Regional consumption of antibiotics : a demand system approach

Through this paper. we have attempted to model the demand for different classes of antibiotics used for respiratory infections in outpatient care in Switzerland using a spatial version of the linear approximate Almost Ideal Demand System (AIDS) model. This model takes spatial dependency into account by means of spatial lags of antibiotic budget shares. We control for the health status of patients and the potential harmful effects of antibiotic use in terms of bacterial resistance. Elasticities to socioeconomic determinants of consumption and own- and cross-price elasticities between different groups of antibiotic have also been computed in this paper. Significant cross-price elasticities are found between newer or more expensive generations and older or less expensive generations of antibiotics. (C) 2009 Elsevier B.V. All rights reserved.

The renin-angiotensin system and arterial wall behavior.

To assess the behavior of the arterial wall in hypertensive patients, we developed a noninvasive ultrasonic device. Simultaneous recordings of internal diameter and blood pressure over the whole cardiac cycle are used to establish compliance-pressure curves. Blood pressure, which is a co-determinant of compliance, is thus taken into account. This method allows one to compare arteries from patients with different blood pressures. Arterial compliance and distensibility were first investigated in healthy young volunteers administered either lisinopril (20 mg), atenolol (100 mg) or nitrendipine (20 mg) once a day. After 8 days of treatment, only lisinopril was found to increase arterial compliance. Subsequently, we compared arterial diameter- and distensibility-pressure curves from newly diagnosed and untreated hypertensive patients with those of matched normotensive control patients. Diameter-pressure curves did not differ significantly between the groups and distensibility was not reduced. Similar findings were later obtained in an animal model, when mechanical properties of carotid arteries were compared between spontaneously hypertensive rats and normotensive counterparts (Wistar-Kyoto rats). These results, although interesting by providing noninvasive information on the elastic response of the wall, call for further development of the technique to be able to measure arterial wall thickness. Stress-strain relationship could ultimately be established to thoroughly characterize physical properties of blood vessel walls.

Influence of the ankle arthropathies on the 3D kinematics of the lower limbs during gait: analysis with an ambulatory system.

Introduction: Ankle arthropathy is associated with a decreased motion of the ankle-hindfoot during ambulation. Ankle arthrodesis was shown to result in degeneration of the neighbour joints of the foot. Inversely, total ankle arthroplasty conceptually preserves the adjacent joints because of the residual mobility of the ankle but this has not been demonstrated yet in vivo. It has also been reported that degenerative ankle diseases, and even arthrodesis, do not result in alteration of the knee and hip joints. We present the preliminary results of a new approach of this problem based on ambulatory gait analysis. Patients and Methods: Motion analysis of the lower limbs was performed using a Physilog® (BioAGM, CH) system consisting of three-dimensional (3D) accelerometer and gyroscope, coupled to a magnetic system (Liberty©, Polhemus, USA). Both systems have been validated. Three groups of two patients were included into this pilot study and compared to healthy subjects (controls) during level walking: patients with ankle osteoarthritis (group 1), patients treated by ankle arthrodesis (group 2), patients treated by total ankle prosthesis (group 3). Results: Motion patterns of all analyzed joints over more than 20 gait cycles in each subject were highly repeatable. Motion amplitude of the ankle-hindfoot in control patients was similar to recently reported results. Ankle arthrodesis limited the motion of the ankle-hindfoot in the sagittal and horizontal planes. The prosthetic ankle allowed a more physiologic movement in the sagittal plane only. Ankle arthritis and its treatments did not influence the range of motion of the knee and hip joint during stance phase, excepted for a slight decrease of the hip flexion in groups 1 and 2. Conclusion: The reliability of the system was shown by the repeatability of the consecutive measurements. The results of this preliminary study were similar to those obtained through laboratory gait analysis. However, our system has the advantage to allow ambulatory analysis of 3D kinematics of the lower limbs outside of a gait laboratory and in real life conditions. To our knowledge this is a new concept in the analysis of ankle arthropathy and its treatments. Therefore, there is a potential to address specific questions like the difficult comparison of the benefits of ankle arthroplasty versus arthrodesis. The encouraging results of this pilot study offer the perspective to analyze the consequences of ankle arthropathy and its treatments on the biomechanics of the lower limbs ambulatory, in vivo and in daily life conditions.

