Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Itinéraires : les guides de voyage en Suisse de la fin du XVIIIe siècle à 1914 : contribution à une histoire culturelle du tourisme

Menée dans une approche d'histoire culturelle, cette thèse de doctorat prend pour objet un corpus de guides de voyage en Suisse entre la fin du XVIIIe et le début du XXe siècle. Centrée sur les guides, ces livres qui entretiennent plus que d'autres des liens étroits avec le monde physique, elle a deux grands axes. Le premier est une lecture interdisciplinaire des guides de voyage, qui mêle littérature, bibliographie matérielle, histoire et histoire de l'art. Elle a cherché à comprendre les raisons et logiques du genre, en s'attachant particulièrement à ses fonctions et à ses formes (tant structurelles que textuelles et iconographiques). Cette partie de l'étude est importante, car elle n'a encore jamais été menée. Elle s'articule en deux volets : un volet théorique qui s'intéresse à l'histoire et à la forme des guides de voyage ; et une étude de cas qui s'attache à la lecture plus rapprochée de 6 guides : ceux de Thomas Martyr (1788, 1790 & 1794), Heinrich August Ottokar Reichard (1793 & 1802) et Johann Gottfried Ebel (1793, 1805, 1810-11 & 1817-18) pour la fin du XVIIIe siècle et le tournant du XIXe, et ceux de John Murray (1838 & 1886), Adolphe Joanne (1841, 1865, 1874, 1882 & 1908) et Karl Baedeker (1844, 1852, 1859, 1869, 1876, 1883, 1893, 1901 & 1913) pour le XIXe et la Belle Epoque. Le second axe de cette recherche est une réflexion sur les manières de mettre en scène l'espace dans un texte. En étudiant les itinéraires de voyage en Suisse (mais jusqu'au début du XXe siècle, « la Suisse »est pour les guides de voyage indifféremment un pays et une région supranationale : «les Alpes »), quatre types de mises en forme ont pu être identifiés : le voyage en boucle (linéaire, il part d'un point A pour y revenir), le voyage en marguerite (linéaire avec excursions), le voyage éclaté de l'ordre alphabétique, et enfin le voyage par «routes », fragments d'espace que l'on combine comme les pièces d'un puzzle, créant son chemin au fur et à mesure de sa progression. Ce faisant, on peut affirmer que les guides de voyage modernes (dont la forme se fixe dans les années 1830-1840 avec les premiers Murray, Baedeker et Joanne) se sont construits -malgré tout ce que l'on a pu dire sur la normativité prescriptive du tourisme -autour d'une liberté de plus en plus grande accordée aux voyageurs. Chacune de ces formes et chacun de ces types ayant une histoire et des conditions de possibilités, c'est en s'appuyant sur celles-ci que l'on peut mieux comprendre non seulement l'évolution du voyage et de ses pratiques, mais aussi la constitution de la forme littéraire qui l'a accompagné et permis. Ce faisant, des jalons pour une histoire culturelle du tourisme ont aussi été posés, histoire culturelle que j'appelle maintenant de mes voeux : il est quand même surprenant que, dans le pays de tourisme qu'est la Suisse, quand on s'est jusqu'à présent attaché à l'histoire du tourisme, on n'ait parlé qu'économie, société, infrastructures, loisirs ou santé, voire, plus récemment, écologie et bien-être. Redonner son creuset culturel à ce phénomène, c'est aussi retrouver une part du nôtre, car ces mémoires s'entremêlent indissociablement.

Bilateral symmetry of radial pulse in high-level tennis players: implications for the validity of central aortic pulse wave analysis.

BACKGROUND: Reconstruction of the central aortic pressure wave from the noninvasive recording of the radial pulse with applanation tonometry has become a standard tool in the field of hypertension. It is not presently known whether recording the radial pulse on the dominant or the nondominant side has any effect on such reconstruction. METHOD: We carried out radial applanation tonometry on both forearms in young, healthy, male volunteers, who were either sedentary (n = 11) or high-level tennis players (n = 10). The purpose of including tennis players was to investigate individuals with extreme asymmetry between the dominant and nondominant upper limb. RESULTS: In the sedentary individuals, forearm circumference and handgrip strength were slightly larger on the dominant (mean +/- SD respectively 27.9 +/- 1.5 cm and 53.8 +/- 10 kg) than on nondominant side (27.3 +/- 1.6 cm, P < 0.001 vs. dominant, and 52.1 +/- 11 kg, P = NS). In the tennis players, differences between sides were more conspicuous (forearm circumference: dominant 28.0 +/- 1.7 cm nondominant 26.4 +/- 1.5 cm, P < 0.001; handgrip strength 61.4 +/- 10.8 vs. 53.4 +/- 9.7 kg, P < 0.001). We found that in both sedentary individuals and tennis players, the radial pulse had identical shape on both sides and, consequently, the reconstructed central aortic pressure waveforms, as well as derived indices of central pulsatility, were not dependent on the side where applanation tonometry was carried out. CONCLUSION: Evidence from individuals with maximal asymmetry of dominant vs. nondominant upper limb indicates that laterality of measurement is not a methodological issue for central pulse wave analysis carried out with radial applanation tonometry.

