NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality.

PURPOSE: NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. METHODS: Phase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. RESULTS: Patients (median age 54years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. CONCLUSIONS: This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss HIV cohort study.

BACKGROUND: Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement"). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons. METHODS: Self-reported information on sexual preference, sexual partners, and condom use was collected at semi-annual visits in all participants of the prospective Swiss HIV Cohort Study from April 2007 through March 2009. Multivariable logistic regression models were fit using generalized estimating equations to investigate associations between characteristics of cohort participants and condom use. FINDINGS: A total of 7309 participants contributed to 21,978 visits. A total of 4291 persons (80%) reported sexual contacts with stable partners, 1646 (30%) with occasional partners, and 557 (10%) with stable and occasional partners. Of the study participants, 5838 (79.9%) of 7309 were receiving antiretroviral therapy, and of these, 4816 patients (82%) had a suppressed viral load. Condom use varied widely and differed by type of partner (visits with stable partners, 10,368 [80%] of 12,983; visits with occasional partners, 4300 [88%] of 4880) and by serostatus of stable partner (visits with HIV-negative partners, 7105 [89%] of 8174; visits with HIV-positive partners, 1453 [48%] of 2999). Participants were more likely to report unprotected sex with stable partners if they were receiving antiretroviral therapy, if HIV replication was suppressed, and after the publication of the "Swiss statement." Noninjection drug use and moderate or severe alcohol use were associated with unprotected sex. CONCLUSIONS: Antiretroviral treatment and plasma HIV RNA titers influence sexual behavior of HIV-positive persons. Noninjection illicit drug and alcohol use are important risk factors for unprotected sexual contacts.

Evolution, maintenance and ecological consequences of genetic caste determination in " Pogonomyrmex " harvester ants

