Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study.

PURPOSE: To evaluate a diagnostic strategy for pulmonary embolism that combined clinical assessment, plasma D-dimer measurement, lower limb venous ultrasonography, and helical computed tomography (CT). METHODS: A cohort of 965 consecutive patients presenting to the emergency departments of three general and teaching hospitals with clinically suspected pulmonary embolism underwent sequential noninvasive testing. Clinical probability was assessed by a prediction rule combined with implicit judgment. All patients were followed for 3 months. RESULTS: A normal D-dimer level (<500 microg/L by a rapid enzyme-linked immunosorbent assay) ruled out venous thromboembolism in 280 patients (29%), and finding a deep vein thrombosis by ultrasonography established the diagnosis in 92 patients (9.5%). Helical CT was required in only 593 patients (61%) and showed pulmonary embolism in 124 patients (12.8%). Pulmonary embolism was considered ruled out in the 450 patients (46.6%) with a negative ultrasound and CT scan and a low-to-intermediate clinical probability. The 8 patients with a negative ultrasound and CT scan despite a high clinical probability proceeded to pulmonary angiography (positive: 2; negative: 6). Helical CT was inconclusive in 11 patients (pulmonary embolism: 4; no pulmonary embolism: 7). The overall prevalence of pulmonary embolism was 23%. Patients classified as not having pulmonary embolism were not anticoagulated during follow-up and had a 3-month thromboembolic risk of 1.0% (95% confidence interval: 0.5% to 2.1%). CONCLUSION: A noninvasive diagnostic strategy combining clinical assessment, D-dimer measurement, ultrasonography, and helical CT yielded a diagnosis in 99% of outpatients suspected of pulmonary embolism, and appeared to be safe, provided that CT was combined with ultrasonography to rule out the disease.

Profiling of T-cell receptor signaling complex assembly in human CD4 T-lymphocytes using RP protein arrays.

The RP protein (RPP) array approach immobilizes minute amounts of cell lysates or tissue protein extracts as distinct microspots on NC-coated slide. Subsequent detection with specific antibodies allows multiplexed quantification of proteins and their modifications at a scale that is beyond what traditional techniques can achieve. Cellular functions are the result of the coordinated action of signaling proteins assembled in macromolecular complexes. These signaling complexes are highly dynamic structures that change their composition with time and space to adapt to cell environment. Their comprehensive analysis requires until now relatively large amounts of cells (>5 x 10(7)) due to their low abundance and breakdown during isolation procedure. In this study, we combined small scale affinity capture of the T-cell receptor (TCR) and RPP arrays to follow TCR signaling complex assembly in human ex vivo isolated CD4 T-cells. Using this strategy, we report specific recruitment of signaling components to the TCR complex upon T-cell activation in as few as 0.5 million of cells. Second- to fourth-order TCR interacting proteins were accurately quantified, making this strategy specially well-suited to the analysis of membrane-associated signaling complexes in limited amounts of cells or tissues, e.g., ex vivo isolated cells or clinical specimens.

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Stable isotope composition of smectite in suevites at the Ries crater, Germany: Implications for hydrous alteration of impactites

The 24-km diameter Ries crater, Germany, exhibits well-preserved crater filling and surficial melt-rich breccia deposits that are believed to have been altered by post-impact hydrothermal fluids. The alteration mineralogy of the crater filling breccias is characterized by clay (smectite, chlorite) and a zeolite assemblage, and secondary clay phases (smectite, minor halloysite) in surficial melt-bearing breccia deposits. Using stable isotope analysis of secondary smectitic clay fractions, evidence of significant hydrous alteration of impactites at large water/rock ratios was found. The estimated fluid temperatures, using data derived by delta(18)O and delta D fractionation, suggest smectite precipitation in surficial breccias in equilibrium with meteoric fluids at temperatures 16 +/- 5 degrees C in agreement with the long-term variation of modern precipitation in the area. The stable isotope composition of smectite in crater-fill breccia, however, suggests a trend of monotonously increasing temperatures from 43 to 112 degrees C. with increasing depth through the breccia sequence. This demonstrates a different origin of alteration and temperature distribution for the surficial and crater filling melt-bearing impact breccias in the Ries crater. Our results suggest that the inverted structure of hydrothermal systems observed in some terrestrial impact craters, including the Ries crater, could indicate the initial configuration of a thermal anomaly in the crater filling sequence, but which is replaced with a normal hydrothermal convection in crater proper, during the course of post-impact cooling. (C) 2010 Elsevier B.V. All rights reserved.