The Use of Passive Samplers to Reveal Industrial and Agricultural Pollution Trends in Swiss Rivers

This study shows the efficiency of passive sampling to reveal industrial and agricultural pollution trends. Two practical applications for nonpolar and polar contaminants are presented. Low-density polyethylene (LDPE) samplers were deployed for one year in the Venoge River (VD) to monitor indicator PCBs (iPCBs, IUPAC nos. 28, 52, 101, 138, 153 and 180). The results showed that the impact of PCB emissions into the river is higher in summer than in other seasons due to the low flow rate of the river during this period. P,olar organic chemical integrative samplers (POCIS) were deployed for 4 months in the Sion-Riddes canal (VS) to investigate herbicides (terbuthylazine, diuron and linuron). Desisopropylatrazine-d5 (DIA-d5) was tested as a performance reference compound (PRC) to estimate aqueous concentration. The results showed an increase of water contamination due to the studied agricultural area. The maximal contamination was observed in April and corresponds to the period of herbicide application on the crops.

Confounding effects of heart rate on pulse wave velocity in paced patients with a low degree of atherosclerosis.

BACKGROUND: Pulse wave velocity (PWV), an index of arterial wall stiffness, is modulated by blood pressure (BP). Whether heart rate (HR) is also a modulator of PWV is controversial. Recent research involving mainly patients with high aortic PWV have found either no change or a positive correlation between the two. Given that PWV is increasingly being measured in cardiovascular studies, the relationship between HR and PWV should be known in patients with preserved arterial wall elasticity. OBJECTIVE: The aim of this study was to evaluate the importance of HR as a determinant of the variability in PWV in patients with a low degree of atherosclerosis. DESIGN AND METHODS: Fourteen patients (five female, nine male; aged 68 +/- 8 years) were evaluated post pacemaker implantation due to sick sinus or carotid hypersensitivity syndromes. Carotid-femoral PWV was measured at rest and during atrial pacing at 80, 90 and 100 bpm (paced HR). Arterial femoral blood flow (AFBF) was measured by echodoppler. RESULTS: PWV increased from 6.2 +/- 1.5 m/s (mean +/- SD) during resting sinus rhythm (HR 62 +/- 8 bpm; mean +/- SD) to 6.8 +/- 1.0, 7.0 +/- 0.9, and 7.6 +/- 1.1 m/s at pacing rates of 80, 90 and 100 bpm, respectively (P < 0.0001). Systolic (SBP) and mean blood pressure (MBP) remained constant at all HR levels, whereas AFBF increased in a linear fashion. CONCLUSIONS: These results demonstrate that even in patients with a low degree of atherosclerosis, HR is a potential modulator of carotid-femoral PWV.