Cerebrospinal fluid biomarkers of central nervous system dysfunction in HIV-infected patients

Background :¦In addition to opportunistic infections of the central nervous system (CNS), which are due to immunosuppression related to HIV, the latter virus, itself, can cause neuropathological abnormalities which are located mainly in the basal ganglia and are characterized by microglial giant cells, reactive astrocytosis and perivascular monocytes. This HIV encephalopathy is characterized, clinically, by psycho-motor slowing, memory loss, difficulties in complex tasks requiring executive functions, as well as motor disorders .These cognitive deficits are grouped under the acronym of HIV-associated neurocognitive disorders (HAND). In fact, HANDs are subdivided in three groups in accordance with the severity of the cognitive impairment: Asymptomatic Neurocognitive Impairment (ANI), Mild/moderate Neurocognitive Disorders (MND) and HIV Associated Dementia (HAD).¦While the incidence of HAD has significantly decreased in the era of combined antiretrobiral therapy (cART), the prevalence of milder forms of HIV-associated neurocognitive disorders HAND seem to have increased. There are many potential reasons to explain this state of facts.¦An important question is to understand how soon the brain may be affected by HIV. Since performing a biopsy in these patients is not an issue, the study of the CSF represents the best available way to look at putative biomarkers of inflammation/neurodegeneration in the CNS. Here, we wanted to examined the putative usefulness of different biomarkers as early indicators of anti-retroviral failure at the level of the CNS. We chose to study the CSF levels of:¦Amyloid-β 1-42 (Aβ42), Tau total (tTau), phosphorylated Tau (pTau), Neopterin and S100-β.¦Indeed, these molecules are representative biomarkers of the major cells of the CNS, i.e. neurons,¦macrophages/microglia and astrocytes.¦To examine how sensitive were these CSF biomarkers to indicate CNS insults caused by HIV, we proposed to take advantage of the MOST (Monotherapy Switzerland/Thailand study) study, recently published in AIDS. Thus, we collaborated with Prof. Pietro Vernazza in St-Gall. In MOST study, monotherapy (MT) consisting in ritonavir-boosted lopinavir (LPV/r) was compared to continuous conventional antiretroviral therapy including several molecules, hereafter referred as CT¦Methods :We tested 61 cerebrospinal fluid (CSF) samples from 52 patients enrolled in MOST, including 34 CSF samples of CT and 27 of MT (mean duration on MT: 47+20 weeks) in patients who maintained full VL suppression in blood (<50cps/ml). Using enzyme-linked immunosorbent assay (ELISA), we determined the CSF concentration of S100-beta (astrocytosis), neopterin (microglia, inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-beta 1-42 (Abeta), the latter three markers indicating neuronal damages. The CSF samples of 37 HIV-negative patients with Alzheimer dementia (AD) served as controls. Results are expressed in pg/ml and reported as median ± interquartile range. Mann Whitney-U test was used to compare the results of a given biomarker between two groups and the Fisher test to compare frequencies.¦Results: We found a higher concentration of S100-beta (570±1132) and neopterin (2.5±2.9) in the CSF of MT versus CT (0±532, p=0.002 and 1.2±2.5, p=0.058, respectively). A cutoff of 940 pg/ml for S100-beta allowed to discriminate MT (11 above versus 16 below) from CT (1 vs 33, p=0.0003). At a lesser extent, a cutoff of 11 pg/ml for neopterin separated MT (4 above versus 23) from CT (0 vs 34, p=0.034) (Figure).¦In AD, tTau was higher (270±414) and Abeta lower (234±328) than in CT (150±153, p=0.0078, and 466±489, p=0.007, respectively). Such as for CT, Abeta was lower in AD than in MT (390±412, p=0.01). However, contrasting with CT, the levels of tTau were not different between AD and MT (199±177, p=0.11). S100b (173±214; p=0.0006) and neopterin (1.1±0.9; p=0.0014) were lower in AD than MT.¦Conclusions: Despite full VL-suppression in blood, HIV monotherapy is sufficient to trigger inflammation and, especially, astrocytosis. CSF markers of patients on CT have the same profile as reported for healthy subjects, suggesting that CT permits a good control of HIV in the brain. Finally, the levels of tTau, which are relatively similar between AD and MT patients, suggest that neurons are damaged during monotherapy.

Insulin and NPY pathways and the control of GnRH function and puberty onset.

