Improvement of walking speed prediction by accelerometry and altimetry, validated by satellite positioning.

Activity monitors based on accelerometry are used to predict the speed and energy cost of walking at 0% slope, but not at other inclinations. Parallel measurements of body accelerations and altitude variation were studied to determine whether walking speed prediction could be improved. Fourteen subjects walked twice along a 1.3 km circuit with substantial slope variations (-17% to +17%). The parameters recorded were body acceleration using a uni-axial accelerometer, altitude variation using differential barometry, and walking speed using satellite positioning (DGPS). Linear regressions were calculated between acceleration and walking speed, and between acceleration/altitude and walking speed. These predictive models, calculated using the data from the first circuit run, were used to predict speed during the second circuit. Finally the predicted velocity was compared with the measured one. The result was that acceleration alone failed to predict speed (mean r = 0.4). Adding altitude variation improved the prediction (mean r = 0.7). With regard to the altitude/acceleration-speed relationship, substantial inter-individual variation was found. It is concluded that accelerometry, combined with altitude measurement, can assess position variations of humans provided inter-individual variation is taken into account. It is also confirmed that DGPS can be used for outdoor walking speed measurements, opening up new perspectives in the field of biomechanics.

Mise au point concernantl'utilisation du dosagede l'antigène carcino-embryonnaire (CEA)en clinique

The carcinoembryonic antigen (CEA) is a tumor marker defined by specific heterologous antisera. Elevated levels of circulating CEA have been detected by radioimmunoassay in 20-90 per cent of cases of colorectal carcinomas depending on the degree of tumor spread. The fact that elevation of CEA level can also be observed in other types of carcinomas and in several non malignant conditions greatly limit the value of the CEA test for the early diagnosis of colorectal carcinoma. Thus, the CEA assay should not be used as a screening test for cancer. Repeatecl CEA mesurements, however, appear to be of importance for the evaluation of tumor resection and the detection of tumor recurrence. The only localized tumors known to produce elevation of CEA above the levels observed in non malignant diseases are carcinomas of the large bowel and the pancreas. In carcinomas derived from other organs a marked increase of CEA level is always associated with the presence of distant metastasis. Therefore at the present time the clinical applications of the CEA radioimmunoassay should be limited to the differentiai diagnosis of patients with suspicion of primary colorectal or pancreatic carcinoma, to the detection of distant metastasis in other types of carcinomas and to the post operative follow up of patients who had elevated levels of CEA before surgery. Well-controlled studies are still needed to determine if therapeutic decisions based on CEA results can lead to improved survival.

The positioning of colectomy in the treatment of ulcerative colitis in the era of biologic therapy.

The position of surgery in the treatment of ulcerative colitis (UC) has changed in the era of biologics. Several important questions arise in determining the optimal positioning of surgery in the treatment of UC, which has long been a challenge facing gastroenterologists and surgeons. Surgery is life-saving in some patients and leads to better bowel function and better quality of life in most patients. The benefits of surgery, however, must be weighed against the potential surgical morbidity and compromised functioning that clearly can occur. The introduction of biologic therapy has added further complexity to decisions about medical management, surgery, and the relative timing of these choices. Appropriate medical management of UC may induce and maintain remission and may prevent surgery. However, medical management also carries risks of adverse effects, and recent data suggest that delay of surgery during ineffective medical therapy can increase the chances of negative surgical outcomes. To make individualized timely treatment decisions, early collaboration between gastroenterologists and surgeons is important and more data on predictors of treatment response and positive outcomes are needed. Early identification of patients who would benefit from biologic therapy or surgery is challenging.

Oral flurbiprofen metabolic ratio assessment using a single-point dried blood spot.

We investigated whether a single blood measurement using the minimally invasive technique of a finger prick to draw a blood sample of 5 µl (to yield a dried blood spot (DBS)) is suitable for the assessment of flurbiprofen (FLB) metabolic ratio (MR). Ten healthy volunteers who had been genotyped for CYP2C9 were recruited as subjects. They received FLB alone in session 1 and FLB with fluconazole in session 2. In session 3, the subjects were pretreated for 4 days with rifampicin and received FLB with the last dose of rifampicin on day 5. Plasma and DBS samples were obtained between 0 and 8 h after FLB administration, and urine was collected during the 8 h after administration. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. FLB's apparent clearance values decreased by 35% in plasma and DBS during session 2 and increased by 75% in plasma and by 30% in DBS during session 3. Good correlations were observed between MRs calculated from urine, plasma, and DBS samples.

Phosphorylation of CARMA1 by HPK1 is critical for NF-kappaB activation in T cells.

Activation of the NF-kappaB pathway in T cells is required for induction of an adaptive immune response. Hematopoietic progenitor kinase (HPK1) is an important proximal mediator of T-cell receptor (TCR)-induced NF-kappaB activation. Knock-down of HPK1 abrogates TCR-induced IKKbeta and NF-kappaB activation, whereas active HPK1 leads to increased IKKbeta activity in T cells. Yet, the precise molecular mechanism of this process remains elusive. Here, we show that HPK1-mediated NF-kappaB activation is dependent on the adaptor protein CARMA1. HPK1 interacts with CARMA1 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARMA1. Interestingly, the putative HPK1 phosphorylation sites in CARMA1 are different from known PKC consensus sites. Mutations of residues S549, S551, and S552 in CARMA1 abrogated phosphorylation of a CARMA1-linker construct by HPK1 in vitro. In addition, CARMA1 S551A or S5549A/S551A point mutants failed to restore HPK1-mediated and TCR-mediated NF-kappaB activation and IL-2 expression in CARMA1-deficient T cells. Thus, we identify HPK1 as a kinase specific for CARMA1 and suggest HPK1-mediated phosphorylation of CARMA1 as an additional regulatory mechanism tuning the NF-kappaB response upon TCR stimulation.