Summary Division of labor between reproducers (queens) and helpers (workers) is the main characteristic of social insect societies and at the root of their ecological success. Kin selection models predict that phenotypic differences between queens and workers should result from environmental rather than from genetic differences. However, genetic effects on queen and worker differentiation were found in two populations-of Pogonomyrmex harvester ants. Each of the two populations is composed of two genetically distinct lineages. Queens (which can be of either lineage) generally mate with males of their own and of the alternate lineage and produce two types of female offspring, those fertilized by males of the queens' lineage which develop into queens and those fertilized by males of the alternate lineage which develop into workers. All four lineages were further suggested to be themselves of hybrid origin between-the species P: barbatus and P. rugosus, in which queens and workers do not differ genetically. In a first set of experiments, we tested if female caste determination (the differentiation into queens and workers) in the lineages was genetically hardwired and if it was associated with costs in terms of the ability to optimally allocate resources to the production of queens and workers. To this end we first mated queens of-two lineages to a single male. Queens mated to a male of the alternate lineage successfully raised worker offspring whereas queens mated to a male of their own lineage almost always failed to produce workers. This reveals that pure-lineage individuals have lost the ability to develop into workers. Second, we analyzed offspring produced by naturally mated queens. During the stage of colony founding when only workers are produced, naturally mated queens laid a high proportion of pure-lineage eggs but the large majority of these eggs failed to develop. As a consequence, the number of offspring produced by incipient colonies decreased linearly with the proportion of pure-lineage eggs laid by queens. Moreover, queens of the lineage most commonly represented in a given population produced more pure-lineage eggs, in line with the view that they mate randomly with the two types of males and indiscriminately use their sperm. Altogether these results predict frequency-dependent founding success for pairs of lineages because queens of the more common lineage will produce more pure-lineage eggs and their colonies be less successful during the stage of colony founding. To describe the distribution of populations characterized with genetic caste determination relative to the populations with environmental caste determination we genotyped queens and workers collected during a large survey of -additional populations. Genetic caste determination associated with pairs of interbreeding lineages was frequent and widespread in the studied range and we identified four additional lineages displaying genetic caste determination. Overall, there were thus eight highly differentiated lineages with genetic caste determination. These lineages always co-occurred in the same complementary lineage pairs. Three of the four lineage pairs appeared to have a common origin, while their relationship with the forth could not be resolved. The genetic survey also revealed that, in addition to being genetically isolated from one another, all eight lineages were genetically distinct from P. rugosus and P. barbatus, even when colonies of interbreeding lineages co-occurred with colonies of either putative parent at the same site. This raised the question of the mechanisms involved in the reproductive isolation between the lineages and the parental species and between the two lineages of a lineage pair. At a site where one lineage pair co-occurred with P. rugosus, we identified two pre-zygotic mechanisms (differences in timing for mating flights between P. rugosus and the lineage pair and assortative mating) and one post-zygotic mechanism (high levels of hybrid unviablility) which in combination may largely account for the reproductive isolation between the lineages and their parental species. The mechanisms accounting for the reproductive isolation between the two lineages of a lineage pair varied across lineage pairs. In one lineage pair, inter-lineage individuals exclusively occurred in the sterile worker caste, raising the possibility that inter-lineage eggs have completely lost the ability to develop into queens in this lineage pair and that there is thus no opportunity for gene flow. In each of the three remaining lineage pairs, inter-lineage queens were produced by a minority of colonies. In these lineage pairs, colonies headed by inter-lineage queens failed to grow sufficiently to produce reproductive individuals which may account for the reproductive isolation between co-occurring lineages in three lineage pairs. In conclusion, the results of this thesis show that genetic caste determination is costly but widespread in Pogonomyrmex harvester ants. Reproductive isolation among the lineages and between the lineages and the parental species as well as frequency-dependent founding success for co-occurring lineages may contribute to the persistence of this extraordinary system. Résumé La division du travail entre individus reproducteurs (les reines) et individus non-reproducteurs (ouvrières) représente la caractéristique principale des sociétés d'insectes et est à la base de leur succès écologique. Des modèles de sélection de parentèle prédisent que les différences phénotypiques entre reines et ouvrières devraient provenir d'effets environnementaux plutôt que de différences génétiques. Malgré ce fait, des effets génétiques sur la différentiation entre reines et ouvrières ont été montrés dans deux populations de fourmis moissonneuses du genre Pogonomyrmex. Chacune des deux populations est composée de deux lignées génétiquement distinctes. Les reines de chaque lignée s'accouplent en général avec des mâles de leur propre lignée ainsi qu'avec des mâles de l'autre lignée et produisent deux types d'oeufs, ceux qui sont fécondés par les mâles de leur propre lignée qui se développent en nouvelles reines et ceux qui sont fécondés par les mâles de l'autre lignée qui se développent en ouvrières. Il a été suggéré que les lignées sont elles-mêmes des hybrides entre les deux espèces P. barbatus et P. rugosus. Dans ces deux espèces, les reines et ouvrières ne sont pas génétiquement distinctes. Dans une première série d'expériences, nous avons testé si la détermination de la caste femelle (le développement en reine ou en ouvrière) est génétiquement rigide et si elle est associée à des coûts en terme de capacité à allouer de façon optimale les ressources pour la production de reines et d'ouvrières. Pour cela nous avons accouplé des reines de deux lignées avec un seul mâle. Les reines accouplées avec un mâle de l'autre lignée ont élevé de nouvelles ouvrières avec succès alors que les reines accouplées avec un mâle de leur propre lignée ont presque toujours échoué à produire des ouvrières. Ceci montre que les individus de lignée pure ont perdu la capacité de se développer en ouvrière. Deuxièmement, nous avons analysé la descendance de reines qui se sont accouplées naturellement. Durant le stade de fondation de la colonie, où seules des ouvrières sont élevées, les reines accouplées naturellement ont pondu une grande proportion d'oeufs de lignée pure mais la majorité de ces derniers ne se sont pas développés. En conséquence, le nombre de descendants produits par des colonies fondatrices diminuait linéairement avec la proportion des oeufs de lignée pure pondus par la reine en accord avec l'hypothèse que les reines s'accouplent au hasard avec les deux types de mâles et utilisent leur sperme aléatoirement. Dans l'ensemble; ces résultats prédisent un succès de fondation fréquence-dépendant pour les deux lignées, car les reines de la lignée la plus fréquente produiront .plus d'oeufs de lignée pure et leurs colonies auront moins de succès lors de la fondation de colonies par rapport aux colonies de la lignée la moins fréquente. Pour décrire la distribution des-populations caractérisées par une détermination génétique des castes par rapport aux populations caractérisées par une détermination environnementale des castes, nous avons génotypé des reines et des ouvrières qui ont été collectées lors d'une analyse de populations supplémentaires. La détermination génétique des castes associée à des croisements entre lignées est fréquente et largement répartie dans l'aire étudiée. Nous avons identifié quatre lignées supplémentaires, ayant une détermination génétique des castes, pour un total de huit lignées. Ces huit lignées forment quatre paires de lignées et on ne trouve jamais deux lignées de paires différentes, dans une population. Trois des quatre paires de lignées s'avèrent avoir une origine commune alors que leur relation avec la quatrième paire de lignées n'a pas pu être résolue. L'analyse génétique de populations supplémentaires a également révélé qu'en plus d'être génétiquement isolées les unes des autres, les huit lignées sont génétiquement distinctes de P. rugosus et P. barbatus même si les colonies d'une paire de lignées se trouvent en sympatrie avec l'une ou l'autre des espèces parentales. Ceci relève la question des mécanismes impliqués dans l'isolation reproductive entre les lignées et les espèces parentales ainsi qu'entre les deux lignées d'une paire. En étudiant un site où une paire de lignées se trouve en sympatrie avec P. rugosus, nous avons identifié deux mécanismes pré-zygotiques (des différences dans le timing du vol nuptial entre P. rugosus et les lignées et des accouplements assortis) ainsi qu'un mécanisme post-zygotique (un niveau élevé de non-viabilité des hybrides). En combinaison, ces mécanismes peuvent largement expliquer l'isolement reproductif entre les lignées et leurs espèces parentales. Les mécanismes contribuant à l'isolement reproductif entre les deux lignées d'une paire variaient entre paires de lignées. Dans une paire, les individus de génotype inter-lignée se trouvent uniquement dans la caste stérile des ouvrières, suggérant qu'il n'y a pas d'opportunité pour avoir du flux de gènes entre les deux lignées ce cette paire. Dans chacune des trois autres paires de lignées des nouvelles reines de génotype inter-lignée sont produites par une minorité de colonies. Par contre, les colonies avec une reine mère de génotype inter-lignée ne se développent pas suffisamment pour produire des individus reproducteurs. Ceci peut donc expliquer pourquoi il n'y a pas de flux de gènes entre les deux lignées de trois paires. En conclusion, les résultats de cette thèse montrent que la détermination génétique de la caste est coûteuse mais très répandue chez les fourmis. moissonneuses du genre Pogonomyrmex. L'isolement reproductif des lignées entre elles et avec les espèces parentales, ainsi qu'un succès de fondation fréquence-dépendant contribuent à la persistance de ce système extraordinaire.