Energy balance exerts a critical influence on reproductive function. Leptin and insulin are among the metabolic factors signaling the nutritional status of an individual to the hypothalamus, and their role in the overall modulation of the activity of GnRH neurons is increasingly recognized. As such, they participate to a more generalized phenomenon: the signaling of peripheral metabolic changes to the central nervous system. The physiological importance that the interactions occurring between peripheral metabolic factors and the central nervous system bear for the control of food intake is increasingly recognized. The central mechanisms implicated are the focus of attention of very many research groups worldwide. We review here the experimental data that suggest that similar mechanisms are at play for the metabolic control of the neuroendocrine reproductive function. It is appearing that metabolic signals are integrated at the levels of first-order neurons equipped with the proper receptors, ant that these neurons send their signals towards hypothalamic GnRH neurons which constitute the integrative element of this network.

Chlamydia control activities in Europe: cross-sectional survey.

BACKGROUND: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. METHODS: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. RESULTS: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). CONCLUSION: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.

Horizontal, but not vertical, biotic interactions affect fine-scale plant distribution patterns in a low-energy system

Studies of species range determinants have traditionally focused on abiotic variables (typically climatic conditions), and therefore the recent explicit consideration of biotic interactions represents an important advance in the field. While these studies clearly support the role of biotic interactions in shaping species distributions, most examine only the influence of a single species and/or a single interaction, failing to account for species being subject to multiple concurrent interactions. By fitting species distribution models (SDMs), we examine the influence of multiple vertical (i.e., grazing, trampling, and manuring by mammalian herbivores) and horizontal (i.e., competition and facilitation; estimated from the cover of dominant plant species) interspecific interactions on the occurrence and cover of 41 alpine tundra plant species. Adding plant-plant interactions to baseline SDMs (using five field-quantified abiotic variables) significantly improved models' predictive power for independent data, while herbivore-related variables had only a weak influence. Overall, abiotic variables had the strongest individual contributions to the distribution of alpine tundra plants, with the importance of horizontal interaction variables exceeding that of vertical interaction variables. These results were consistent across three modeling techniques, for both species occurrence and cover, demonstrating the pattern to be robust. Thus, the explicit consideration of multiple biotic interactions reveals that plant-plant interactions exert control over the fine-scale distribution of vascular species that is comparable to abiotic drivers and considerably stronger than herbivores in this low-energy system.

Between-year variation in population sex ratio increases with complexity of the breeding system in Hymenoptera.

While adaptive adjustment of sex ratio in the function of colony kin structure and food availability commonly occurs in social Hymenoptera, long-term studies have revealed substantial unexplained between-year variation in sex ratio at the population level. In order to identify factors that contribute to increased between-year variation in population sex ratio, we conducted a comparative analysis across 47 Hymenoptera species differing in their breeding system. We found that between-year variation in population sex ratio steadily increased as one moved from solitary species, to primitively eusocial species, to single-queen eusocial species, to multiple-queen eusocial species. Specifically, between-year variation in population sex ratio was low (6.6% of total possible variation) in solitary species, which is consistent with the view that in solitary species, sex ratio can vary only in response to fluctuations in ecological factors such as food availability. In contrast, we found significantly higher (19.5%) between-year variation in population sex ratio in multiple-queen eusocial species, which supports the view that in these species, sex ratio can also fluctuate in response to temporal changes in social factors such as queen number and queen-worker control over sex ratio, as well as factors influencing caste determination. The simultaneous adjustment of sex ratio in response to temporal fluctuations in ecological and social factors seems to preclude the existence of a single sex ratio optimum. The absence of such an optimum may reflect an additional cost associated with the evolution of complex breeding systems in Hymenoptera societies.

Swiss behavioural surveillance system 1986-2008

Background: Second generation surveillance is a central feature of HIV/AIDS policy in Switzerland. Behavioural surveys in the general population, men having sex with men (MSM) and injecting drug users (IDU) have been regularly conducted since the early nineties. After peaking at 2144 cases in 1991, the number of new HIV cases notified to the Ministry of Health decreased in each subpopulation until 2000 (n=578) and then rose again to 735 in 2006. The recent increase is mainly due to MSM. Methods: In the general population, representative cross-sectional telephone surveys have been conducted 11 times since 1987. Surveys in convenience samples of MSM, recruited through gay newspapers and gay organisations, have been conducted 5 times since 1992. Surveys among IDU's attending needle exchange programmes have been conducted 5 times since 1993. Condom statistics, available since 1986, are included in the behavioural surveillance system. Results: In the general population aged 17-30, systematic condom use with casual partners in the last six months increased from 8.0% in 1987 to 75.8% in 2007. The proportion of MSM reporting anal intercourse with casual partners in the last 12 months increased from 61% in 1992 to 79% in 2007 (lowest value 56% in 1994) and unprotected anal intercourse with these partners increased from 14 % in 1992 to 24% in 2007 (lowest value 9% in 1994). The proportion of IDUs reporting borrowing used injection equipment decreased from 16.5% in 1993 to 8.9% in 2006. The ratio condoms released to retail/population aged 15-65 increased from 1.68 in 1986 to 3.8 in 2006. Conclusions: It has been possible to maintain a coherent behavioural surveillance system on a long-term basis, allowing for the monitoring of HIV prevention policy outcome and forseeing the development and distribution of new HIV cases in the population.

