Showing papers by "University of Paris published in 2001"

Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group.

Abstract: Background Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. Methods We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [–4] or lower than –3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than –4 or lower than –3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. Results Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned t...

Genotype-Phenotype Correlation in the Long-QT Syndrome Gene-Specific Triggers for Life-Threatening Arrhythmias

Abstract: Background The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific. Methods and results We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with ss-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. Conclusions Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches.

Hirschsprung disease, associated syndromes and genetics: a review

Abstract: Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.

Classification and phylogeny of hydrogenases.

Abstract: Hydrogenases (H2ases) catalyze the reversible oxidation of molecular hydrogen and play a central role in microbial energy metabolism. Most of these enzymes are found in Archaea and Bacteria, but a few are present in Eucarya as well. They can be distributed into three classes: the [Fe]-H2ases, the [NiFe]-H2ases, and the metal-free H2ases. The vast majority of known H2ases belong to the first two classes, and over 100 of these enzymes have been characterized genetically and/or biochemically. Compelling evidence from sequences and structures indicates that the [NiFe]- and [Fe]-H2ases are phylogenetically distinct classes of proteins. The catalytic core of the [NiFe]-H2ases is a heterodimeric protein, although additional subunits are present in many of these enzymes. Functional classes of [NiFe]-H2ases have been defined, and they are consistent with categories defined by sequence similarity of the catalytic subunits. The catalytic core of the [Fe]-H2ases is a ca. 350-residue domain that accommodates the active site (H-cluster). A few monomeric [Fe]-H2ases are barely larger than the H-cluster domain. Many others are monomeric as well, but possess additional domains that contain redox centers, mostly iron–sulfur. Some [Fe]-H2ases are oligomeric. The modular structure of H2ases is strikingly illustrated in recently unveiled sequences and structures. It is also remarkable that most of the accessory domains and subunits of H2ases have counterparts in other redox complexes, in particular NADH-ubiquinone oxidoreductase (Complex I) of respiratory chains. Microbial genome sequences are bringing forth a significant body of additional H2ase sequence data and contribute to the understanding of H2ase distribution and evolution. Altogether, the available data suggest that [Fe]-H2ases are restricted to Bacteria and Eucarya, while [NiFe]-H2ases, with one possible exception, seem to be present only in Archaea and Bacteria. H2ase processing and maturation involve the products of several genes which have been identified and are currently being characterized in the case of the [NiFe]-H2ases. In contrast, near to nothing is known regarding the maturation of the [Fe]-H2ases. Inspection of the currently available genome sequences suggests that the [NiFe]-H2ase maturation proteins have no similar counterparts in the genomes of organisms possessing [Fe]-H2ases only. This observation, if confirmed, would be consistent with the phylogenetic distinctiveness of the two classes of H2ases. Sequence alignments of catalytic subunits of H2ases have been implemented to construct phylogenetic trees that were found to be consistent, in the main, with trees derived from other data. On the basis of the comparisons performed and discussed here, proposals are made to simplify and rationalize the nomenclature of H2ase-encoding genes.

Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study

Abstract: Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.

Fast LTL to Büchi Automata Translation

Abstract: We present an algorithm to generate Buchi automata from LTL formulae. This algorithm generates a very weak alternating co-Buchi automaton and then transforms it into a Buchi automaton, using a generalized Buchi automaton as an intermediate step. Each automaton is simplified on-the-fly in order to save memory and time. As usual we simplify the LTL formula before any treatment. We implemented this algorithm and compared it with Spin: the experiments show that our algorithm is much more efficient than Spin. The criteria of comparison are the size of the resulting automaton, the time of the computation and the memory used. Our implementation is available on the web at the following address: http://verif.liafa.jussieu.fr/ltl2ba

FETI‐DP: a dual–primal unified FETI method—part I: A faster alternative to the two‐level FETI method

Abstract: The FETI method and its two-level extension (FETI-2) are two numerically scalable domain decomposition methods with Lagrange multipliers for the iterative solution of second-order solid mechanics and fourth-order beam, plate and shell structural problems, respectively.The FETI-2 method distinguishes itself from the basic or one-level FETI method by a second set of Lagrange multipliers that are introduced at the subdomain cross-points to enforce at each iteration the exact continuity of a subset of the displacement field at these specific locations. In this paper, we present a dual–primal formulation of the FETI-2 concept that eliminates the need for that second set of Lagrange multipliers, and unifies all previously developed one-level and two-level FETI algorithms into a single dual–primal FETI-DP method. We show that this new FETI-DP method is numerically scalable for both second-order and fourth-order problems. We also show that it is more robust and more computationally efficient than existing FETI solvers, particularly when the number of subdomains and/or processors is very large. Copyright © 2001 John Wiley & Sons, Ltd.