Frequency-dependent sexual selection with respect to offspring fitness returns is consistent with predictions from rock-paper-scissors dynamics in the European common lizard

Genetic polymorphism can be maintained over time by negative frequency-dependent (FD) selection induced by Rock-paper-scissors (RPS) social systems. RPS games produce cyclic dynamics, and have been suggested to exist in lizards, insects, isopods, plants, and bacteria. Sexual selection is predicted to accentuate the survival of the future progeny during negative FD survival selection. More specifically, females are predicted to select mates that produce progeny genotypes that exhibit highest survival during survival selection imposed by adult males. However, no empirical evidence demonstrates the existence of FD sexual selection with respect to fitness payoffs of genetic polymorphisms. Here we tested this prediction using the common lizard Zootoca vivipara, a species with three male color morphs (orange, white, yellow) that exhibit morph frequency cycles. In a first step we tested the congruence of the morph frequency change with the predicted change in three independent populations, differing in male color morph frequency and state of the FD morph cycle. Thereafter we ran standardized sexual selection assays in which we excluded alternative mechanisms that potentially induce negative FD selection, and we quantified inter-sexual behavior. The patterns of sexual selection and the observed behavior were in line with context-dependent female mate choice and male behavior played a minor role. Moreover, the strength of the sexual selection was within the magnitude of selection required to produce the observed 3-4-year and 6-8 year morph frequency cycles at low and high altitudes, respectively. In summary, the study provides the first experimental evidence that underpins the crucial assumption of the RPS games suggested to exist in lizards, insects, isopods, and plants; namely, that sexual selection produces negative-FD selection. This indicates that sexual selection, in our study exert by females, might be a crucial driver of the maintenance of genetic polymorphisms.

Orthogonal higher order structure and confirmatory factor analysis of the French Wechsler Adult Intelligence Scale (WAIS-III).

