Syndromes cliniquement isolés dans l'accident vasculaire cérébral

Chaque année, près de 14000 personnes sont victimes d'un accident vasculaire cérébral (AVC) en Suisse (1). Parmi elles, 3000-4000 individus décèdent des suites de leur attaque et environ 2000 personnes survivent avec des séquelles qui peuvent être relativement importantes. Cette affection a donc un poids non négligeable en terme de morbidité et de mortalité ; dans les pays indistrualisés, elle représente la première cause de handicap, la deuxième cause de démence ainsi que la troisième cause de mortalité. Il existe deux types d'AVC : les accidents ischémiques et les accidents hémorragiques (2,3). Dans environ 80% des cas, les AVC sont des accidents ischémiques, résultant d'une occlusion artérielle ou veineuse - les ischémies sur occlusion veineuse étant rares en comparaison de celles sur occulsion artérielle. En outre, on parle d'accident ischémiques transitoires (AIT) lorsque les symptomes sont spontanément résolutifs en moins de 24 heures. Les accidents hémorragiques, quant à eux, ne constituent qu'une minorité des AVC (20%) et sont secondaires à une rupture de vaisseau. La physiopathologie des différents types d'AVC a été particulièrement bien étudiée, ce qui a permis de mettre en évidence un certain nombre de causes. Un AVC peut donc être d'origine cardiaque (embole à point de départ cardiaque, fibrillation auriculaire), d'origine athéromateuse (embole sur plaque d'athéromatose des vaisseaux pré-cérébraux) ou encore, la conséquence directe d'une hypertension artérielle (maladie des petits vaisseaux, hémorragies intracérébrales) (3). Il existe également des causes un peu moins fréquentes, telles que les dissections aortiques, les ruptures d'anévrisme, les malformations artério-veineuses, les états pro-coagulants, les vasculites, la prise de toxiques. De nombreux facteurs de risque ont été mis en évidence (3). Certains d'entre eux, tels que l'âge, le sexe ou l'éthnie, ne sont pas modifiables. Mais il en est d'autres sur lesquels il est possible d'avoir un impact positif et leur identification fait donc partie intégrante du bilan de base chez les patients victimes d'AVC. Il s'agit de l'hypertension artérielle, du diabète, du tabagisme actif et de l'hypercholestérolémie. La présentation clinique de l'AVC est fonction du territoire vasculaire touché (3). Historiquement, la localisation et la compréhension des fonctions cérébrales ont été le fruit de corrélations anatomo-clinique puis radiologico-clinique (2). Dans la majorité des cas, on étudiait la partie commune à toutes les lésions de différents patients présentant un symptôme, et cette partie était présumée responsable de cette fonction. Néanmoins, le patient pouvait présenter d'autres symptômes associés, ce qui peut représenter un certain biais. A l'heure actuelle, l'imagerie fonctionnelle remplace progressivement ces corrélations radiologico- cliniques (2). Finalement, des études de cas isolés, avec lésions relativement circonscrites, ont également contribués à la compréhension des fonctions cérébrales (4-12). Le but principal de cette étude est d'analyser les syndromes cliniquement isolées (CIS, atteinte d'une fonction cérébrale, d'un segment corporel) dans le registre lausannois des accidents vasculaires cérébraux en terme de facteurs de risques, et de caractéristiques de l'AVC (origine, localisation) afin de déterminer des facteurs indépendants de survenue de telles atteintes, d'un point de vue général et pour chacune d'entre elles.

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system.

Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts.

Discounting Spotted Apples: Investigating Consumers’ Willingness to Accept Cosmetic Damage in an Organic Product, November 2006

Organic producers have limited methods of avoiding plant diseases that result in cosmetic damage to produce. Therefore, the appearance of organic produce is often less than perfect. We use an experimental auction to investigate how cosmetic damage affects consumers’ willingness to pay for organic apples. We find that 75% of the participants are willing to pay more for organic than for conventional apples given identical appearance. However, at the first sight of any imperfection in the appearance of the organic apples, this segment is significantly reduced. Furthermore, we find that there is a significant effect of interaction between cosmetic damage and product methods. Even though most consumers say they buy organic products to avoid pesticides, we find that cosmetic damage has a larger impact on the willingness to pay for organic apples than for conventional apples.