History of subduction and back‐arc extension in the Central Mediterranean

Abstract: SUMMARY Geological and geophysical constraints to reconstruct the evolution of the Central Mediterranean subduction zone are presented. Geological observations such as upper plate stratigraphy, HP–LT metamorphic assemblages, foredeep/trench stratigraphy, arc volcanism and the back-arc extension process are used to define the infant stage of the subduction zone and its latest, back-arc phase. Based on this data set, the time dependence of the amount of subducted material in comparison with the tomographic images of the upper mantle along two cross-sections from the northern Apennines and from Calabria to the Gulf of Lyon can be derived. Further, the reconstruction is used to unravel the main evolutionary trends of the subduction process. Results of this analysis indicate that (1) subduction in the Central Mediterranean is as old as 80 Myr, (2) the slab descended slowly into the mantle during the first 20–30 Myr (subduction speeds were probably less than 1 cm year x1 ), (3) subduction accelerated afterwards, producing arc volcanism and back-arc extension and (4) the slab reached the 660 km transition zone after 60–70 Myr. This time-dependent scenario, where a slow initiation is followed by a roughly exponential increase in the subduction speed, can be modelled by equating the viscous dissipation per unit length due to the bending of oceanic lithosphere to the rate of change of potential energy by slab pull. Finally, the third stage is controlled by the interaction between the slab and the 660 km transition zone. In the southern region, this results in an important re-shaping of the slab and intermittent pulses of back-arc extension. In the northern region, the decrease in the trench retreat can be explained by the entrance of light continental material at the trench.

Gaussian model selection

Abstract: Our purpose in this paper is to provide a general approach to model selection via penalization for Gaussian regression and to develop our point of view about this subject. The advantage and importance of model selection come from the fact that it provides a suitable approach to many different types of problems, starting from model selection per se (among a family of parametric models, which one is more suitable for the data at hand), which includes for instance variable selection in regression models, to nonparametric estimation, for which it provides a very powerful tool that allows adaptation under quite general circumstances. Our approach to model selection also provides a natural connection between the parametric and nonparametric points of view and copes naturally with the fact that a model is not necessarily true. The method is based on the penalization of a least squares criterion which can be viewed as a generalization of Mallows’Cp. A large part of our efforts will be put on choosing properly the list of models and the penalty function for various estimation problems like classical variable selection or adaptive estimation for various types of lp-bodies.

Applications of Malliavin calculus to Monte-Carlo methods in finance. II

Abstract: This paper presents an original probabilistic method for the numerical computations of Greeks (i.e. price sensitivities) in finance. Our approach is based on the {\it integration-by-parts} formula, which lies at the core of the theory of variational stochastic calculus, as developed in the Malliavin calculus. The Greeks formulae, both with respect to initial conditions and for smooth perturbations of the local volatility, are provided for general discontinuous path-dependent payoff functionals of multidimensional diffusion processes. We illustrate the results by applying the formula to exotic European options in the framework of the Black and Scholes model. Our method is compared to the Monte Carlo finite difference approach and turns out to be very efficient in the case of discontinuous payoff functionals.

Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation.

Abstract: Interferons (IFN) alpha/beta and gamma induce the formation of two transcriptional activators: gamma-activating factor (GAF) and interferon-stimulated gamma factor 3 (ISGF3). We report a natural heterozygous germline STAT1 mutation associated with susceptibility to mycobacterial but not viral disease. This mutation causes a loss of GAF and ISGF3 activation but is dominant for one cellular phenotype and recessive for the other. It impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs. Thus, the antimycobacterial, but not the antiviral, effects of human IFNs are principally mediated by GAF.