According to the most widely accepted Cattell-Horn-Carroll (CHC) model of intelligence measurement, each subtest score of the Wechsler Intelligence Scale for Adults (3rd ed.; WAIS-III) should reflect both 1st- and 2nd-order factors (i.e., 4 or 5 broad abilities and 1 general factor). To disentangle the contribution of each factor, we applied a Schmid-Leiman orthogonalization transformation (SLT) to the standardization data published in the French technical manual for the WAIS-III. Results showed that the general factor accounted for 63% of the common variance and that the specific contributions of the 1st-order factors were weak (4.7%-15.9%). We also addressed this issue by using confirmatory factor analysis. Results indicated that the bifactor model (with 1st-order group and general factors) better fit the data than did the traditional higher order structure. Models based on the CHC framework were also tested. Results indicated that a higher order CHC model showed a better fit than did the classical 4-factor model; however, the WAIS bifactor structure was the most adequate. We recommend that users do not discount the Full Scale IQ when interpreting the index scores of the WAIS-III because the general factor accounts for the bulk of the common variance in the French WAIS-III. The 4 index scores cannot be considered to reflect only broad ability because they include a strong contribution of the general factor.

Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort.

OBJECTIVES: Data on the frequency of extraintestinal manifestations (EIMs) in Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk factors are scarce. We evaluated their prevalence and risk factors in a large nationwide cohort of inflammatory bowel disease (IBD) patients. METHODS: IBD patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study) were prospectively included. Data from validated physician enrolment questionnaires were analyzed. RESULTS: A total of 950 patients were included, 580 (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple logistic regression identified the following risk factors for ongoing EIM in CD: active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23, P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No risk factors were identified in UC patients. CONCLUSIONS: EIMs are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitating their diagnosis and therapeutic management.

Use of combined suspension laryngoscopy, flexible bronchoscopy and high frequency jet ventilation for Y-shaped airway stents delivery

La trachée et les bronches proximales sont de fins conduits subtils, ingénieusement structurés par une partie cartilagineuse antérieure résistante aux variations de pression et une partie membraneuse postérieure souple. Par leurs faibles volumes (espace mort) ils délivrent un grand pourcentage de l'air inspiré aux voies distales, puis au parenchyme pulmonaire, permettant les échanges de gaz. Cette belle harmonie respiratoire peut être rapidement mise à mal dès qu'un processus atteint ces voies respiratoires proximales, soit en les comprimant, processus sténosant, soit en affaiblissant leur structure, trachéo-bronchomalacie, soit en ouvrant leur paroi sur les structures médiastinales, fistule trachéo/broncho-médiastinales, pleurales ou autres. Le pronostic vital est alors rapidement engagé au vu de l'absolue nécessité du bon fonctionnement de ces fins conduits, une petite diminution du calibre de leurs fines lumières provoquant une baisse importante de leurs surfaces. Dans ces situations à haut potentiel de complication majeure les interventions endoscopiques pour restaurer l'intégrité de ces conduits sont alors fort risquées, et il est primordial de pouvoir les effectuer dans un cadre sécurisé au maximum. La réalisation de ces gestes par la technique décrite dans notre article « Use of combined suspension laryngoscopy, flexible bronchoscopy and high frequency jet ventilation forY-shaped airway stents delivery" permet la sécurité nécessaire à ces situations instable, en effet -la laryngoscopie en suspension expose les voies proximales en offrant un accès le plus large possible à l'arbre trachéobronchique ce qui permet l insertion de multiples instruments parfois volumineux, -la Jet ventilation assure une oxygénation et une ventilation adéquate par un fin cathéter placé soit dans le poumon sain, soit en distalité de la lésion -la bronchoscopie souple, passant au travers d'endroits exigus et courbes permet le déploiement sous vision direct, au millimètre près, de divers dispositifs. Cette association remplace avantageusement la technique traditionnelle qui insère les stents à l'aveugle, et en apnée, ce qui représente de haut risque de mauvais positionnement des stents avec des conséquences immédiates sur l'oxygénation et la ventilation souvent déjà bien altérées. Perspective et conclusion : cette technique est utile pour l'insertion des stents en Y, centraux, comme décrit dans notre article, et les indications peuvent être étendues aux stents distaux pour lesquels l'accès n'est parfois pas aisé avec le bronchoscope rigide, et pour d'autres interventions endoscopiques, laser, cryothérapie, radiofréquence ou l'insertion de nouveaux dispositifs.

Use of neuroenhancement drugs: prevalence, frequency and use expectations in Switzerland

Objective: The present study investigates the use expectations, prevalence and frequency of neuroenhancement drug (ND) use among the Swiss male population, separating college students from others. Methods: Young Swiss men were invited to participate in the Cohort Study on Substance Use Risk Factors. A total of 5,967 participants responded to questions on six types of NDs (wakefulness medication, antidepressants, Alzheimer's disease medication, Parkinson's disease medication, attention deficit-hyperactivity disorder (ADHD) medication, and beta-blockers). The frequency of use depending on five expectations (to enhance wakefulness, attention, memory, concentration and stress reduction) was analyzed for a twelve-month period. Results: (1) About 3% of the sample indicated use of at least one ND; (2) ADHD medication was the most prevalent; (3) The type of ND preferred differed depending on academic status (4). Quantitatively, over the year, college student users used ND much less frequently than other users. Conclusions: Prevalence of ND use is low in Switzerland relative to other countries such as the United States. Patterns of ND use differed depending on academic status, suggesting that while college student ND users tended to do so rarely (probably to enhance cognitive abilities for exams), non-college male users used other NDs more frequently (probably to "get high").