Neige, blanc, papier. Poésie et arts visuels à l'âge contemporain

La neige, dans ses dimensions optiques, chromatiques et plastiques, dans ses états instables et variables, constitue l'un des enjeux centraux de l'esthétique contemporaine,. Neige blanc papier fait l'historiographie des esthétiques de la neige, de la quête d'un art pur, affranchi de toute contrainte illustrative, littéraire, voire représentative, à la construction de formes expressives où se réinvente un langage-espace. Au coeur du volume, le calepin d'artiste réalisé par la plasticienne Catherine Bolle, Inhumaine neige lunel, concrétise à son tour l'imaginaire poétique de la neige dans la matérialité esthétique du livre.

Policy Shocks and Contract Renegotiation: Who Gets Raked Over the Coals?

Changes in climate policy have large influence on businesses. Firms anticipate and respond to such changes, but what if they have already engaged in a longterm relationship with other firms or customers at the time of policy change? For example, coal supply to power stations is typically based on long-term contracts, while the nature of the buyer-supplier relationship may well be affected substantially by climate regulations. However, there has been little evidence on whether or how firms amend their contractual agreements in response to a change in policy.

Activation of HTLV-I transcription in the presence of Tax is independent of the acetylation of CREB-2 (ATF-4).

We have previously demonstrated that the bZIP transcription factor CREB-2, also called ATF-4, trans-activates, in association with the viral protein Tax, the human T-cell leukemia virus type I (HTLV-I) promoter. In this study, we have examined whether CREB-2 acetylation affects transcriptional activation mediated by Tax. We present evidence that CREB-2 is acetylated in vitro and in vivo. CREB-2 is acetylated in two regions: the basic domain of the bZIP (from amino acid residue 270 to 300) and the short basic domain (from 342 to 351) located downstream from the bZIP. We also demonstrate that CREB-2 is acetylated by p300/CBP but not by p/CAF. Moreover, replacement of lysine by arginine in the basic domains decreases the trans-activating capacity of CREB-2. However, in the presence of Tax, the HTLV-I transcription remains fully activated by these CREB-2 mutants. Although we cannot totally exclude that the mutations could also affect CREB-2 structure and activity independent of acetylation, our results suggest that activation of the viral promoter in the presence of Tax is independent of the CREB-2 acetylation.

Rosickyite (monoclinic gamma-sulphur) from La Presta Asphalt Mine, Neuchatel, Switzerland: new X-ray powder diffraction data

Rosickyite, the natural monoclinic gamma -form of sulphur, exists in only a few localities around the globe. In the old asphalt mine at La Presta, Neuchatel. Switzerland, rosickyite occurs locally as small, but very well formed crystals suitable for crystallographic studies. It grows as an alteration product of pyrite-rich asphalt. Rosickyite from La Presta mine is pure molecular sulphur, as revealed by gas chromatography-mass spectrometry. The X-ray powder diffraction data of La Presta rosickyite does not match the one previously published for this species. Therefore, a single crystal study was undertaken and a new indexed X-ray powder diffraction diagram for natural rosickyite is proposed.

Self-perceived health status and mental health outcomes in young adults born with less than 1000 g.

AIM: To assess self-perceived health status and mental health outcomes of former extremely low-birth-weight (ELBW) infants at young adulthood compared with community norms and to analyse predictors of poor outcome. METHODS: Fifty-five ELBW adults, 18 men (33%), with median (range) gestational age of 28.7 (25.0-34.0) weeks and birth weight of 930 (680-990) grams, born in Switzerland, were included. They self-rated their health status and mental health at a mean (range) age of 23.3 (21.8-25.9) years. Health status was measured by the Medical Outcomes Study Short Form-36 questionnaire and mental health by the Brief Symptom Inventory. RESULTS: The mean scores for both outcome measures were in the normal range. However, the study group self-rated significantly higher physical health status and lower mental health status compared with the community norms, and scores for self-perceived mental health tended to be worse in the former. ELBW adults reported more problems in socio-emotional role functioning compared with the community norms. Female sex was associated with poorer and bronchopulmonary dysplasia with better mental health status. CONCLUSION: Health status and mental health of former ELBW adults were overall satisfying. However, the comparison with the community norms revealed differences, which may be important for parental and patient counselling and developing support strategies.

Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells.

