Haben selektive COX-2-Hemmer unerwünschte renale und kardiovaskuläre Wirkungen [Do selective COX-2 inhibitors have adverse renal and cardiovascular effects?].

Selective cyclooxygenase-2-inhibitors (COX-2) were developed as an alternative to the non-steroidal anti-inflammatory drugs (NSAID) in order to reduce their known gastrointestinal and renal toxicity. Several recent studies have shown the complex mechanism of the cyclooxygenase-2. The inhibition of the COX-2 has effects on renal hemodynamics, renal salt and water retention and may increase the thromboembolic and therefore the cardiovascular risk. The renal toxicity of the COX-2 inhibitors is similar to that of traditional NSAID. Regarding these data, COX-2 inhibitors should be prescribed with much caution to high risk patients, that is, patients with renal failure and/or cardiovascular diseases.

The Lausanne cohort Lc65+: a population-based prospective study of the manifestations, determinants and outcomes of frailty

BACKGROUND: Frailty is a relatively new geriatric concept referring to an increased vulnerability to stressors. Various definitions have been proposed, as well as a range of multidimensional instruments for its measurement. More recently, a frailty phenotype that predicts a range of adverse outcomes has been described. Understanding frailty is a particular challenge both from a clinical and a public health perspective because it may be a reversible precursor of functional dependence. The Lausanne cohort Lc65+ is a longitudinal study specifically designed to investigate the manifestations of frailty from its first signs in the youngest old, identify medical and psychosocial determinants, and describe its evolution and related outcomes. METHODS/DESIGN: The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). The baseline data collection was completed among 1422 participants in 2004-2005 through questionnaires, examination and performance tests. It comprised a wide range of medical and psychosocial dimensions, including a life course history of adverse events. Outcomes measures comprise subjective health, limitations in activities of daily living, mobility impairments, development of medical conditions or chronic health problems, falls, institutionalization, health services utilization, and death. Two additional random samples of 65-70 years old subjects will be surveyed in 2009 (birth year 1939-1943) and in 2014 (birth year 1944-1948). DISCUSSION: The Lc65+ study focuses on the sequence "Determinants --> Components --> Consequences" of frailty. It currently provides information on health in the youngest old and will allow comparisons to be made between the profiles of aging individuals born before, during and at the end of the Second World War.

Exposition à des particules virales aéroportées potentiellement pathogènes dans des abattoirs et dans la filière du tri des déchets

La caractérisation de l'exposition à des bioaérosols dans différents secteurs de travail a, durant de nombreuses années, été documentée principalement pour les icroorganismes cultivables tels que les bactéries et les champignons. Puis, le développement des méthodes moléculaires d'analyse de l'ADN par amplification de séquences spécifiques ou universelles par PCR(1) a permis une caractérisation beaucoup plus réaliste des expositions en tenant compte, non seulement des bactéries et champignons cultivables, mais aussi des non-cultivables qui représentent l'immense majorité des icroorganismes totaux présents dans l'air. Ainsi, depuis une dizaine d'années, nos connaissances sur les communautés bactériennes et fongiques aéroportées se sont élargies (1). Aujourd'hui, une nouvelle avancée est faite, grâce à la métagénomique(2) qui permet d'identifier (après ou non amplification de l'ADN total) une grande part des séquences d'ADN présentes dans un environnement (2). L'utilisation de la PCR(1) et/ou de la métagénomique(2), dans le domaine de la santé au travail, s'est jusqu'à présent limitée à la caractérisation de l'exposition aux bactéries et champignons laissant de côté les virus. Cependant, il s'avère que beaucoup de virus pathogènes se transmettent par voie aérienne et qu'un grand nombre de travailleurs manipulent des matières pouvant être contaminées. C'est le cas des employés des abattoirs, potentiellement exposés à des virus zoonotiques(3) et des employés d'usines de tri des déchets ménagers solides. Cette note décrit deux études qui ont évalué, pour la première fois dans ces secteurs de travail, l'exposition professionnelle à des particules virales, la première en utilisant la métagénomique(2) et la seconde en utilisant les méthodes PCR(1) classique.