Preliminary regional rockfall hazard mapping using LIDAR-based slope frequency distribution and CONEFALL modeling

A factor limiting preliminary rockfall hazard mapping at regional scale is often the lack of knowledge of potential source areas. Nowadays, high resolution topographic data (LiDAR) can account for realistic landscape details even at large scale. With such fine-scale morphological variability, quantitative geomorphometric analyses become a relevant approach for delineating potential rockfall instabilities. Using digital elevation model (DEM)-based ?slope families? concept over areas of similar lithology and cliffs and screes zones available from the 1:25,000 topographic map, a susceptibility rockfall hazard map was drawn up in the canton of Vaud, Switzerland, in order to provide a relevant hazard overview. Slope surfaces over morphometrically-defined thresholds angles were considered as rockfall source zones. 3D modelling (CONEFALL) was then applied on each of the estimated source zones in order to assess the maximum runout length. Comparison with known events and other rockfall hazard assessments are in good agreement, showing that it is possible to assess rockfall activities over large areas from DEM-based parameters and topographical elements.

Simultaneous B(0)- and B(1)+-map acquisition for fast localized shim, frequency, and RF power determination in the heart at 3 T.

High-field (>or=3 T) cardiac MRI is challenged by inhomogeneities of both the static magnetic field (B(0)) and the transmit radiofrequency field (B(1)+). The inhomogeneous B fields not only demand improved shimming methods but also impede the correct determination of the zero-order terms, i.e., the local resonance frequency f(0) and the radiofrequency power to generate the intended local B(1)+ field. In this work, dual echo time B(0)-map and dual flip angle B(1)+-map acquisition methods are combined to acquire multislice B(0)- and B(1)+-maps simultaneously covering the entire heart in a single breath hold of 18 heartbeats. A previously proposed excitation pulse shape dependent slice profile correction is tested and applied to reduce systematic errors of the multislice B(1)+-map. Localized higher-order shim correction values including the zero-order terms for frequency f(0) and radiofrequency power can be determined based on the acquired B(0)- and B(1)+-maps. This method has been tested in 7 healthy adult human subjects at 3 T and improved the B(0) field homogeneity (standard deviation) from 60 Hz to 35 Hz and the average B(1)+ field from 77% to 100% of the desired B(1)+ field when compared to more commonly used preparation methods.

Orthogonal organic and aqueous-based washes of tissue sections to enhance protein sensitivity by MALDI imaging mass spectrometry.

Imaging mass spectrometry (IMS) is an emergent and innovative approach for measuring the composition, abundance and regioselectivity of molecules within an investigated area of fixed dimension. Although providing unprecedented molecular information compared with conventional MS techniques, enhancement of protein signature by IMS is still necessary and challenging. This paper demonstrates the combination of conventional organic washes with an optimized aqueous-based buffer for tissue section preparation before matrix-assisted laser desorption/ionization (MALDI) IMS of proteins. Based on a 500 mM ammonium formate in water-acetonitrile (9:1; v/v, 0.1% trifluororacetic acid, 0.1% Triton) solution, this buffer wash has shown to significantly enhance protein signature by profiling and IMS (~fourfold) when used after organic washes (70% EtOH followed by 90% EtOH), improving the quality and number of ion images obtained from mouse kidney and a 14-day mouse fetus whole-body tissue sections, while maintaining a similar reproducibility with conventional tissue rinsing. Even if some protein losses were observed, the data mining has demonstrated that it was primarily low abundant signals and that the number of new peaks found is greater with the described procedure. The proposed buffer has thus demonstrated to be of high efficiency for tissue section preparation providing novel and complementary information for direct on-tissue MALDI analysis compared with solely conventional organic rinsing.

