Platelet inhibition by low-dose aspirin but not by clopidogrel reduces the axon-reflex current-induced vasodilation in humans

We previously showed a prolonged inhibition of current-induced vasodilation (CIV) after a single oral high dose of aspirin. In this study, we tested the hypothesis of platelet involvement in CIV. Nine healthy volunteers took 75 mg aspirin/day, 98 mg of clopidogrel bisulfate/day, or placebo for 4 days. CIV was induced by two consecutive 1-min anodal current applications (0.08 mA/cm2) through deionized water with a 10-min interval. CIV was measured with laser Doppler flowmetry and expressed as a percentage of baseline cutaneous vascular conductance: %Cb. In a second experiment in 10 volunteers, aspirin and placebo were given as in experiment 1, but a 26-h delay from the last aspirin intake elapsed before ACh iontophoresis and postocclusive hyperemia were studied in parallel to CIV. In experiment 1, the means ± SE amplitude of CIV was 822 ± 314, 313 ± 144, and 746 ± 397%Cb with placebo, aspirin (P < 0.05 from placebo and clopidogrel), and clopidogrel (NS from placebo), respectively. In experiment 2, CIV impairment with aspirin was confirmed: CIV amplitudes were 300 ± 99, and 916 ± 528%Cb under aspirin and placebo, respectively (P < 0.05), whereas vasodilation to ACh iontophoresis (322 ± 74 and 365 ± 104%Cb) and peak postocclusive hyperemia (491 ± 137 and 661 ± 248%Cb) were not different between aspirin and placebo, respectively. Low-dose aspirin, even 26 h after oral administration, impairs CIV, while ACh-mediated vasodilation and postocclusive hyperemia are preserved. If platelets are involved in the neurovascular mechanism triggered by galvanic current application in humans, it is likely to occur through the cyclooxygenase but not the ADP pathway. a significant increase in skin blood flow (SkBF) has been observed in response to non-noxious galvanic current application in humans. This current-induced vasodilation (CIV) has been described as the result of an axon reflex (3) and disappears in locally anesthetized or chronically capsaicin-treated skin. Then CIV depends on capsaicin-sensitive fibers and is an interesting model of the neurovascular interaction following non-noxious stimulation (11, 16). Prostaglandins are synthesized by cyclooxygenases (COX) and play a key role as mediators in the vascular response observed during CIV. COX are expressed in a large variety of human tissues, including endothelium, smooth muscles, nerves, and platelets (29). We recently reported a long-lasting inhibition of CIV (>5 days) following a single high (1,000 mg) oral dose of aspirin (11, 12, 40), which irreversibly blocks both isoforms of COX (COX-1 and COX-2). COX of neuronal origin does not seem responsible for this long-lasting effect (13). This long-lasting inhibition of CIV is consistent with the time required to resynthesize unblocked platelets after oral single-dose aspirin leading to the hypothesis that platelets participate in the vascular response to CIV. Indeed, a single oral high dose of aspirin irreversibly inactivates the platelet COX pathway for the duration of the life of the platelets (∼10 days) (1, 36). Indomethacin, a nonspecific COX inhibitor devoid of effect on vanilloid receptors and acid-sensing ion channels (41), abolished CIV, confirming that the inhibition of CIV by aspirin likely resulted from its effect on COX (and not on vanilloid receptors or on acid-sensing ion channels). Furthermore, the specific COX-2 inhibitor, celecoxib, failed to affect CIV, suggesting that CIV is mainly a COX-1-dependent phenomenon (39). Together, with the long-lasting effect of a single oral high dose of aspirin, the fact that COX-1 isoform participates in CIV raises the question of a possible platelet involvement in the axon-reflex CIV. Although there is, to date, no in vivo proof of a direct platelet-mediated vasodilation in humans, the hypothesis of a platelet involvement in axon-reflex vasodilation and other vasodilator mechanisms has previously been explored in vitro (15, 23, 31). Those authors provided evidence for a direct in vitro platelet-mediated endothelium-dependent vasodilation in preconstricted arteries but mainly by the ADP pathway. To investigate whether the platelet COX and ADP pathways are involved in vivo in CIV, we inhibited platelet function by aspirin (a platelet COX inhibitor) or clopidogrel (a platelet ADP-receptor inhibitor). Our hypothesis was that if platelets are involved, both clopidogrel and low-dose aspirin would impair the current-induced vasodilation