Représentations sociales et représentations intimes de la maladie. Quelques réflexions d'un clinicien [Social and private representations of cancer. A clinician's point of view]

This paper discusses social representations in scientific communications and private ones that are linked to the individual imagination. Social representations, in a limited sense, are useful for the development of preventive messages, but of little benefit to clinical work. We highlight some non-explicit aspects of scientific discourse that impact on treatment: projected beliefs and values. We tackle the relationship between the concepts of representation, imagination, identity and temporality in the individual approach of the cancer patient.

Monsieur le Minotaure et son point de vue

Les visions hallucinées de Friedrich Dürrenmatt, l'un des plus importants écrivains suisses de l'après-guerre, au travers des dessins et des manuscrits consacrés aux mythes de la Pythie, du Minotaure et de Midas. L'itinéraire créatif de Friedrich Dürrenmatt, outre sa production littéraire bien connue, est constellé d'une intense activité de peintre, de dessinateur et de graveur sur cuivre, activité qui délimite un important terrain de confrontation des pensées et des thèmes caractérisant sa recherche. Ce volume, qui accompagne l'exposition organisée par le célèbre architecte tessinois Mario Botta, présente une sélection de dessins et de notes de voyage appartenant à la collection privée de Charlotte Kerr-Dürrenmatt. Ceux-ci ont trait aux mythes de la Pythie, du Minotaure et de Midas, auxquels Dürrenmatt a consacré tant de réflexions. Les thèmes de la mythologie grecque ont toujours été présents dans la recherche de l'auteur sur la condition humaine, au point qu'il en est parfois arrivé à se représenter, de manière autobiographique, comme le protagoniste des événements décrits. Ces oeuvres revêtent une importance fondamentale car elles mettent en valeur l'importance et la signification que l'écrivain attribue à cette activité, considérée comme " mineure " par la critique mais qu'il faut en revanche interpréter comme un complément important des métaphores écrites auxquelles renvoie toute sa pensée.

Endocardite infectieuse: mise au point [Infective endocarditis: update]

The pathogenesis of infective endocarditis (IE) is being dissected at the molecular level, which should help redefine new preventive and therapeutic strategies against IE. In spite of improving health care, the incidence of IE has not decreased over the last decades. While classical predisposing conditions such as rheumatic heart disease were being eradicated, new features of IE have emerged. These include IE in intravenous drug users, IE in elderly patients with sclerotic valve disease, prosthetic valve IE and nosocomial IE. The epidemiology, pathogenesis, diagnosis, prevention and treatment of IE are being reviewed in this article.

High-precision dating and origin of synsedimentary volcanism in the Late Carboniferous Salvan-Dorenaz basin (Aiguilles-Rouges Massif, Western Alps)

Late Variscan volcanic activity is documented in the Late Carboniferous Salvan-Dorenaz sedimentary basin and in the neighboring basement units of the Aiguilles-Rouges and Mont-Blanc crystalline massifs (Western Alps). Precise U/Pb isotopic dating, zircon morphology and geochemical analyses indicate that volcanism occurred during short-lived pulses and that coexisting crustal and mantle sources were involved in the production of melts. Volcanic and subvolcanic products were emplaced along major N-S to NNE-SSW transtensional fracture zones, similar to the ones that governed intense basement exhumation and that favored the formation and filling of the Late Carboniferous Salvan-Dorenaz continental basin. In the Aiguilles-Rouges massif, dacitic flows outcropping at the base of the Salvan-Dorenaz basin erupted at 308 +/- 3 Ma; they represent the surface equivalent of the nearby Vallorcine peraluminous granite and associated rhyolitic dykes (311 +/- 17 Ma). In the Mont Blanc massif, calc-alkaline rhyolitic dykes were emplaced simultaneously (307 +/- 2 Ma) at shallow crustal levels, but they derive from deeper magma sources denoting enhanced mantellic activity. Recently identified tuffs and volcaniclastic layers embedded at different levels of the Salvan-Dorenaz stratigraphic record testify a 295 +3/-4 Ma old episode of highly explosive volcanism from distant volcanic centers, possibly located in the Aar-Gotthard massifs (Central Alps). Their zircon typology is highly heterogeneous. documenting wall-rock contamination of the melts and/or admixture of crustal sediments, whereas consistent subpopulations point to high-temperature magmas of deep-seated origin and alkaline affinity. The dated volcanic layers from the Salvan-Dorenaz basin set the beginning of the detrital sedimentation at 308 +/- 3 Ma and constrain the deposition of 1.5-1.7 km thick of elastic sediments within a time span of 10-15 Ma. These results infer minimum, long-term subsidence rates during basin evolution in the order of >0.1 mm/a, while in the surrounding basement units estimated exhumation rates are in the range of 1 mm/a. All dated rocks contain inherited zircon populations about 350, 450 or 600 Ma old.