Active and passive screening for tuberculosis in Vaud Canton, Switzerland

Résumé Même si l'incidence de la tuberculose est basse en Suisse, cette maladie reste un problème de santé publique en raison des migrations de populations provenant de pays où l'incidence de la tuberculose est élevée. Les immigrants, à leur arrivée en terre helvétique, doivent s'annoncer auprès d'un des cinq centres d'enregistrement pour les réfugiés (Vallorbe, Bâle, Kreuzlingen, Altstätten et Chiasso) et subir un contrôle médical qui comprend un test tuberculinique et une radiographie du thorax afin de détecter des anomalies compatibles avec une tuberculose. Les requérants avec des signes de maladie sont immédiatement pris en charge dans le but d'éviter une dissémination du bacille de Koch. Cette* étude rétrospective compare la présentation bactériologique et clinique de la tuberculose ainsi que le résultat du traitement de cette maladie chez les immigrants diagnostiqués par dépistage actif (= immigrants venant d'être enregistrés comme requérants d'asile en Suisse) avec d'autres patients diagnostiqués par dépistage passif (= patients suisses, travailleurs étrangers résidents en Suisse ainsi que d'autres étrangers incluant les touristes, les étudiants, les immigrants illégaux ainsi que 11 requérants d'asile détectés tardivement et passivement après leur entrée en Suisse). Parmi les 179 patients, 78% sont des étrangers. La médiane d'âge de la population étrangère atteinte de tuberculose est de 29 ans contre 64 ans pour les Suisses. Le dépistage actif a été effectué auprès de 71 requérants d'asile chez lesquels 49.3% [CI : 37.4 - 61.2] n'avaient pas de symptômes contre 17.6% [Cl : 10.3 - 24.9] chez les 108 passifs. La durée des symptômes était de 2 mois dans le groupe des actifs versus 2.5 mois chez les passifs (ns). L'analyse bactériologique est positive à l'examen direct ou à la culture chez 63.4% des actifs contre 70.4% des passifs (ns). La confirmation bactériologique de la tuberculose chez des patients asymptomatiques s'élevait à 42.2% [Cl : 27.2-57.2] chez les actifs contre 13% [Cl : 5.31-20.7] chez les passifs. Le plus grand danger de dissémination est couru par les patients avec un examen direct positif dont la proportion des asymptomatiques était de 22.2% ([Cl : 9.6-34.8] dans le groupe des actifs contre 11.7% [CI : 4.4-19.0] dans le groupe des passifs. Le résultat du traitement, comprenant les patients guéris (avec confirmation bactériologique de guérison) ainsi que les patients ayant accompli le traitement jusqu'à la fin (mais sans confirmation bactériologique) est similaire dans les groupes des actifs et passifs. Le résultat différent selon le statut légal avec 88% pour les travailleurs étrangers, 85% pour les Suisses, 78% pour les autres étrangers et 83% pour les réfugiés. Ces chiffres sont proches des cibles de l'OMS (85%). Le dépistage actif de la tuberculose permet la détection plus précoce des cas de tuberculose que le dépistage passif. Etant donné que les immigrants proviennent de régions où la prévalence de la tuberculose est supérieure à celle de la Suisse, ce dépistage à la frontière permet non seulement de diminuer la dissémination de cette maladie par la prise en charge immédiate des malades et de réduire la durée des symptômes mais encore de détecter des patients ne présentant aucun symptôme malgré une activité bactériologique positive. Les résultats du traitement ne satisfont pas entièrement aux exigences de l'OMS, ce qui peut être expliqué par le fait que la population de patients tuberculeux suisses étant plus âgés que celles des étrangers, le nombre de décès est plus nombreux (soit par la tuberculose, soit par les complications de maladies sous-jacentes) et que le suivi de patients étrangers est plus difficile car certains disparaissent durant le traitement et d'autres sont transférés ailleurs en Suisse ou retournent dans leur pays. Summary Aim: This retrospective study compared the bacteriological and clinical presentation of tuberculosis and the outcome of treatment in immigrant notified for TB after active screening by chest X-ray at the border with other patients detected by passive screening. Design: Retrospective study of all patients notified for TB in Vaud Canton in 2001 and 2002. Result: In Vaud Canton 78% of the 179 patients notified for TB were foreign-born. Among 71 asylum seekers actively screened at the border, 49.3% [CI 37.4 - 61.2] were symptom-free vs 17.6% [CI 10.3 - 24.9] among 108 passively screened patients. In the passively screened group, the proportion of asymptomatic patients was 15.4% for Swiss patients. 8.6% for foreign workers, and 29.4% for other foreigners. The average duration of symptoms before diagnosis among patients with complaints was 2 months in actively screened foreign-born, compared to 2.5 months in passively screened patients (no significant difference by Wilcoxon-Mann-Whitney test). The proportion of pulmonary TB cases with positive smear or culture was 63.4% in actively screened patients vs 70.4% in passively detected cases. Among actively screened patients with bacteriological confirmation, 42.2% [CI 27.2-57,2] were asymptomatic compared to 13% [CI 5.31-20.7] for passively screened patients. Considering only smear positive patients, the proportion of symptom-free patients was 22.2% [CI 9.6-34.8] in 45 actively screened cases vs 11-7% [4.4 - 19.0] for 77 passive screening. Cure and treatment completion rate for new cases reached 88% for foreign workers, 83% for asylum seekers, 85% for Swiss patients, 78% for other foreigners. Conclusions: Actively screened patients were more frequently asymptomatic than passively detected cases, even when considering only patients with bacteriological confirmation. The active screening by chest X-ray of an immigrant population with a high prevalence of tuberculosis allows the early detection and treatment of tuberculosis. This may contribute to the protection of the resident population for infection. The outcome of treatment for tuberculosis was satisfactory in all population groups.

Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool.

BACKGROUND: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. METHODOLOGY AND PRINCIPAL FINDINGS: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aβ peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aβ peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. CONCLUSIONS AND SIGNIFICANCE: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.

U.S. National Parks and "The Tragedy of the Commons" : A contribution to the characterization of U.S. mountain guides' professional practice

This paper aims at presenting the stakes related to the access to protected land in the United States and to its conservation, through the analysis of the professional practice of U.S. mountain guides. From a methodological standpoint, this research is based both on a theoretical analysis grounded in the field of environmental economics and on an empirical study. The authors' starting point is Garrett Hardin's paper, "The Tragedy of the Commons" (Science, 1968), even if it introduces some confusion on the notion of common goods. So as to avoid this confusion, the authors use two theoretical tools pertaining to a typology of common goods and the different property rights that can be applied in National Parks. Finally, they apply this framework to the observations made on the field in Colorado in July 2009.

