in recent years have been difficult to overcome in some countries. Harmonization of traffic safety laws in the European Union has strengthened laws in some countries but threatens existing strong policies in others. It may be that the major gains have already been made and that additional progress will require a much greater level of scientific knowledge, use of new and emerging technologies, and political and social commitment to put in place proven countermeasures. [ABSTRACT FROM AUTHOR]

Twelve subjects drove on a closed 5-km track until they fell asleep behind the wheel or quitted for other reasons. The instances of falling asleep occurred after 7 to 12 hours of driving. Falling asleep could be characterized by nodding of the head, closing of the eyes and the car continuing in its previous course. On none of these occasions did the experimenter have to take over the control of the car and all subjects woke by themselves. The average duration between three instances of falling asleep was 24 min. After a break with a brisk walk the subjects fell asleep again after an average of 23 min. Two preceding sessions of 3 hours of driving on a motorway with subsidiary reaction time measurements predicted (r= — 0·72 and —0·17) the endurance on the closed track. [ABSTRACT FROM PUBLISHER]

Indirect psychological or physiological measures of driving performance are often used without supporting evidence, or even comment, on their validity. In this validation the performance of ten subjects on a subsidiary reaction time (RT) task and a visual detection task was correlated. On the RT task, 93 dB auditory signals were presented with an average intersignal interval of SO s. On the detection task, the subjects had to brake as fast as possible when they perceived a 40 × 40 cm obstacle at the side of the road. Over the test of three hours, in night driving conditions on a closed 5 km track, the correlation between group averages was —0.78 and the average within-subject correlation was —0.47. From these results, and a discussion of the predictive and the construct validity of the RT-task, it is concluded that subsidiary RT may be used as a valid indicator of changes in efficiency of driving performance. [ABSTRACT FROM PUBLISHER]

A reaction time (RT) task was used in three conditions, each lasting 2 h, during which six female subjects: (i) drove on a 5 km closed track, (ii) were driven as passenger on the same track, and (iii) were tested in a stationary vehicle. There was an increase in RT only in the driving condition. Furthermore, there was a progressively greater increase in RT over the three successive test sessions, independent of the order in which conditions were tested. Measurement of hoart-rato (HE) showed that HR deereasod only in the driving and the passenger conditions, and that the docreaso in HR became progressively smaller over the three sossions. Consequently RT-data and HR-data (interpreted as indicating lovel of arousal) provided contra-indications of changes in driving proficiency. [ABSTRACT FROM PUBLISHER]

From accident statistics a difference was hypothesized between experienced and inexperienced drivers in vulnerability to continuous driving. This difference was used as a basis for a comparison of changes in autonomic measures and reaction time over driving time. The result showed significant effects of experience on both types of measures. Heart-rate pointed to experienced and reaction time pointed to inexperienced drivers as being the most vulnerable to continuous driving. This contradiction was solved with reference to statistical data and validation of the reaction time task. Thus in this study reaction time was preferred to the autonomic measures [ABSTRACT FROM PUBLISHER]