Une cause exceptionnelle d'hypertension artérielle de l'enfant : l'artérite de Takayasu [An exceptional cause of arterial hypertension in children: Takayasu arteritis].

Takayasu arteritis, a nonspecific inflammatory arteritis, is particularly rare in children. We report the case of a 6-year-old girl presenting with severe arterial hypertension in the upper segment associated with an inflammatory syndrome. Investigations showed coarctation of the abdominal aorta at different levels, due to Takayasu arteritis. The patient was treated with percutaneous dilatation and stent implantation as well as prolonged anti-inflammatory therapy. Arterial hypertension in children needs to be investigated until its cause, which may be rare such as Takaysu arteritis, is determined.

Age-related differences in the use of guideline-recommended medical and interventional therapies for acute coronary syndromes: a cohort study.

OBJECTIVES: To compare the use of guideline-recommended medical and interventional therapies in older and younger patients with acute coronary syndromes (ACSs). DESIGN: Prospective cohort study. SETTING: Fifty-five hospitals in Switzerland. PARTICIPANTS: Eleven thousand nine hundred thirty-two patients with ACS enrolled between March 1, 2001, and June 30, 2006. ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA). MEASUREMENTS: Use of medical and interventional therapies was determined after exclusion of patients with contraindications and after adjustment for comorbidities. Multivariate logistic regression models were used to calculate odds ratios (ORs) per year increase in age. RESULTS: Elderly patients were less likely to receive acetylsalicylic acid (OR=0.976, 95% confidence interval (CI)=0.969-0.980) or beta-blockers (OR=0.985, 95% CI=0.981-0.989). No age-dependent difference was found for heparin use. Elderly patients with STEMI were less likely to receive percutaneous coronary intervention (PCI) or thrombolysis (OR=0.955, 95% CI=0.949-0.961). Elderly patients with NSTEMI or UA less often underwent PCI (OR=0.943, 95% CI=0.937-0.949). CONCLUSION: Elderly patients across the whole spectrum of ACS were less likely to receive guideline-recommended therapies, even after adequate adjustment for comorbidities. Prognosis of elderly patients with ACS may be improved by increasing adherence to guideline-recommended medical and interventional therapies.

Life expectancy with and without disability

Average life expectancy reached 78.8 years in Europe in 2002 (WHO 2003); most Europeans can, therefore, now anticipate living well past 75 years of age. Projections in industrialized nations suggest a continuing mortality decline in the next decades 1 while birth rates will probably continue to decline, resulting in further ageing of these nations. As those aged 80 years and over are the fastest expanding segment of the older population, concerns are growing about a potential dramatic increase in the number of disabled persons. The ageing of the population and the related increase in chronic disease burden have already had major impacts on most Western health-care systems, and will probably further affect these systems in the future as the baby-boom generation becomes older. For instance, in Switzerland, it is estimated that costs due to long-term care could more than double by 2030, from 6.5 to 15.3 billion SFr.2 Similar trends are expected in most European countries. As a consequence, postponement of the onset of disability, with a compression of functional dependency into a shorter period towards the end of life, is becoming a major goal. To successfully achieve this goal and improve the control of growing health and social care expenditures, various strategies of health promotion and disease prevention are developed and tested. Although several of these experiences had some effects on functional decline and institutional placement, they have not been shown to be cost-effective. Additional strategies are, therefore, needed to prevent or delay the onset of disability in older persons, reduce functional impairment, and face the challenge of an increasing disabled elderly population.

Lane Closure Policy Development, Enforcement, and Exceptions: A Survey of Seven State Transportation Agencies, February 2007

Traffic volume increases and an aging infrastructure create the need for reconstruction, rehabilitation, and maintenance of existing facilities. As more motorists feel that delays should be minimal during highway renewal projects, lane closures that reduce capacity through the work zone should not create unreasonable delays. In order to facilitate the determination of when a lane closure is permitted during the day, some state transportation agencies (STAs) have developed lane closure policies, or strategies, that they use as guidance in determining daily permitted lane closure times. Permitted lane closure times define what times of the day, week, or season a lane closure is allowed on a facility and at a specific location or segment. This research addresses the lane closure policies of several STAs that were reputed to have good lane closures policies or strategies and that were selected by the project advisory committee for further research.

Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value.OBJECTIVE This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers.METHODS The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2.RESULTS Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes.CONCLUSION M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family.

Pre-procés i segmentació en imatges d’ultrasons 2D i 3D de la pròstata

Aquest projecte s'ha dut a terme amb el Grup de visió per computador del departamentd'Arquitectura i Tecnologia de Computadors (ATC) de la Universitat de Girona. Està enfocat a l'anàlisi d'imatges mèdiques, en concret s'analitzaran imatges de pròstata en relació a desenvolupaments que s'estan realitzant en el grup de visió esmentat. Els objectius fixats per aquest projecte són desenvolupar dos mòduls de processamentm d'imatges els quals afrontaran dos blocs important en el tractament d'imatges, aquests dos mòduls seran un pre-processat d'imatges, que constarà de tres filtres i un bloc de segmentació per tal de cercar la pròstata dintre de les imatges a tractar. En el projecte es treballarà amb el llenguatge de programació C++, concretament amb unes llibreries que es denominen ITK (Insight Toolkit ) i són open source enfocades al tractament d'imatges mèdiques. A part d'aquesta eina s'utilitzaran d'altres com les Qt que és una biblioteca d'eines per crear entorns gràfics

Internalization and homologous desensitization of the GLP-1 receptor depend on phosphorylation of the receptor carboxyl tail at the same three sites.

Homologous desensitization and internalization of the GLP-1 receptor correlate with phosphorylation of the receptor in a 33-amino acid segment of the cytoplasmic tail. Here, we identify the sites of phosphorylation as being three serine doublets located at positions 441/442, 444/445, and 451/452. The role of phosphorylation on homologous desensitization was assessed after stable expression in fibroblasts of the wild type or of mutant receptors in which phosphorylation sites were changed in various combinations to alanines. We showed that desensitization, as measured by a decrease in the maximal production of cAMP after a first exposure of the cells to GLP-1, was strictly dependent on phosphorylation. Furthermore, the number of phosphorylation sites correlated with the extent of desensitization with no, intermediate, or maximal desensitization observed in the presence of one, two, or three phosphorylation sites, respectively. Internalization of the receptor-ligand complex was assessed by measuring the rate of internalization of bound [125I]GLP-1 or the redistribution of the receptor to an endosomal compartment after agonist binding. Our data demonstrate that internalization was prevented in the absence of receptor phosphorylation and that intermediate rates of endocytosis were obtained with receptors containing one or two phosphorylation sites. Thus, homologous desensitization and internalization require phosphorylation of the receptor at the same three sites. However, the differential quantitative impairment of these two processes in the single and double mutants suggests different molecular mechanisms controlling desensitization and internalization.

Nonsense Mutations in FAM161A Cause RP28-Associated Recessive Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a degenerative disease of the retina leading to progressive loss of vision and, in many instances, to legal blindness at the end stage. The RP28 locus was assigned in 1999 to the short arm of chromosome 2 by homozygosity mapping in a large Indian family segregating autosomal-recessive RP (arRP). Following a combined approach of chromatin immunoprecipitation and parallel sequencing of genomic DNA, we identified a gene, FAM161A, which was shown to carry a homozygous nonsense mutation (p.Arg229X) in patients from the original RP28 pedigree. Another homozygous FAM161A stop mutation (p.Arg437X) was detected in three subjects from a cohort of 118 apparently unrelated German RP patients. Age at disease onset in these patients was in the second to third decade, with severe visual handicap in the fifth decade and legal blindness in the sixth to seventh decades. FAM161A is a phylogenetically conserved gene, expressed in the retina at relatively high levels and encoding a putative 76 kDa protein of unknown function. In the mouse retina, Fam161a mRNA is developmentally regulated and controlled by the transcription factor Crx, as demonstrated by chromatin immunoprecipitation and organotypic reporter assays on explanted retinas. Fam161a protein localizes to photoreceptor cells during development, and in adult animals it is present in the inner segment as well as the outer plexiform layer of the retina, the synaptic interface between photoreceptors and their efferent neurons. Taken together, our data indicate that null mutations in FAM161A are responsible for the RP28-associated arRP.