Proposition d'un concept de contrôle de gestion pour la division "infrastructure routière" de l'Office fédéral des routes (OFROU)

La présente étude propose une méthodologie aboutissant à la conception d'un système de contrôle de gestion pour la division « infrastructure routière » ou « I » de l'Office fédéral des routes (OFROU). La première partie de ce travail situe l'OFROU dans son contexte de réformes et identifie les raisons qui justifient l'implantation d'un système de contrôle de gestion à l'OFROU. La deuxième partie pose les jalons permettant d'établir un contrôle de gestion dans sa division « I ». Elle cherche d'abord à donner une définition du contrôle de gestion dans le secteur public, puis présente un état des lieux du système de gestion existant. Finalement, les systèmes de contrôle de gestion de deux autres offices GMEB, MétéoSuisse et armasuisse immobilier, sont analysés afin d'en tirer des éléments pertinents pouvant servir à la conception du contrôle de gestion à l'OFROU. La troisième propose un contrôle de gestion pour la division « I ». Le travail montre que la réalisation d'un concept de contrôle de gestion pour la division « I » n'est pas évidente. Cette dernière, qui est en train de se mettre en place, manque encore d'expérience pour identifier clairement les éléments clé à insérer dans le système. On observe un grand embarras entre le stade du savoir et celui du savoir faire concret. La méthodologie et l'analyse présentées dans ce travail pourraient contribuer à développer un savoir faire interne aboutissant rapidement à la mise sur pied d'un système de contrôle de gestion pour la division « I ». Die vorliegende Studie schlägt eine Methodik zur Erarbeitung eines Management-Kontrollsystems für die Abteilung « Strasseninfrastruktur » oder « I » des Bundesamts für Strassen (ASTRA) vor. Der erste Teil dieser Arbeit stellt das ASTRA im Spannungsfeld dieser Reformen. Ihre Konsequenzen lassen die Einführung eines Management-Kontrollsystems im ASTRA folgerichtig erscheinen. Im zweiten Teil geht es darum, Wegmarken zu setzen, die die Einführung einer Managementkontrolle in der Abteilung « I » in die richtigen Bahnen lenken. Es wird versucht, eine Begriffsbestimmung der Managementkontrolle im öffentlichen Sektor sowie eine Bestandesaufnahme der bestehenden Systeme vorzunehmen. Schliesslich werden die Management-Kontrollsysteme zweier anderer FLAG-Ämter, MeteoSchweiz und armasuisse immobilier, auf mögliche Nutzen für den Aufbau der Managementkontrolle des ASTRA analysiert. Der dritte Teil beinhaltet einen Vorschlag, wie die Management-Kontrolle für die Abteilung « I » aussehen könnte. Die Arbeit zeigt, dass die Erarbeitung eines Management-Kontrollkonzepts für die Abteilung « I » keine einfache Aufgabe ist. Es fehlt an Erfahrung, um die Schlüsselbausteine des Systems erkennen zu können. Zwischen dem Stadium des Wissens und dem des konkreten Know-hows klafft ein empfindlicher Graben. Methodik und Analyse, wie sie in der vorliegenden Arbeit beschrieben werden, könnten zum Aufbau eines internen Know-hows beitragen, das die rasche Verwirklichung eines Management-Kontrollsystems für die Abteilung « I » erlauben könnte.

Adaptive filtering methods for identifying cross-frequency couplings in human EEG.

Oscillations have been increasingly recognized as a core property of neural responses that contribute to spontaneous, induced, and evoked activities within and between individual neurons and neural ensembles. They are considered as a prominent mechanism for information processing within and communication between brain areas. More recently, it has been proposed that interactions between periodic components at different frequencies, known as cross-frequency couplings, may support the integration of neuronal oscillations at different temporal and spatial scales. The present study details methods based on an adaptive frequency tracking approach that improve the quantification and statistical analysis of oscillatory components and cross-frequency couplings. This approach allows for time-varying instantaneous frequency, which is particularly important when measuring phase interactions between components. We compared this adaptive approach to traditional band-pass filters in their measurement of phase-amplitude and phase-phase cross-frequency couplings. Evaluations were performed with synthetic signals and EEG data recorded from healthy humans performing an illusory contour discrimination task. First, the synthetic signals in conjunction with Monte Carlo simulations highlighted two desirable features of the proposed algorithm vs. classical filter-bank approaches: resilience to broad-band noise and oscillatory interference. Second, the analyses with real EEG signals revealed statistically more robust effects (i.e. improved sensitivity) when using an adaptive frequency tracking framework, particularly when identifying phase-amplitude couplings. This was further confirmed after generating surrogate signals from the real EEG data. Adaptive frequency tracking appears to improve the measurements of cross-frequency couplings through precise extraction of neuronal oscillations.