Propagation du virus de la grippe dans les transports aériens et survie du virus dans l'air ambiant

Chaque hiver en France, la grippe saisonnière touche entre 2 et 7 millions de personnes, dont environ 1 000 cas mortels, surtout parmi les personnes de plus de 65 ans. Elle constitue ainsi la première cause de mortalité par maladie infectieuse. L'agent causal est un virus à ARN très contagieux, pouvant appartenir à différent type (A, B ou C). Le type A est composé d'une large gamme de sous-types classés selon les différentes sortes et associations de protéines de surface du virus. Parmi ceux-ci, les sous-types H1N1 et H3N2 circulent actuellement chez l'Homme. La transmission inter-humaine de la maladie se fait principalement par voie aéroportée par le biais des gouttelettes riches en virus provenant des accès de toux et des éternuements des sujets infectés. Le coût sanitaire et social annuel de la grippe est estimé à 460 millions d'euros pour une épidémie moyenne. La prévention de la grippe repose sur une vaccination annuelle, proposée dans la plupart des pays industrialisés aux personnes à risque. Cependant, la couverture vaccinale en France n'était que de 23 % de la population générale en 2011-2012 (62 % chez les plus de 50 ans). Dès lors, environ 80 % des individus sont susceptibles de contracter la maladie. Les transports en commun constituent des environnements idéaux pour la dissémination des virus. En effet, la grande promiscuité entre les passagers potentiellement malades et les passagers sains favorise la propagation de la maladie. Dans ces conditions, l'évaluation du risque d'infection est utile pour appliquer une prévention ciblée. Le but du premier article analysé (Gupta et al., 2012) était, précisément, d'évaluer le risque, pour un passager sain, de contracter le virus de la grippe dans un avion transportant un passager malade. Les auteurs du second article analysé (Pyankov et al., 2012) ont estimé le temps de survie de différents sous-types de virus de la grippe dans l'air ambiant d'une chambre expérimentale.

Patient with syncope and LQTS carrying a mutation in the PAS domain of the hERG1 channel.

We report the case of a woman with syncope and persistently prolonged QTc interval. Screening of congenital long QT syndrome (LQTS) genes revealed that she was a heterozygous carrier of a novel KCNH2 mutation, c.G238C. Electrophysiological and biochemical characterizations unveiled the pathogenicity of this new mutation, displaying a 2-fold reduction in protein expression and current density due to a maturation/trafficking-deficient mechanism. The patient's phenotype can be fully explained by this observation. This study illustrates the importance of performing genetic analyses and mutation characterization when there is a suspicion of congenital LQTS. Identifying mutations in the PAS domain or other domains of the hERG1 channel and understanding their effect may provide more focused and mutation-specific risk assessment in this population.

Dose optimization approach to fast X-ray microtomography of the lung alveoli.

A basic prerequisite for in vivo X-ray imaging of the lung is the exact determination of radiation dose. Achieving resolutions of the order of micrometres may become particularly challenging owing to increased dose, which in the worst case can be lethal for the imaged animal model. A framework for linking image quality to radiation dose in order to optimize experimental parameters with respect to dose reduction is presented. The approach may find application for current and future in vivo studies to facilitate proper experiment planning and radiation risk assessment on the one hand and exploit imaging capabilities on the other.

Biomechanical wall properties of human intracranial aneurysms resected following surgical clipping (IRRAs Project)