On the distribution of income and worker assignment under intra-firm spillovers, with an application to ideas and networks

We study the earnings structure and the equilibrium assignment of workers when workers exert intra-firm spillovers on each other.We allow for arbitrary spillovers provided output depends on some aggregate index of workers' skill. Despite the possibility of increasing returns to skills, equilibrium typically exists. We show that equilibrium will typically be segregated; that the skill space can be partitioned into a set of segments and any firm hires from only one segment. Next, we apply the model to analyze the effect of information technology on segmentation and the distribution of income. There are two types of human capital, productivity and creativity, i.e. the ability to produce ideas that may be duplicated over a network. Under plausible assumptions, inequality rises and then falls when network size increases, and the poorest workers cannot lose. We also analyze the impact of an improvement in worker quality and of an increased international mobility of ideas.

A randomized concave programming method for choice network revenue management

Models incorporating more realistic models of customer behavior, as customers choosing froman offer set, have recently become popular in assortment optimization and revenue management.The dynamic program for these models is intractable and approximated by a deterministiclinear program called the CDLP which has an exponential number of columns. However, whenthe segment consideration sets overlap, the CDLP is difficult to solve. Column generationhas been proposed but finding an entering column has been shown to be NP-hard. In thispaper we propose a new approach called SDCP to solving CDLP based on segments and theirconsideration sets. SDCP is a relaxation of CDLP and hence forms a looser upper bound onthe dynamic program but coincides with CDLP for the case of non-overlapping segments. Ifthe number of elements in a consideration set for a segment is not very large (SDCP) can beapplied to any discrete-choice model of consumer behavior. We tighten the SDCP bound by(i) simulations, called the randomized concave programming (RCP) method, and (ii) by addingcuts to a recent compact formulation of the problem for a latent multinomial-choice model ofdemand (SBLP+). This latter approach turns out to be very effective, essentially obtainingCDLP value, and excellent revenue performance in simulations, even for overlapping segments.By formulating the problem as a separation problem, we give insight into why CDLP is easyfor the MNL with non-overlapping considerations sets and why generalizations of MNL posedifficulties. We perform numerical simulations to determine the revenue performance of all themethods on reference data sets in the literature.

A tractable consideration set structure for network revenue management

Models incorporating more realistic models of customer behavior, as customers choosing from an offerset, have recently become popular in assortment optimization and revenue management. The dynamicprogram for these models is intractable and approximated by a deterministic linear program called theCDLP which has an exponential number of columns. When there are products that are being consideredfor purchase by more than one customer segment, CDLP is difficult to solve since column generationis known to be NP-hard. However, recent research indicates that a formulation based on segments withcuts imposing consistency (SDCP+) is tractable and approximates the CDLP value very closely. In thispaper we investigate the structure of the consideration sets that make the two formulations exactly equal.We show that if the segment consideration sets follow a tree structure, CDLP = SDCP+. We give acounterexample to show that cycles can induce a gap between the CDLP and the SDCP+ relaxation.We derive two classes of valid inequalities called flow and synchronization inequalities to further improve(SDCP+), based on cycles in the consideration set structure. We give a numeric study showing theperformance of these cycle-based cuts.

A new compact linear programming formulation for choice network revenue management

The choice network revenue management model incorporates customer purchase behavioras a function of the offered products, and is the appropriate model for airline and hotel networkrevenue management, dynamic sales of bundles, and dynamic assortment optimization.The optimization problem is a stochastic dynamic program and is intractable. A certainty-equivalencerelaxation of the dynamic program, called the choice deterministic linear program(CDLP) is usually used to generate dyamic controls. Recently, a compact linear programmingformulation of this linear program was given for the multi-segment multinomial-logit (MNL)model of customer choice with non-overlapping consideration sets. Our objective is to obtaina tighter bound than this formulation while retaining the appealing properties of a compactlinear programming representation. To this end, it is natural to consider the affine relaxationof the dynamic program. We first show that the affine relaxation is NP-complete even for asingle-segment MNL model. Nevertheless, by analyzing the affine relaxation we derive a newcompact linear program that approximates the dynamic programming value function betterthan CDLP, provably between the CDLP value and the affine relaxation, and often comingclose to the latter in our numerical experiments. When the segment consideration sets overlap,we show that some strong equalities called product cuts developed for the CDLP remain validfor our new formulation. Finally we perform extensive numerical comparisons on the variousbounds to evaluate their performance.