Sleep deprivation (SD) on focal brain ischemia in the rat : effects of different SD protocols

Sleep-wake disturbances are frequently observed in stroke patients and are associated with poorer functional outcome. Until now the effects of sleep on stroke evolution are unknown. The purpose of the present study was to evaluate the effects of three sleep deprivation (SD) protocols on brain damages after focal cerebral ischemia in a rat model. Permanent occlusion of distal branches of the middle cerebral artery was induced in adult rats. The animals were then subjected to 6h SD, 12h SD or sleep disturbances (SDis) in which 3 x 12h sleep deprivation were performed by gentle handling. Infarct size and brain swelling were assessed by Cresyl violet staining, and the number of damaged cells was measured by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Behavioral tests, namely tape removal and cylinder tests, were performed for assessing sensorimotor function. In the 6h SD protocol, no significant difference (P > 0.05) was found either in infarct size (42.5 ± 30.4 mm3 in sleep deprived animals vs. 44.5 ± 20.5 mm3 in controls, mean ± s.d.), in brain swelling (10.2 ± 3.8 % in sleep deprived animals vs. 11.3 ± 2.0 % in controls) or in number of TUNEL-positive cells (21.7 ± 2.0/mm2 in sleep deprived animals vs. 23.0 ± 1.1/mm2 in controls). In contrast, 12h sleep deprivation increased infarct size by 40 % (82.8 ± 10.9 mm3 in SD group vs. 59.2 ± 13.9 mm3 in control group, P = 0.008) and number of TUNEL-positive cells by 137 % (46.8 ± 15/mm in SD group vs. 19.7 ± 7.7/mm2 in control group, P = 0.003). There was no significant difference (P > 0.05) in brain swelling (12.9 ± 6.3 % in sleep deprived animals vs. 11.6 ± 6.0 % in controls). The SDis protocol also increased infarct size by 76 % (3 x 12h SD 58.8 ± 20.4 mm3 vs. no SD 33.8 ± 6.3 mm3, P = 0.017) and number of TUNEL-positive cells by 219 % (32.9 ± 13.2/mm2 vs. 10.3 ± 2.5/mm2, P = 0.008). Brain swelling did not show any difference between the two groups (24.5 ± 8.4 % in SD group vs. 16.7 ± 8.9 % in control group, p > 0.05). Both behavioral tests did not show any concluding results. In summary, we demonstrate that sleep deprivation aggravates brain damages in a rat model of stroke. Further experiments are needed to unveil the mechanisms underlying these effects.

Improving telecommunication security level by integrating quantum key distribution in communication protocols

Résumé La cryptographie classique est basée sur des concepts mathématiques dont la sécurité dépend de la complexité du calcul de l'inverse des fonctions. Ce type de chiffrement est à la merci de la puissance de calcul des ordinateurs ainsi que la découverte d'algorithme permettant le calcul des inverses de certaines fonctions mathématiques en un temps «raisonnable ». L'utilisation d'un procédé dont la sécurité est scientifiquement prouvée s'avère donc indispensable surtout les échanges critiques (systèmes bancaires, gouvernements,...). La cryptographie quantique répond à ce besoin. En effet, sa sécurité est basée sur des lois de la physique quantique lui assurant un fonctionnement inconditionnellement sécurisé. Toutefois, l'application et l'intégration de la cryptographie quantique sont un souci pour les développeurs de ce type de solution. Cette thèse justifie la nécessité de l'utilisation de la cryptographie quantique. Elle montre que le coût engendré par le déploiement de cette solution est justifié. Elle propose un mécanisme simple et réalisable d'intégration de la cryptographie quantique dans des protocoles de communication largement utilisés comme les protocoles PPP, IPSec et le protocole 802.1li. Des scénarios d'application illustrent la faisabilité de ces solutions. Une méthodologie d'évaluation, selon les critères communs, des solutions basées sur la cryptographie quantique est également proposée dans ce document. Abstract Classical cryptography is based on mathematical functions. The robustness of a cryptosystem essentially depends on the difficulty of computing the inverse of its one-way function. There is no mathematical proof that establishes whether it is impossible to find the inverse of a given one-way function. Therefore, it is mandatory to use a cryptosystem whose security is scientifically proven (especially for banking, governments, etc.). On the other hand, the security of quantum cryptography can be formally demonstrated. In fact, its security is based on the laws of physics that assure the unconditional security. How is it possible to use and integrate quantum cryptography into existing solutions? This thesis proposes a method to integrate quantum cryptography into existing communication protocols like PPP, IPSec and the 802.l1i protocol. It sketches out some possible scenarios in order to prove the feasibility and to estimate the cost of such scenarios. Directives and checkpoints are given to help in certifying quantum cryptography solutions according to Common Criteria.

Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506765.

