Debris flow susceptibility mapping at a regional scale

Debris flow susceptibility mapping at a regional scale has been the subject of various studies. The complexity of the phenomenon and the variability of local controlling factors limit the use of process-based models for a first assessment. GISbased approaches associating an automatic detection of the source areas and a simple assessment of the debris flow spreading may provide a substantial basis for a preliminary susceptibility assessment at the regional scale. The use of a digital elevation model, with a 10 m resolution, for the Canton de Vaud territory (Switzerland), a lithological map and a land use map, has allowed automatic identification of the potential source areas. The spreading estimates are based on basic probabilistic and energy calculations that allow to define the maximal runout distance of a debris flow.

The behavioral relevance and top-down susceptibility of early, low level multisensory interactions in humans

Abstract (English)General backgroundMultisensory stimuli are easier to recognize, can improve learning and a processed faster compared to unisensory ones. As such, the ability an organism has to extract and synthesize relevant sensory inputs across multiple sensory modalities shapes his perception of and interaction with the environment. A major question in the scientific field is how the brain extracts and fuses relevant information to create a unified perceptual representation (but also how it segregates unrelated information). This fusion between the senses has been termed "multisensory integration", a notion that derives from seminal animal single-cell studies performed in the superior colliculus, a subcortical structure shown to create a multisensory output differing from the sum of its unisensory inputs. At the cortical level, integration of multisensory information is traditionally deferred to higher classical associative cortical regions within the frontal, temporal and parietal lobes, after extensive processing within the sensory-specific and segregated pathways. However, many anatomical, electrophysiological and neuroimaging findings now speak for multisensory convergence and interactions as a distributed process beginning much earlier than previously appreciated and within the initial stages of sensory processing.The work presented in this thesis is aimed at studying the neural basis and mechanisms of how the human brain combines sensory information between the senses of hearing and touch. Early latency non-linear auditory-somatosensory neural response interactions have been repeatedly observed in humans and non-human primates. Whether these early, low-level interactions are directly influencing behavioral outcomes remains an open question as they have been observed under diverse experimental circumstances such as anesthesia, passive stimulation, as well as speeded reaction time tasks. Under laboratory settings, it has been demonstrated that simple reaction times to auditory-somatosensory stimuli are facilitated over their unisensory counterparts both when delivered to the same spatial location or not, suggesting that audi- tory-somatosensory integration must occur in cerebral regions with large-scale spatial representations. However experiments that required the spatial processing of the stimuli have observed effects limited to spatially aligned conditions or varying depending on which body part was stimulated. Whether those divergences stem from task requirements and/or the need for spatial processing has not been firmly established.Hypotheses and experimental resultsIn a first study, we hypothesized that auditory-somatosensory early non-linear multisensory neural response interactions are relevant to behavior. Performing a median split according to reaction time of a subset of behavioral and electroencephalographic data, we found that the earliest non-linear multisensory interactions measured within the EEG signal (i.e. between 40-83ms post-stimulus onset) were specific to fast reaction times indicating a direct correlation of early neural response interactions and behavior.In a second study, we hypothesized that the relevance of spatial information for task performance has an impact on behavioral measures of auditory-somatosensory integration. Across two psychophysical experiments we show that facilitated detection occurs even when attending to spatial information, with no modulation according to spatial alignment of the stimuli. On the other hand, discrimination performance with probes, quantified using sensitivity (d'), is impaired following multisensory trials in general and significantly more so following misaligned multisensory trials.In a third study, we hypothesized that behavioral improvements might vary depending which body part is stimulated. Preliminary results suggest a possible dissociation between behavioral improvements andERPs. RTs to multisensory stimuli were modulated by space only in the case when somatosensory stimuli were delivered to the neck whereas multisensory ERPs were modulated by spatial alignment for both types of somatosensory stimuli.ConclusionThis thesis provides insight into the functional role played by early, low-level multisensory interac-tions. Combining psychophysics and electrical neuroimaging techniques we demonstrate the behavioral re-levance of early and low-level interactions in the normal human system. Moreover, we show that these early interactions are hermetic to top-down influences on spatial processing suggesting their occurrence within cerebral regions having access to large-scale spatial representations. We finally highlight specific interactions between auditory space and somatosensory stimulation on different body parts. Gaining an in-depth understanding of how multisensory integration normally operates is of central importance as it will ultimately permit us to consider how the