Shoulder sensorimotor control assessment by force platform: feasibility and reliability.

Given the important role of the shoulder sensorimotor system in shoulder stability, its assessment appears of interest. Force platform monitoring of centre of pressure (CoP) in upper-limb weight-bearing positions is of interest as it allows integration of all aspects of shoulder sensorimotor control. This study aimed to determine the feasibility and reliability of shoulder sensorimotor control assessment by force platform. Forty-five healthy subjects performed two sessions of CoP measurement using Win-Posturo(®) Medicapteurs force platform in an upper-limb weight-bearing position with the lower limbs resting on a table to either the anterior superior iliac spines (P1) or upper patellar poles (P2). Four different conditions were tested in each position in random order: eyes open or eyes closed with trunk supported by both hands and eyes open with trunk supported on the dominant or non-dominant side. P1 reliability values were globally moderate to high for CoP length, CoP velocity and CoP standard deviation (SD), standard error of measurement ranged from 6·0% to 26·5%, except for CoP area. P2 reliability values were globally low and not clinically acceptable. Our results suggest that shoulder sensorimotor control assessment by force platform is feasible and has good reliability in upper-limb weight-bearing positions when the lower limbs are resting on a table to the anterior superior iliac spines. CoP length, CoP velocity and CoP SD velocity appear to be the most reliable variables.

Global GacA-steered control of cyanide and exoprotease production in Pseudomonas fluorescens involves specific ribosome binding sites.

The conserved two-component regulatory system GacS/GacA determines the expression of extracellular products and virulence factors in a variety of Gram-negative bacteria. In the biocontrol strain CHA0 of Pseudomonas fluorescens, the response regulator GacA is essential for the synthesis of extracellular protease (AprA) and secondary metabolites including hydrogen cyanide. GacA was found to exert its control on the hydrogen cyanide biosynthetic genes (hcnABC) and on the aprA gene indirectly via a posttranscriptional mechanism. Expression of a translational hcnA'-'lacZ fusion was GacA-dependent whereas a transcriptional hcnA-lacZ fusion was not. A distinct recognition site overlapping with the ribosome binding site appears to be primordial for GacA-steered regulation. GacA-dependence could be conferred to the Escherichia coli lacZ mRNA by a 3-bp substitution in the ribosome binding site. The gene coding for the global translational repressor RsmA of P. fluorescens was cloned. RsmA overexpression mimicked partial loss of GacA function and involved the same recognition site, suggesting that RsmA is a downstream regulatory element of the GacA control cascade. Mutational inactivation of the chromosomal rsmA gene partially suppressed a gacS defect. Thus, a central, GacA-dependent switch from primary to secondary metabolism may operate at the level of translation.

Social and medical vulnerability factors of emergency department frequent users in a universal health insurance system.