The Kuramoto model: A simple paradigm for synchronization phenomena

Synchronization phenomena in large populations of interacting elements are the subject of intense research efforts in physical, biological, chemical, and social systems. A successful approach to the problem of synchronization consists of modeling each member of the population as a phase oscillator. In this review, synchronization is analyzed in one of the most representative models of coupled phase oscillators, the Kuramoto model. A rigorous mathematical treatment, specific numerical methods, and many variations and extensions of the original model that have appeared in the last few years are presented. Relevant applications of the model in different contexts are also included.

Synchronization reveals topological scales in complex networks

We study the relationship between topological scales and dynamic time scales in complex networks. The analysis is based on the full dynamics towards synchronization of a system of coupled oscillators. In the synchronization process, modular structures corresponding to well-defined communities of nodes emerge in different time scales, ordered in a hierarchical way. The analysis also provides a useful connection between synchronization dynamics, complex networks topology, and spectral graph analysis.

Self-organized criticality and synchronization in a coupled map lattice model of integrate-and-fire oscillators

We introduce two coupled map lattice models with nonconservative interactions and a continuous nonlinear driving. Depending on both the degree of conservation and the convexity of the driving we find different behaviors, ranging from self-organized criticality, in the sense that the distribution of events (avalanches) obeys a power law, to a macroscopic synchronization of the population of oscillators, with avalanches of the size of the system.

Synchronization in a lattice model of pulse-coupled oscillators

We analyze the collective behavior of a lattice model of pulse-coupled oscillators. By means of computer simulations we find the relation between the intrinsic dynamics of each member of the population and their mutual interactions that ensures, in a general context, the existence of a fully synchronized regime. This condition turns out to be the same as that obtained for the globally coupled population. When the condition is not completely satisfied we find different spatial structures. This also gives some hints about self-organized criticality.

Mechanisms of synchronization and pattern formation in a lattice of pulse-coupled oscillators

We analyze the physical mechanisms leading either to synchronization or to the formation of spatiotemporal patterns in a lattice model of pulse-coupled oscillators. In order to make the system tractable from a mathematical point of view we study a one-dimensional ring with unidirectional coupling. In such a situation, exact results concerning the stability of the fixed of the dynamic evolution of the lattice can be obtained. Furthermore, we show that this stability is the responsible for the different behaviors.

Synchronization, diversity, and topology of networks of integrate and fire oscillators

We study synchronization dynamics of a population of pulse-coupled oscillators. In particular, we focus our attention on the interplay between topological disorder and synchronization features of networks. First, we analyze synchronization time T in random networks, and find a scaling law which relates T to network connectivity. Then, we compare synchronization time for several other topological configurations, characterized by a different degree of randomness. The analysis shows that regular lattices perform better than a disordered network. This fact can be understood by considering the variability in the number of links between two adjacent neighbors. This phenomenon is equivalent to having a nonrandom topology with a distribution of interactions and it can be removed by an adequate local normalization of the couplings.

Tuning synchronization of integrate-and-fire oscillators through mobility

We analyze the emergence of synchronization in a population of moving integrate-and-fire oscillators. Oscillators, while moving on a plane, interact with their nearest neighbor upon firing time. We discover a nonmonotonic dependence of the synchronization time on the velocity of the agents. Moreover, we find that mechanisms that drive synchronization are different for different dynamical regimes. We report the extreme situation where an interplay between the time scales involved in the dynamical processes completely inhibits the achievement of a coherent state. We also provide estimators for the transitions between the different regimes.

Remote Synchronization Reveals Network Symmetries and Functional Modules

We study a Kuramoto model in which the oscillators are associated with the nodes of a complex network and the interactions include a phase frustration, thus preventing full synchronization. The system organizes into a regime of remote synchronization where pairs of nodes with the same network symmetry are fully synchronized, despite their distance on the graph. We provide analytical arguments to explain this result, and we show how the frustration parameter affects the distribution of phases. An application to brain networks suggests that anatomical symmetry plays a role in neural synchronization by determining correlated functional modules across distant locations.

A comparison of rapid bioassessment protocols used in 2 regions with Mediterranean climates, the Iberian Peninsula and South Africa