NK T cells produce cytokines when their semi-invariant TCR engages glycolipids associated with CD1d. The physiological consequences of NKT cell activation remain controversial, although they have been implicated in control of autoimmunity, parasites and tumors. We show here that specific activation of NKT cells in liver and spleen leads to a rapid induction of extensive NK cell proliferation and cytotoxicity. This NK cell activation is dependent, at least in part, on IFN-gamma production by NKT cells and IL-12 production by antigen-presenting cells. Remarkably, activation of NK cells by NKT cells is highly selective, since bystander T and B lymphocytes show transient expression of activation markers but almost no proliferation. Collectively our data suggest that CD1d-dependent NKT cells regulate innate immunity by sampling blood-borne glycolipid antigens and rapidly activating NK cells.

Loss of connexin40 is associated with decreased endothelium-dependent relaxations and eNOS levels in the mouse aorta.

Upon agonist stimulation, endothelial cells trigger smooth muscle relaxation through the release of relaxing factors such as nitric oxide (NO). Endothelial cells of mouse aorta are interconnected by gap junctions made of connexin40 (Cx40) and connexin37 (Cx37), allowing the exchange of signaling molecules to coordinate their activity. Wild-type (Cx40(+/+)) and hypertensive Cx40-deficient mice (Cx40(-/-)), which also exhibit a marked decrease of Cx37 in the endothelium, were used to investigate the link between the expression of endothelial connexins (Cx40 and Cx37) and endothelial nitric oxide synthase (eNOS) expression and function in the mouse aorta. With the use of isometric tension measurements in aortic rings precontracted with U-46619, a stable thromboxane A(2) mimetic, we first demonstrate that ACh- and ATP-induced endothelium-dependent relaxations solely depend on NO release in both Cx40(+/+) and Cx40(-/-) mice, but are markedly weaker in Cx40(-/-) mice. Consistently, both basal and ACh- or ATP-induced NO production were decreased in the aorta of Cx40(-/-) mice. Altered relaxations and NO release from aorta of Cx40(-/-) mice were associated with lower expression levels of eNOS in the aortic endothelium of Cx40(-/-) mice. Using immunoprecipitation and in situ ligation assay, we further demonstrate that eNOS, Cx40, and Cx37 tightly interact with each other at intercellular junctions in the aortic endothelium of Cx40(+/+) mice, suggesting that the absence of Cx40 in association with altered Cx37 levels in endothelial cells from Cx40(-/-) mice participate to the decreased levels of eNOS. Altogether, our data suggest that the endothelial connexins may participate in the control of eNOS expression levels and function.

The Vth "prapāṭhaka" of the Vādhūlaśrautasūtra

Résumé/Summary : La thèse présentée ici et intitulée The Vth prapāṭhaka of the Vādhūlaśrautasūtra consiste en une édition critique suivie d'une traduction et d'un commentaire du Ve chapitre (prapāṭhaka) du Vādhūlaśrautasūtra consacré au sacrifice animal dit "indépendant" (nirūḍhapaśubandha) de la religion védique. La traduction et le commentaire font l'objet du premier tome de cette thèse et l'édition critique celui du second tome. Le commentaire qui suit la traduction dans le premier tome ne se limite pas aux particularités de la version Vādhūla du nirūḍhapaśubandha. Il s'agit plutôt d'une série de monographies consacrées à des aspects particuliers du sacrifice animal décrit par les Veda, voire à des questions plus générales d'exégèse des textes védiques. Dans ma conclusion à la fin du premier tome je discute aussi de l'antiquité de l'école Vādhūla et de sa place dans le corpus textuel de la branche Taittirīya du Yajurveda noir. THE PRESENT THESIS, ENTITLED THE VTH PRAPAṭHAKA OF THE VADHULASRAUTASUTRA, CONSISTS IN A CRITICAL EDITION, FOLLOWED BY A TRANSLATION AND A COMMENTARY, OF THE VTH CHAPTER (PRAPAṭHAKA) OF THE VADHULASRAUTASUTRA. THE VTH PRAPAṭHAKA IS DEDICATED TO THE DESCRIPTION OF THE SO-CALLED "INDEPENDENT" ANIMAL SACRIFICE (NIRUḍHAPASUBANDHA) IN VEDIC RELIGION. THE TRANSLATION AND THE COMMENTARY ARE PRESENTED IN THE FIRST VOLUME, WHILE THE CRITICAL EDITION MAKES UP THE SECOND VOLUME. The commentary that follows the translation in the first volume is not concerned only with the peculiarities of the Vādhūla version of the nirūḍhapaśubandha. It is more a series of short monographs related to particular aspects of the animal sacrifice described in the Veda and to problems of exegesis of Vedic texts. In my conclusion at the end of the first volume, I also discuss the ancientness of the Vādhūla school, as well as its place within the corpus of Taittirīya texts.