impaired brain could benefit from rehabilitation with multisensory stimula-Abstract (French)Background théoriqueDes stimuli multisensoriels sont plus faciles à reconnaître, peuvent améliorer l'apprentissage et sont traités plus rapidement comparé à des stimuli unisensoriels. Ainsi, la capacité qu'un organisme possède à extraire et à synthétiser avec ses différentes modalités sensorielles des inputs sensoriels pertinents, façonne sa perception et son interaction avec l'environnement. Une question majeure dans le domaine scientifique est comment le cerveau parvient à extraire et à fusionner des stimuli pour créer une représentation percep- tuelle cohérente (mais aussi comment il isole les stimuli sans rapport). Cette fusion entre les sens est appelée "intégration multisensorielle", une notion qui provient de travaux effectués dans le colliculus supérieur chez l'animal, une structure sous-corticale possédant des neurones produisant une sortie multisensorielle différant de la somme des entrées unisensorielles. Traditionnellement, l'intégration d'informations multisen- sorielles au niveau cortical est considérée comme se produisant tardivement dans les aires associatives supérieures dans les lobes frontaux, temporaux et pariétaux, suite à un traitement extensif au sein de régions unisensorielles primaires. Cependant, plusieurs découvertes anatomiques, électrophysiologiques et de neuroimageries remettent en question ce postulat, suggérant l'existence d'une convergence et d'interactions multisensorielles précoces.Les travaux présentés dans cette thèse sont destinés à mieux comprendre les bases neuronales et les mécanismes impliqués dans la combinaison d'informations sensorielles entre les sens de l'audition et du toucher chez l'homme. Des interactions neuronales non-linéaires précoces audio-somatosensorielles ont été observées à maintes reprises chez l'homme et le singe dans des circonstances aussi variées que sous anes- thésie, avec stimulation passive, et lors de tâches nécessitant un comportement (une détection simple de stimuli, par exemple). Ainsi, le rôle fonctionnel joué par ces interactions à une étape du traitement de l'information si précoce demeure une question ouverte. Il a également été démontré que les temps de réaction en réponse à des stimuli audio-somatosensoriels sont facilités par rapport à leurs homologues unisensoriels indépendamment de leur position spatiale. Ce résultat suggère que l'intégration audio- somatosensorielle se produit dans des régions cérébrales possédant des représentations spatiales à large échelle. Cependant, des expériences qui ont exigé un traitement spatial des stimuli ont produits des effets limités à des conditions où les stimuli multisensoriels étaient, alignés dans l'espace ou encore comme pouvant varier selon la partie de corps stimulée. Il n'a pas été établi à ce jour si ces divergences pourraient être dues aux contraintes liées à la tâche et/ou à la nécessité d'un traitement de l'information spatiale.Hypothèse et résultats expérimentauxDans une première étude, nous avons émis l'hypothèse que les interactions audio- somatosensorielles précoces sont pertinentes pour le comportement. En effectuant un partage des temps de réaction par rapport à la médiane d'un sous-ensemble de données comportementales et électroencépha- lographiques, nous avons constaté que les interactions multisensorielles qui se produisent à des latences précoces (entre 40-83ms) sont spécifique aux temps de réaction rapides indiquant une corrélation directe entre ces interactions neuronales précoces et le comportement.Dans une deuxième étude, nous avons émis l'hypothèse que si l'information spatiale devient perti-nente pour la tâche, elle pourrait exercer une influence sur des mesures comportementales de l'intégration audio-somatosensorielles. Dans deux expériences psychophysiques, nous montrons que même si les participants prêtent attention à l'information spatiale, une facilitation de la détection se produit et ce toujours indépendamment de la configuration spatiale des stimuli. Cependant, la performance de discrimination, quantifiée à l'aide d'un index de sensibilité (d') est altérée suite aux essais multisensoriels en général et de manière plus significative pour les essais multisensoriels non-alignés dans l'espace.Dans une troisième étude, nous avons émis l'hypothèse que des améliorations comportementales pourraient différer selon la partie du corps qui est stimulée (la main vs. la nuque). Des résultats préliminaires suggèrent une dissociation possible entre une facilitation comportementale et les potentiels évoqués. Les temps de réactions étaient influencés par la configuration spatiale uniquement dans le cas ou les stimuli somatosensoriels étaient sur la nuque alors que les potentiels évoqués étaient modulés par l'alignement spatial pour les deux types de stimuli somatosensorielles.ConclusionCette thèse apporte des éléments nouveaux concernant le rôle fonctionnel joué par les interactions multisensorielles précoces de bas niveau. En combinant la psychophysique et la neuroimagerie électrique, nous démontrons la pertinence comportementale des ces interactions dans le système humain normal. Par ailleurs, nous montrons que ces interactions précoces sont hermétiques aux influences dites «top-down» sur le traitement spatial suggérant leur occurrence dans des régions cérébrales ayant accès à des représentations spatiales de grande échelle. Nous soulignons enfin des interactions spécifiques entre l'espace auditif et la stimulation somatosensorielle sur différentes parties du corps. Approfondir la connaissance concernant les bases neuronales et les mécanismes impliqués dans l'intégration multisensorielle dans le système normale est d'une importance centrale car elle permettra d'examiner et de mieux comprendre comment le cerveau déficient pourrait bénéficier d'une réhabilitation avec la stimulation multisensorielle.