Parametric estimation of pulse arrival time: a robust approach to pulse wave velocity.

Pulse wave velocity (PWV) is a surrogate of arterial stiffness and represents a non-invasive marker of cardiovascular risk. The non-invasive measurement of PWV requires tracking the arrival time of pressure pulses recorded in vivo, commonly referred to as pulse arrival time (PAT). In the state of the art, PAT is estimated by identifying a characteristic point of the pressure pulse waveform. This paper demonstrates that for ambulatory scenarios, where signal-to-noise ratios are below 10 dB, the performance in terms of repeatability of PAT measurements through characteristic points identification degrades drastically. Hence, we introduce a novel family of PAT estimators based on the parametric modeling of the anacrotic phase of a pressure pulse. In particular, we propose a parametric PAT estimator (TANH) that depicts high correlation with the Complior(R) characteristic point D1 (CC = 0.99), increases noise robustness and reduces by a five-fold factor the number of heartbeats required to obtain reliable PAT measurements.

Passive lipoidal diffusion and carrier-mediated cell uptake are both important mechanisms of membrane permeation in drug disposition.

Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development.

Chest physiotherapy using passive expiratory techniques does not reduce bronchiolitis severity: a randomised controlled trial.

Chest physiotherapy (CP) using passive expiratory manoeuvres is widely used in Western Europe for the treatment of bronchiolitis, despite lacking evidence for its efficacy. We undertook an open randomised trial to evaluate the effectiveness of CP in infants hospitalised for bronchiolitis by comparing the time to clinical stability, the daily improvement of a severity score and the occurrence of complications between patients with and without CP. Children <1 year admitted for bronchiolitis in a tertiary hospital during two consecutive respiratory syncytial virus seasons were randomised to group 1 with CP (prolonged slow expiratory technique, slow accelerated expiratory flow, rarely induced cough) or group 2 without CP. All children received standard care (rhinopharyngeal suctioning, minimal handling, oxygen for saturation ≥92%, fractionated meals). Ninety-nine eligible children (mean age, 3.9 months), 50 in group 1 and 49 in group 2, with similar baseline variables and clinical severity at admission. Time to clinical stability, assessed as primary outcome, was similar for both groups (2.9 ± 2.1 vs. 3.2 ± 2.8 days, P = 0.45). The rate of improvement of a clinical and respiratory score, defined as secondary outcome, only showed a slightly faster improvement of the respiratory score in the intervention group when including stethoacoustic properties (P = 0.044). Complications were rare but occurred more frequently, although not significantly (P = 0.21), in the control arm. In conclusion, this study shows the absence of effectiveness of CP using passive expiratory techniques in infants hospitalised for bronchiolitis. It seems justified to recommend against the routine use of CP in these patients.

Constraints on the permeability structure of alluvial aquifers from P-wave sonic logs

Modern sonic logging tools designed for shallow environmental and engineering applications allow for P-wave phase velocity measurements over a wide frequency band. Methodological considerations indicate that, for saturated unconsolidated sediments in the silt to sand range and source frequencies ranging from approximately 1 to 30 kHz, the observable poro-elastic P-wave velocity dispersion is sufficiently pronounced to allow for reliable first-order estimations of the underlying permeability structure. These predictions have been tested on and verified for a surficial alluvial aquifer. Our results indicate that, even without any further calibration, the thus obtained permeability estimates as well as their variabilities within the pertinent lithological units are remarkably close to those expected based on the corresponding granulometric characteristics.

Stoneley wave modeling in heterogeneous porous media with viscous pore fluids

We implemented Biot-type porous wave equations in a pseudo-spectral numerical modeling algorithm for the simulation of Stoneley waves in porous media. Fourier and Chebyshev methods are used to compute the spatial derivatives along the horizontal and vertical directions, respectively. To prevent from overly short time steps due to the small grid spacing at the top and bottom of the model as a consequence of the Chebyshev operator, the mesh is stretched in the vertical direction. As a large benefit, the Chebyshev operator allows for an explicit treatment of interfaces. Boundary conditions can be implemented with a characteristics approach. The characteristic variables are evaluated at zero viscosity. We use this approach to model seismic wave propagation at the interface between a fluid and a porous medium. Each medium is represented by a different mesh and the two meshes are connected through the above described characteristics domain-decomposition method. We show an experiment for sealed pore boundary conditions, where we first compare the numerical solution to an analytical solution. We then show the influence of heterogeneity and viscosity of the pore fluid on the propagation of the Stoneley wave and surface waves in general.