DNS-based predictive control of turbulence: an optimal benchmark for feedback algorithms

Abstract: Direct numerical simulations (DNS) and optimal control theory are used in a predictive control setting to determine controls that effectively reduce the turbulent kinetic energy and drag of a turbulent flow in a plane channel at Reτ = 100 and Reτ = 180. Wall transpiration (unsteady blowing/suction) with zero net mass flux is used as the control. The algorithm used for the control optimization is based solely on the control objective and the nonlinear partial differential equation governing the flow, with no ad hoc assumptions other than the finite prediction horizon, T, over which the control is optimized.Flow relaminarization, accompanied by a drag reduction of over 50%, is obtained in some of the control cases with the predictive control approach in direct numerical simulations of subcritical turbulent channel flows. Such performance far exceeds what has been obtained to date in similar flows (using this type of actuation) via adaptive strategies such as neural networks, intuition-based strategies such as opposition control, and the so-called ‘suboptimal’ strategies, which involve optimizations over a vanishingly small prediction horizon T+ → 0. To achieve flow relaminarization in the predictive control approach, it is shown that it is necessary to optimize the controls over a sufficiently long prediction horizon T+ [gsim ] 25. Implications of this result are discussed.The predictive control algorithm requires full flow field information and is computationally expensive, involving iterative direct numerical simulations. It is, therefore, impossible to implement this algorithm directly in a practical setting. However, these calculations allow us to quantify the best possible system performance given a certain class of flow actuation and to qualify how optimized controls correlate with the near-wall coherent structures believed to dominate the process of turbulence production in wall-bounded flows. Further, various approaches have been proposed to distil practical feedback schemes from the predictive control approach without the suboptimal approximation, which is shown in the present work to restrict severely the effectiveness of the resulting control algorithm. The present work thus represents a further step towards the determination of optimally effective yet implementable control strategies for the mitigation or enhancement of the consequential effects of turbulence.

Noninvasive versus conventional mechanical ventilation. An epidemiologic survey.

Abstract: used in 14% of patients with hypoxemic ARF, in 27% of those with pulmonary edema, and in 50% of those with hypercapnic ARF. NIV was followed by ETI in 40% of cases. The incidence of both nosocomial pneumonia (10% versus 19%, p 5 0.03), and mortality (22% versus 41%, p , 0.001) was lower in NIV patients than in those with ETI. After adjusting for differences at baseline, Simplified Acute Physiology Score (SAPS) II (odds ratio [OR] 5 1.05 per point; confidence interval [CI]: 1.04 to 1.06), McCabe/Jackson score (OR 5 2.18; CI: 1.57 to 3.03), and hypoxemic ARF (OR 5 2.30; CI: 1.33 to 4.01) were identified as risk factors explaining mortality; success of NIV was associated with a lower risk of pneumonia (OR 5 0.06; CI: 0.01 to 0.45) and of death (OR 5 0.16; CI: 0.05 to 0.54). In NIV patients, SAPS II and a poor clinical tolerance predicted secondary ETI. Failure of NIV was associated with a longer length of stay. In conclusion, NIV can be successful in selected patients, and is associated with a lower risk of pneumonia and death than is ETI. Noninvasive ventilation (NIV) has been shown in randomized controlled trials to be efficient for reducing the need for endotracheal intubation (ETI) in several groups of patients with acute respiratory failure (ARF) (1‐5). Patients with acute-onchronic respiratory failure are the most likely to benefit from NIV in terms of morbidity and mortality (1, 6). Selected patients with various forms of hypoxemic respiratory failure may also benefit from NIV in terms of intubation rate and complications (2). In this category of patients, however, the results are more variable (7, 8), which may be explained by the type of patients, the location at which treatment is provided, or the skill of the care team. Careful studies of the nursing and therapist workload required to deliver NIV suggest that this technique requires specific training, and that its efficacy probably follows a learning curve (9‐11). When the investigators who conducted these studies computed the specific time required to treat patients with NIV, they found that in the first hours of treatment, more time was required of the respiratory therapists than with a conventional approach (10, 11). The careful selection of patients, as well as the nonblinded nature of the clinical trials of NIV, are among the factors that could explain why the results of randomized controlled trials may differ slightly from those of everyday practice. For this reason, it appears important to assess the use and efficacy of NIV not only through clinical trials but also in everyday practice. We thus conducted an observational survey in France among 42 intensive care units (ICUs) to evaluate the use of NIV and to assess its efficacy in everyday clinical practice by comparing patients with similar etiologies treated with either NIV or ETI, after adjusting for the severity of their illness. METHODS