Background and purpose: Individual rupture risk assessment of intracranial aneurysms is a major issue in the clinical management of asymptomatic aneurysms. Aneurysm rupture occurs when wall tension exceeds the strength limit of the wall tissue. At present, aneurysmal wall mechanics are poorly understood and thus, risk assessment involving mechanical properties is inexistent. Aneurysm computational hemodynamics studies make the assumption of rigid walls, an arguable simplification. We therefore aim to assess mechanical properties of ruptured and unruptured intracranial aneurysms in order to provide the foundation for future patient-specific aneurysmal risk assessment. This work also challenges some of the currently held hypotheses in computational flow hemodynamics research. Methods: A specific conservation protocol was applied to aneurysmal tissues following clipping and resection in order to preserve their mechanical properties. Sixteen intracranial aneurysms (11 female, 5 male) underwent mechanical uniaxial stress tests under physiological conditions, temperature, and saline isotonic solution. These represented 11 unruptured and 5 ruptured aneurysms. Stress/strain curves were then obtained for each sample, and a fitting algorithm was applied following a 3-parameter (C(10), C(01), C(11)) Mooney-Rivlin hyperelastic model. Each aneurysm was classified according to its biomechanical properties and (un)rupture status.Results: Tissue testing demonstrated three main tissue classes: Soft, Rigid, and Intermediate. All unruptured aneurysms presented a more Rigid tissue than ruptured or pre-ruptured aneurysms within each gender subgroup. Wall thickness was not correlated to aneurysmal status (ruptured/unruptured). An Intermediate subgroup of unruptured aneurysms with softer tissue characteristic was identified and correlated with multiple documented risk factors of rupture. Conclusion: There is a significant modification in biomechanical properties between ruptured aneurysm, presenting a soft tissue and unruptured aneurysms, presenting a rigid material. This finding strongly supports the idea that a biomechanical risk factor based assessment should be utilized in the to improve the therapeutic decision making.

Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation.

BACKGROUND: Toll-like receptors (TLRs) are essential components of the immune response to fungal pathogens. We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients of allogeneic hematopoietic-cell transplants. METHODS: We analyzed 20 single-nucleotide polymorphisms (SNPs) in the toll-like receptor 2 gene (TLR2), the toll-like receptor 3 gene (TLR3), the toll-like receptor 4 gene (TLR4), and the toll-like receptor 9 gene (TLR9) in a cohort of 336 recipients of hematopoietic-cell transplants and their unrelated donors. The risk of invasive aspergillosis was assessed with the use of multivariate Cox regression analysis. The analysis was replicated in a validation study involving 103 case patients and 263 matched controls who received hematopoietic-cell transplants from related and unrelated donors. RESULTS: In the discovery study, two donor TLR4 haplotypes (S3 and S4) increased the risk of invasive aspergillosis (adjusted hazard ratio for S3, 2.20; 95% confidence interval [CI], 1.14 to 4.25; P=0.02; adjusted hazard ratio for S4, 6.16; 95% CI, 1.97 to 19.26; P=0.002). The haplotype S4 was present in carriers of two SNPs in strong linkage disequilibrium (1063 A/G [D299G] and 1363 C/T [T399I]) that influence TLR4 function. In the validation study, donor haplotype S4 also increased the risk of invasive aspergillosis (adjusted odds ratio, 2.49; 95% CI, 1.15 to 5.41; P=0.02); the association was present in unrelated recipients of hematopoietic-cell transplants (odds ratio, 5.00; 95% CI, 1.04 to 24.01; P=0.04) but not in related recipients (odds ratio, 2.29; 95% CI, 0.93 to 5.68; P=0.07). In the discovery study, seropositivity for cytomegalovirus (CMV) in donors or recipients, donor positivity for S4, or both, as compared with negative results for CMV and S4, were associated with an increase in the 3-year probability of invasive aspergillosis (12% vs. 1%, P=0.02) and death that was not related to relapse (35% vs. 22%, P=0.02). CONCLUSIONS: This study suggests an association between the donor TLR4 haplotype S4 and the risk of invasive aspergillosis among recipients of hematopoietic-cell transplants from unrelated donors.

Beliefs about and attitudes toward gambling in French-speaking Switzerland.

The present study aims to analyze attitudes and beliefs of the French-speaking general Swiss population (n = 2500; female n = 1280; mean age = 43 years) as regards gambling, which are to date almost exclusively studied in the North American and Australian contexts. Beliefs related to gambling include the perception of the effectiveness of preventive measures toward gambling, the comparative risk assessment of different addictive behaviors, the perceived risks of different types of gambling and attitudes are related to the gambler's personality. The general population perceived gambling rather negatively and was conscious of the potential risks of gambling; indeed, 59.0% of the sample identified gambling as an addictive practice. Slot machines were estimated to bear the highest risk. Compared with women and older people, men and young people indicated more positive beliefs about gambling; they perceived gambling as less addictive, supported structural preventive measures less often, and perceived gambling as a less serious problem for society. Gamblers were more likely to put their practices into perspective, perceiving gambling more positively than non-gamblers. General population surveys on such beliefs can deliver insights into preventive actions that should be targeted to young men who showed more favorable views of gambling, which have been shown to be associated with increased risk for problematic gambling.