VEHICLE CLASSIFICATION IN URBAN REGIONS OF THE GLOBAL SOUTH FROM AERIAL IMAGERY

Land transport is a major contributor to the human-caused climate change; knowing the total number and composition of the vehicle fleet is key for estimating its emissions. Especially for countries of the Global South, emission inventories are associated with high uncertainties because fleet data are often unknown or outdated – classifying vehicles on remote sensing has the potential to change this. We present the XWHEEL dataset based on annotated vehicles in aerial images with six classes depending on the number of wheels, size and motorization. The dataset consists of 73 annotated aerial images of the city of Dar es Salaam (Tanzania) with 15,973 vehicles. To analyze the performance of the dataset, a convolutional neural network, ReDet, and a transformer-based neural network, DINOOBB, are trained with different configurations and validated on the validation and test split, but also on aerial images from other regions. The transformer-based DINO architecture has been adapted to the remote sensing domain and modified to predict Oriented Bounding Boxes. Results show a good performance on the test split from Dar es Salaam, when the two-wheeled classes are merged and the non-motorized three-wheeled vehicles are excluded due to their rare occurrence. The best performing algorithm configurations with four classes were then tested on aerial images of Kathmandu (Nepal) and Kampala (Uganda). The performance drops for cycles and three-wheeled vehicles, as their appearance varies between countries. A main finding is that we can reliably detect the different vehicle classes in Dar es Salaam. When algorithms trained on XWHEEL are generalized to other regions of the Global South, performance decreases for the more difficult classes (bicycles and tricycles). To obtain results that are comparable across the board, we therefore recommend expanding the dataset with additional annotations from other regions of the Global South

Laser monitoring system for the CMS lead tungstate crystal calorimeter

We report on the multiple wavelength laser monitoring system designed for the CMS lead tungstate crystal calorimeter read-out with avalanche photodiodes (Barrel calorimeters) and vacuum phototriodes (End Cap calorimeters). Results are presented for the test beam performance of the system designed to achieve 0.5% relative inter-calibration of the optical transmittance for lead tungstate scintillation emission over nearly 80 000 channels. The system operates in continuous measurement cycles to follow each crystal?s evolution under irradiation and recovery periods foreseen during operation at the LHC

Chemotherapeutic errors in hospitalised cancer patients: attributable damage and extra costs

<p>Abstract</p> <p>Background</p> <p>In spite of increasing efforts to enhance patient safety, medication errors in hospitalised patients are still relatively common, but with potentially severe consequences. This study aimed to assess antineoplastic medication errors in both affected patients and intercepted cases in terms of frequency, severity for patients, and costs.</p> <p>Methods</p> <p>A 1-year prospective study was conducted in order to identify the medication errors that occurred during chemotherapy treatment of cancer patients at a French university hospital. The severity and potential consequences of intercepted errors were independently assessed by two physicians. A cost analysis was performed using a simulation of potential hospital stays, with estimations based on the costs of diagnosis-related groups.</p> <p>Results</p> <p>Among the 6, 607 antineoplastic prescriptions, 341 (5.2%) contained at least one error, corresponding to a total of 449 medication errors. However, most errors (n = 436) were intercepted before medication was administered to the patients. Prescription errors represented 91% of errors, followed by pharmaceutical (8%) and administration errors (1%). According to an independent estimation, 13.4% of avoided errors would have resulted in temporary injury and 2.6% in permanent damage, while 2.6% would have compromised the vital prognosis of the patient, with four to eight deaths thus being avoided. Overall, 13 medication errors reached the patient without causing damage, although two patients required enhanced monitoring. If the intercepted errors had not been discovered, they would have resulted in 216 additional days of hospitalisation and cost an estimated annual total of 92, 907€, comprising 69, 248€ (74%) in hospital stays and 23, 658€ (26%) in additional drugs.</p> <p>Conclusion</p> <p>Our findings point to the very small number of chemotherapy errors that actually reach patients, although problems in the chemotherapy ordering process are frequent, with the potential for being dangerous and costly.</p

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Interactions sociales et appropriation de stratégies par l'enfant pour résoudre un problème : quelles méthodes ?

Cette recherche s’inscrit dans une série de travaux recourant à une méthodologie alliant l’approche clinique piagétienne, expérimentale dans des situations différentes, et vygots-kienne, afin de mettre en évidence les processus par lesquels l’appropriation de stratégies par l’enfant sera possible par l’observation attentive de son histoire d’apprentissage et afin de comprendre un peu mieux les conditions de la mobilisation ultérieure de ces apprentissages. La méthode utilisée consiste à placer les enfants dans trois ou quatre contextes différents, à observer leurs interactions et leurs conduites cognitives, notamment en fonction de leur niveau d’expertise initial par rapport à une tâche donnée : une phase I de prétest, permettant d’apprécier le niveau initial de chaque enfant en interaction avec un adulte testeur, les enfants sont alors classés en «novices», «experts spontanés», une phase II de formation (selon des modalités qui varient) avec un adulte pour une partie des enfants novices qui deviendront ainsi des «experts formés», puis une phase III d’interaction entre «novice» et «expert» (soit spontané soit formé) et, enfin, une dernière phase IV «post-test», identique au pré-test.Tartas Valérie, Perret-Clermont Anne Nelly, Marro Pascale, Grossen Michèle. Interactions sociales et appropriation de stratégies par l’enfant pour résoudre un problème : quelles méthodes ?. In: Bulletin de psychologie, tome 57 n°469, 2004. Développement, fonctionnement : perspective historico-culturelle. pp. 111-115