Deterministic Observation Theory and Applications

Abstract: 1. Introduction Part I. Observability and Observers: 2. Observability concepts 3. The case dy <= du 4. The case of dy < du 5. Singular state-output mappings 6. Observers: the high-gain construction Part II. Dynamic Output Stabilization and Applications: 7. Dynamic output stabilization 8. Applications 9. Appendix 10. Solutions to the exercises of Part I Bibliography Index.

Electrochemical biosensors: recommended definitions and classification*

Abstract: *A special report on the International Union of Pure and Applied Chemistry, Physical Chemistry Division, Commission I.7 (Biophysical Chemistry), Analytical Chemistry Division, Commission V.5 (Electroanalytical Chemistry).

Ram Pressure Stripping and Galaxy Orbits: The Case of the Virgo Cluster

Abstract: We investigate the role of ram pressure stripping in the Virgo Cluster using N-body simulations. Radial orbits within the Virgo Cluster's gravitational potential are modeled and analyzed with respect to ram pressure stripping. The N-body model consists of 10,000 gas cloud complexes that can have inelastic collisions. Ram pressure is modeled as an additional acceleration on the clouds located at the surface of the gas distribution in the direction of the galaxy's motion within the cluster. We made several simulations, changing the orbital parameters in order to recover different stripping scenarios using realistic temporal ram pressure profiles. We investigate systematically the influence of the inclination angle between the disk and the orbital plane of the galaxy on the gasdynamics. We show that ram pressure can lead to a temporary increase of the central gas surface density. In some cases a considerable part of the total atomic gas mass (several 108 M☉) can fall back onto the galactic disk after the stripping event. A quantitative relation between the orbit parameters and the resulting H I deficiency is derived containing explicitly the inclination angle between the disk and the orbital plane. The comparison between existing H I observations and the results of our simulations shows that the H I deficiency depends strongly on galaxy orbits. It is concluded that the scenario in which ram pressure stripping is responsible for the observed H I deficiency is consistent with all H I 21 cm observations in the Virgo Cluster.

Mutations in CGI-58, the Gene Encoding a New Protein of the Esterase/Lipase/Thioesterase Subfamily, in Chanarin-Dorfman Syndrome

Abstract: Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma (NCIE) that is characterized by the presence of intracellular lipid droplets in most tissues. We previously localized a gene for a subset of NCIE to chromosome 3 (designated “the NCIE2 locus”), in six families. Lipid droplets were found in five of these six families, suggesting a diagnosis of CDS. Four additional families selected on the basis of a confirmed diagnosis of CDS also showed linkage to the NCIE2 locus. Linkage-disequilibrium analysis of these families, all from the Mediterranean basin, allowed us to refine the NCIE2 locus to an ∼1.3-Mb region. Candidate genes from the interval were screened, and eight distinct mutations in the recently identified CGI-58 gene were found in 13 patients from these nine families. The spectrum of gene variants included insertion, deletion, splice-site, and point mutations. The CGI-58 protein belongs to a large family of proteins characterized by an α/β hydrolase fold. CGI-58 contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. Interestingly, CGI-58 differs from other members of the esterase/lipase/thioesterase subfamily in that its putative catalytic triad contains an asparagine in place of the usual serine residue.

Liver hanging maneuver: a safe approach to right hepatectomy without liver mobilization.

Abstract: In right hepatectomy the complete mobilization of the liver before parenchymal transection is considered as a basic maneuver for a safe procedure. When a huge tumor invades the diaphragm, liver mobilization may be difficult. In these cases Lai and coworkers reported an “anterior approach” with parenchymal transection from the anterior surface down to the IVC. The absence of liver rotation has many advantages. It may avoid tumor dissemination and requires no compression of the remnant liver. Because it may be difficult to control bleeding in the deeper parenchymal plane we propose a new technique of hanging the liver after lifting it with a tape passed between the anterior surface of the IVC and the liver parenchyma.

Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts.