OBJECTIVES: The objectives were to identify the social and medical factors associated with emergency department (ED) frequent use and to determine if frequent users were more likely to have a combination of these factors in a universal health insurance system. METHODS: This was a retrospective chart review case-control study comparing randomized samples of frequent users and nonfrequent users at the Lausanne University Hospital, Switzerland. The authors defined frequent users as patients with four or more ED visits within the previous 12 months. Adult patients who visited the ED between April 2008 and March 2009 (study period) were included, and patients leaving the ED without medical discharge were excluded. For each patient, the first ED electronic record within the study period was considered for data extraction. Along with basic demographics, variables of interest included social (employment or housing status) and medical (ED primary diagnosis) characteristics. Significant social and medical factors were used to construct a logistic regression model, to determine factors associated with frequent ED use. In addition, comparison of the combination of social and medical factors was examined. RESULTS: A total of 359 of 1,591 frequent and 360 of 34,263 nonfrequent users were selected. Frequent users accounted for less than a 20th of all ED patients (4.4%), but for 12.1% of all visits (5,813 of 48,117), with a maximum of 73 ED visits. No difference in terms of age or sex occurred, but more frequent users had a nationality other than Swiss or European (n = 117 [32.6%] vs. n = 83 [23.1%], p = 0.003). Adjusted multivariate analysis showed that social and specific medical vulnerability factors most increased the risk of frequent ED use: being under guardianship (adjusted odds ratio [OR] = 15.8; 95% confidence interval [CI] = 1.7 to 147.3), living closer to the ED (adjusted OR = 4.6; 95% CI = 2.8 to 7.6), being uninsured (adjusted OR = 2.5; 95% CI = 1.1 to 5.8), being unemployed or dependent on government welfare (adjusted OR = 2.1; 95% CI = 1.3 to 3.4), the number of psychiatric hospitalizations (adjusted OR = 4.6; 95% CI = 1.5 to 14.1), and the use of five or more clinical departments over 12 months (adjusted OR = 4.5; 95% CI = 2.5 to 8.1). Having two of four social factors increased the odds of frequent ED use (adjusted = OR 5.4; 95% CI = 2.9 to 9.9), and similar results were found for medical factors (adjusted OR = 7.9; 95% CI = 4.6 to 13.4). A combination of social and medical factors was markedly associated with ED frequent use, as frequent users were 10 times more likely to have three of them (on a total of eight factors; 95% CI = 5.1 to 19.6). CONCLUSIONS: Frequent users accounted for a moderate proportion of visits at the Lausanne ED. Social and medical vulnerability factors were associated with frequent ED use. In addition, frequent users were more likely to have both social and medical vulnerabilities than were other patients. Case management strategies might address the vulnerability factors of frequent users to prevent inequities in health care and related costs.

Determination of Vasopressin and Desmopressin in urine by means of liquid chromatography coupled to quadrupole time-of-flight mass spectrometry for doping control purposes.

The anti-diuretic neurohypophysial hormone Vasopressin (Vp) and its synthetic analogue Desmopressin (Dp, 1-desamino-vasopressin) have received considerable attention from doping control authorities due to their impact on physiological blood parameters. Accordingly, the illicit use of Desmopressin in elite sport is sanctioned by the World Anti-Doping Agency (WADA) and the drug is classified as masking agent. Vp and Dp are small (8-9 amino acids) peptides administered orally as well as intranasally. Within the present study a method to determine Dp and Vp in urinary doping control samples by means of liquid chromatography coupled to quadrupole high resolution time-of-flight mass spectrometry was developed. After addition of Lys-Vasopressin as internal standard and efficient sample clean up with a mixed mode solid phase extraction (weak cation exchange), the samples were directly injected into the LC-MS system. The method was validated considering the parameters specificity, linearity, recovery (80-100%), accuracy, robustness, limit of detection/quantification (20/50 pg mL(-1)), precision (inter/intra-day<10%), ion suppression and stability. The analysis of administration study urine samples collected after a single intranasal or oral application of Dp yielded in detection windows for the unchanged target analyte for up to 20 h at concentrations between 50 and 600 pg mL(-1). Endogenous Vp was detected in concentrations of approximately 20-200 pg mL(-1) in spontaneous urine samples obtained from healthy volunteers. The general requirements of the developed method provide the characteristics for an easy transfer to other anti-doping laboratories and support closing another potential gap for cheating athletes.

Visual functions in the healthy and schizophrenic brain : from stimulus control to illusory perceptions using electrical neuroimaging