FRAX® International Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

Osteoporosis is a serious worldwide epidemic. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors and femoral neck BMD and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. The International Society for Clinical Densitometry (ISCD) in conjunction with the International Osteoporosis Foundation (IOF) assembled an international panel of experts that ultimately developed joint Official Positions of the ISCD and IOF advising clinicians regarding FRAX® usage. As part of the process, the charge of the FRAX® International Task Force was to review and synthesize data regarding geographic and race/ethnic variability in hip fractures, non-hip osteoporotic fractures, and make recommendations about the use of FRAX® in ethnic groups and countries without a FRAX® calculator. This synthesis was presented to the expert panel and constitutes the data on which the subsequent Official Positions are predicated. A summary of the International Task Force composition and charge is presented here.

Wavelet analysis residual kriging vs. neural network residual kriging

This paper deals with the problem of spatial data mapping. A new method based on wavelet interpolation and geostatistical prediction (kriging) is proposed. The method - wavelet analysis residual kriging (WARK) - is developed in order to assess the problems rising for highly variable data in presence of spatial trends. In these cases stationary prediction models have very limited application. Wavelet analysis is used to model large-scale structures and kriging of the remaining residuals focuses on small-scale peculiarities. WARK is able to model spatial pattern which features multiscale structure. In the present work WARK is applied to the rainfall data and the results of validation are compared with the ones obtained from neural network residual kriging (NNRK). NNRK is also a residual-based method, which uses artificial neural network to model large-scale non-linear trends. The comparison of the results demonstrates the high quality performance of WARK in predicting hot spots, reproducing global statistical characteristics of the distribution and spatial correlation structure.

Parameter estimation for the distribution of single cell lag times.

In Quantitative Microbial Risk Assessment, it is vital to understand how lag times of individual cells are distributed over a bacterial population. Such identified distributions can be used to predict the time by which, in a growth-supporting environment, a few pathogenic cells can multiply to a poisoning concentration level. We model the lag time of a single cell, inoculated into a new environment, by the delay of the growth function characterizing the generated subpopulation. We introduce an easy-to-implement procedure, based on the method of moments, to estimate the parameters of the distribution of single cell lag times. The advantage of the method is especially apparent for cases where the initial number of cells is small and random, and the culture is detectable only in the exponential growth phase.

An Illustrated Guide for Monitoring and Protecting Bridge Waterways Against Scour - Project TR-515 - Final Report, March 2006

This report is a well illustrated and practical Guide intended to aid engineers and engineering technicians in monitoring, maintaining, and protecting bridge waterways so as to mitigate or prevent scour from adversely affecting the structural performance of bridge abutments, piers, and approach road embankments. Described and illustrated here are the scour processes affecting the stability of these components of bridge waterways. Also described and illustrated are methods for monitoring waterways, and the various methods for repairing scour damage and protecting bridge waterways against scour. The Guide focuses on smaller bridges, especially those in Iowa. Scour processes at small bridges are complicated by the close proximity of abutments, piers, and waterway banks, such that scour processes interact in ways difficult to predict and for which reliable design relationships do not exist. Additionally, blockage by woody debris or by ice, along with changes in approach channel alignment, can have greater effects on pier and abutment scour for smaller bridges. These considerations tend to cause greater reliance on monitoring for smaller bridges. The Guide is intended to augment and support, as a source of information, existing procedures for monitoring bridge waterways. It also may prompt some adjustments of existing forms and reports used for bridge monitoring. In accord with increasing emphasis on effective management of public facilities like bridges, the Guide ventures to include an example report format for quantitative risk assessment applied to bridge waterways. Quantitative risk assessment is useful when many bridges have to be evaluated for scour risk and damage, and priorities need to be determined for repair and protection work. Such risk assessment aids comparison of bridges at risk. It is expected that bridge inspectors will implement the Guide as a concise, handy reference available back at the office. The Guide also likely may be implemented as an educational primer for new inspectors who have yet to become acquainted with waterway scour. Additionally, the Guide may be implemented as a part of process to check whether existing bridge-inspection forms or reports adequately encompass bridge-waterway scour.