Abstract: The concept of contrast imaging was introduced to ultrasound almost 30 years ago. The development of ultrasound contrast agents (USCAs), initially slowed by technical limitations, has become more dynamic during the past decade. The ideal USCA should be non-toxic, injectable intravenously, capable of crossing the pulmonary capillary bed after a peripheral injection, and stable enough to achieve enhancement for the duration of the examination. While satisfying cost–benefit requirements, it should provide not only Doppler but also gray-scale enhancement. Already, Doppler examinations are improved by using USCAs when studying deep and small vessels, vessels with low or slow flow, or vessels with a non-optimal insonation angle. Ultrasound contrast agents also enhance detection of flow within abnormal vessels, including tumor vascularization and stenotic vessels, and provide better delineation of ischemic areas. Research is focusing on the development of specific contrast imaging sequences that allow detection of tissue enhancement similar to that obtained with CT or MRI. These sequences take advantage of the non-linear behavior of the microbubbles within the ultrasound field, bringing real-time perfusion imaging for liver, kidney, and the myocardium into reach. New objectives include targeted agents that could further widen USCA applications to specific delivery of active drugs such as anticoagulants or cytotoxic compounds. The combination of new generations of USCAs and new ultrasound image sequences appears to be very promising and currently represents a significant part of ultrasound research.

Plasmid-mediated extended-spectrum β-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1

Abstract: Six non-clonally related enterobacterial isolates producing a same extended-spectrum β-lactamase CTX-M-15 were isolated in 1999 from patients hospitalized in a New Delhi hospital. CTX-M-15 differed from CTX-M-3 by an asparagine to glycine substitution in position ABL238. Its gene was located on large plasmids varying in size. In each case, a same insertion sequence ISEcp1 was identified upstream of the 5′ end of blaCTX-M-15. Typical −35 and −10 promoter sequences of Enterobacteriaceae were identified in the 3′ end of ISEcp1. The location of ISEcp1 upstream of plasmid-mediated CTX-M-type β-lactamase genes may contribute to their spread or/and their expression.

Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria

Abstract: Human mature erythrocytes have been considered as unable to undergo programmed cell death (PCD), due to their lack of mitochondria, nucleus and other organelles, and to the finding that they survive two conditions that induce PCD in vitro in all human nucleated cells, treatment with staurosporine and serum deprivation. Here we report that mature erythrocytes can undergo a rapid self-destruction process sharing several features with apoptosis, including cell shrinkage, plasma membrane microvesiculation, phosphatidylserine externalization, and leading to erythrocyte disintegration, or, in the presence of macrophages, to macrophage ingestion of dying erythrocytes. This regulated form of PCD was induced by Ca2+ influx, and prevented by cysteine protease inhibitors that allowed erythrocyte survival in vitro and in vivo. The cysteine proteinases involved seem not to be caspases, since (i) proforms of caspase 3, while present in erythrocytes, were not activated during erythrocyte death; (ii) cytochrome c, a critical component of the apoptosome, was lacking; and (iii) cell-free assays did not detect activated effectors of nuclear apoptosis in dying erythrocytes. Our findings provide the first identification that a death program can operate in the absence of mitochondria. They indicate that mature erythrocytes share with all other mammalian cell types the capacity to self-destruct in response to environmental signals, and imply that erythrocyte survival may be modulated by therapeutic intervention. Cell Death and Differentiation (2001) 8, 1143–1156

Severe pulmonary embolism associated with air travel.

Abstract: Background Air travel is believed to be a risk factor for pulmonary embolism, but the relation between pulmonary embolism and distance flown has not been documented. The aim of this study was to investigate whether the duration of air travel is related to the risk of pulmonary embolism. Methods From November 1993 to December 2000, we systematically reviewed all cases of pulmonary embolism requiring medical care on arrival at France's busiest international airport. Data on the geographic origins of all flights and the numbers of passengers were collected in order to evaluate the incidence of pulmonary embolism per million passenger arrivals as a function of the distance traveled. Results A total of 135.29 million passengers from 145 countries or other areas arrived at Charles de Gaulle Airport during the period of the study, of whom 56 had confirmed pulmonary embolism. The incidence of pulmonary embolism was much higher among passengers traveling more than 5000 km (3100 mi) (1.5 cases per million, as compa...