ABSTRACT (FRENCH)Ce travail de thèse basé sur le système visuel chez les sujets sains et chez les patients schizophrènes, s'articule autour de trois articles scientifiques publiés ou en cours de publication. Ces articles traitent des sujets suivants : le premier article présente une nouvelle méthode de traitement des composantes physiques des stimuli (luminance et fréquence spatiale). Le second article montre, à l'aide d'analyses de données EEG, un déficit de la voie magnocellulaire dans le traitement visuel des illusions chez les patients schizophrènes. Ceci est démontré par l'absence de modulation de la composante PI chez les patients schizophrènes contrairement aux sujets sains. Cette absence est induite par des stimuli de type illusion Kanizsa de différentes excentricités. Finalement, le troisième article, également à l'aide de méthodes de neuroimagerie électrique (EEG), montre que le traitement des contours illusoires se trouve dans le complexe latéro-occipital (LOC), à l'aide d'illusion « misaligned gratings ». De plus il révèle que les activités démontrées précédemment dans les aires visuelles primaires sont dues à des inférences « top- down ».Afin de permettre la compréhension de ces trois articles, l'introduction de ce manuscrit présente les concepts essentiels. De plus des méthodes d'analyses de temps-fréquence sont présentées. L'introduction est divisée en quatre parties : la première présente le système visuel depuis les cellules retino-corticales aux deux voix du traitement de l'information en passant par les régions composant le système visuel. La deuxième partie présente la schizophrénie par son diagnostic, ces déficits de bas niveau de traitement des stimuli visuel et ces déficits cognitifs. La troisième partie présente le traitement des contours illusoires et les trois modèles utilisés dans le dernier article. Finalement, les méthodes de traitement des données EEG seront explicitées, y compris les méthodes de temps-fréquences.Les résultats des trois articles sont présentés dans le chapitre éponyme (du même nom). De plus ce chapitre comprendra les résultats obtenus à l'aide des méthodes de temps-fréquenceFinalement, la discussion sera orientée selon trois axes : les méthodes de temps-fréquence ainsi qu'une proposition de traitement de ces données par une méthode statistique indépendante de la référence. La discussion du premier article en montrera la qualité du traitement de ces stimuli. La discussion des deux articles neurophysiologiques, proposera de nouvelles d'expériences afin d'affiner les résultats actuels sur les déficits des schizophrènes. Ceci pourrait permettre d'établir un marqueur biologique fiable de la schizophrénie.ABSTRACT (ENGLISH)This thesis focuses on the visual system in healthy subjects and schizophrenic patients. To address this research, advanced methods of analysis of electroencephalographic (EEG) data were used and developed. This manuscript is comprised of three scientific articles. The first article showed a novel method to control the physical features of visual stimuli (luminance and spatial frequencies). The second article showed, using electrical neuroimaging of EEG, a deficit in spatial processing associated with the dorsal pathway in chronic schizophrenic patients. This deficit was elicited by an absent modulation of the PI component in terms of response strength and topography as well as source estimations. This deficit was orthogonal to the preserved ability to process Kanizsa-type illusory contours. Finally, the third article resolved ongoing debates concerning the neural mechanism mediating illusory contour sensitivity by using electrical neuroimaging to show that the first differentiation of illusory contour presence vs. absence is localized within the lateral occipital complex. This effect was subsequent to modulations due to the orientation of misaligned grating stimuli. Collectively, these results support a model where effects in V1/V2 are mediated by "top-down" modulation from the LOC.To understand these three articles, the Introduction of this thesis presents the major concepts used in these articles. Additionally, a section is devoted to time-frequency analysis methods not presented in the articles themselves. The introduction is divided in four parts. The first part presents three aspects of the visual system: cellular, regional, and its functional interactions. The second part presents an overview of schizophrenia and its sensoiy-cognitive deficits. The third part presents an overview of illusory contour processing and the three models examined in the third article. Finally, advanced analysis methods for EEG are presented, including time- frequency methodology.The Introduction is followed by a synopsis of the main results in the articles as well as those obtained from the time-frequency analyses.Finally, the Discussion chapter is divided along three axes. The first axis discusses the time frequency analysis and proposes a novel statistical approach that is independent of the reference. The second axis contextualizes the first article and discusses the quality of the stimulus control and direction for further improvements. Finally, both neurophysiologic articles are contextualized by proposing future experiments and hypotheses that may serve to improve our understanding of schizophrenia on the one hand and visual functions more generally.

Concomitant calcium entry blockade and inhibition of the renin-angiotensin system: a rational and effective means for treating hypertension

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists (CAs) and blockers of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (ARBs)] are widely used today to initiate antihypertensive treatment but, when given as monotherapy, do not suffice in most patients to normalise blood pressure (BP). Combining a CA and either an ACE-inhibitor or an ARB considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. Several fixed-dose combinations are available (CA + ACE-inhibitors: amlodipine + benazepril, felodipine + ramipril, verapamil + trandolapril; CA + ARB: amlodipine + valsartan). They are expected not only to improve BP control, but also to facilitate long-term adherence with antihypertensive therapy, thereby providing maximal protection against the cardiovascular and renal damage caused by high BP.