Abstract. The ability of 2 Rapid Bioassessment Protocols (RBPs) to assess stream water quality was compared in 2 Mediterranean-climate regions. The most commonly used RBPs in South Africa (SAprotocol) and the Iberian Peninsula (IB-protocol) are both multihabitat, field-based methods that use macroinvertebrates. Both methods use preassigned sensitivity weightings to calculate metrics and biotic indices. The SA- and IB-protocols differ with respect to sampling equipment (mesh size: 1000 lm vs 250 300 lm, respectively), segregation of habitats (substrate vs flow-type), and sampling and sorting procedures (variable time and intensity). Sampling was undertaken at 6 sites in South Africa and 5 sites in the Iberian Peninsula. Forty-four and 51 macroinvertebrate families were recorded in South Africa and the Iberian Peninsula, respectively; 77.3% of South African families and 74.5% of Iberian Peninsula families were found using both protocols. Estimates of community similarity compared between the 2 protocols were .60% similar among sites in South Africa and .54% similar among sites in the Iberian Peninsula (BrayCurtis similarity), and no significant differences were found between protocols (Multiresponse Permutation Procedure). Ordination based on Non-metric Multidimensional Scaling grouped macroinvertebrate samples on the basis of site rather than protocol. Biotic indices generated with the 2 protocols at each site did not differ. Thus, both RBPs produced equivalent results, and both were able to distinguish between biotic communities (mountain streams vs foothills) and detect water-quality impairment, regardless of differences in sampling equipment, segregation of habitats, and sampling and sorting procedures. Our results indicate that sampling a single habitat may be sufficient for assessing water quality, but a multihabitat approach to sampling is recommended where intrinsic variability of macroinvertebrate assemblages is high (e.g., in undisturbed sites in regions with Mediterranean climates). The RBP of choice should depend on whether the objective is routine biomonitoring of water quality or autecological or faunistic studies.

Fate of clinical research studies after ethical approval--follow-up of study protocols until publication.

BACKGROUND: Many clinical studies are ultimately not fully published in peer-reviewed journals. Underreporting of clinical research is wasteful and can result in biased estimates of treatment effect or harm, leading to recommendations that are inappropriate or even dangerous. METHODS: We assembled a cohort of clinical studies approved 2000-2002 by the Research Ethics Committee of the University of Freiburg, Germany. Published full articles were searched in electronic databases and investigators contacted. Data on study characteristics were extracted from protocols and corresponding publications. We characterized the cohort, quantified its publication outcome and compared protocols and publications for selected aspects. RESULTS: Of 917 approved studies, 807 were started and 110 were not, either locally or as a whole. Of the started studies, 576 (71%) were completed according to protocol, 128 (16%) discontinued and 42 (5%) are still ongoing; for 61 (8%) there was no information about their course. We identified 782 full publications corresponding to 419 of the 807 initiated studies; the publication proportion was 52% (95% CI: 0.48-0.55). Study design was not significantly associated with subsequent publication. Multicentre status, international collaboration, large sample size and commercial or non-commercial funding were positively associated with subsequent publication. Commercial funding was mentioned in 203 (48%) protocols and in 205 (49%) of the publications. In most published studies (339; 81%) this information corresponded between protocol and publication. Most studies were published in English (367; 88%); some in German (25; 6%) or both languages (27; 6%). The local investigators were listed as (co-)authors in the publications corresponding to 259 (62%) studies. CONCLUSION: Half of the clinical research conducted at a large German university medical centre remains unpublished; future research is built on an incomplete database. Research resources are likely wasted as neither health care professionals nor patients nor policy makers can use the results when making decisions.

Increased eeg synchronization in schizophrenia patients by the glutathione precursor, n-acetyl-cysteine

Background: Glutathione (GSH) dysregulation at the gene, protein and functional levels observed in schizophrenia patients, and schizophrenia-like anomalies in GSH deficit experimental models, suggest that genetic glutathione synthesis impairments represent one major risk factor for the disease (Do et al., 2009). In a randomized, double blind, placebo controlled, add-on clinical trial of 140 patients, the GSH precursor N-Acetyl-Cysteine (NAC, 2 g/day, 6 months) significantly improved the negative symptoms and reduced side-effects due to antipsychotics (Berk et al., 2008). In a subset of patients (n=7), NAC (2 g/day, 2 months, cross-over design) also improved auditory evoked potentials, the NMDAdependent mismatch negativity (Lavoie et al, 2008). Methods: To determine whether increased GSH levels would modulate the topography of functional brain connectivity, we applied a multivariate phase synchronization (MPS) estimator (Knyazeva et al, 2008) to dense-array EEGs recorded during rest with eyes closed at the protocol onset, the point of crossover, and at its end. Phase synchronization phenomena are appealing because they can be associated to synchronized phases while the amplitudes stay uncorrelated. MPS measures the degree of interactions among the recorded neuronal oscillators by quantifiying to what extent they behave like a macro-oscillator (i.e. the oscillators are phase synchronous). To assess the whole-head synchronization topography, we computed the MPS sensor-wise over the cluster of locations defined by the sensor itself and he surrounding ones belonging to its second-order neighborhood (Carmeli et al, 2005). Such a cluster spans about 12 cm on average. Abstracts 245 Results: The whole-head imaging revealed a specific synchronization landscape in NAC compared to placebo condition. In particular, NAC increased MPS over frontal and left temporal regions in a frequency-specific manner. Importantly, the topography and direction of MPS changes were similar and robust in all 7 patients. Moreover, these changes correlated with the changes in the Liddle's score of disorganization (Liddle, 1987) thus linking EEG synchronization to the improvement of clinical picture. Discussion: The data suggest an important pathway towards new therapeutic strategies that target GSH dysregulation in schizophrenia. They also show the utility of MPS mapping as a marker of treatment efficacy.