A Modulated Closed Form solution for Quantitative Susceptibility Mapping - A thorough evaluation and comparison to iterative methods based on edge prior knowledge.

The aim of this study is to perform a thorough comparison of quantitative susceptibility mapping (QSM) techniques and their dependence on the assumptions made. The compared methodologies were: two iterative single orientation methodologies minimizing the l2, l1TV norm of the prior knowledge of the edges of the object, one over-determined multiple orientation method (COSMOS) and anewly proposed modulated closed-form solution (MCF). The performance of these methods was compared using a numerical phantom and in-vivo high resolution (0.65mm isotropic) brain data acquired at 7T using a new coil combination method. For all QSM methods, the relevant regularization and prior-knowledge parameters were systematically changed in order to evaluate the optimal reconstruction in the presence and absence of a ground truth. Additionally, the QSM contrast was compared to conventional gradient recalled echo (GRE) magnitude and R2* maps obtained from the same dataset. The QSM reconstruction results of the single orientation methods show comparable performance. The MCF method has the highest correlation (corrMCF=0.95, r(2)MCF =0.97) with the state of the art method (COSMOS) with additional advantage of extreme fast computation time. The l-curve method gave the visually most satisfactory balance between reduction of streaking artifacts and over-regularization with the latter being overemphasized when the using the COSMOS susceptibility maps as ground-truth. R2* and susceptibility maps, when calculated from the same datasets, although based on distinct features of the data, have a comparable ability to distinguish deep gray matter structures.

Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis(1.).

Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM.

Macrophage Migration Inhibitory Factor Deficiency Is Associated With Impaired Killing of Gram-Negative Bacteria by Macrophages and Increased Susceptibility to Klebsiella pneumoniae Sepsis.

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Eosinophilic esophagitis: Updated consensus recommendations for children and adults.

Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. In 2007, a consensus recommendation provided clinical and histopathologic guidance for the diagnosis and treatment of EoE; however, only a minority of physicians use the 2007 guidelines, which require fulfillment of both histologic and clinical features. Since 2007, the number of EoE publications has doubled, providing new disease insight. Accordingly, a panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology, and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, information and recommendations were provided in each of the following areas of EoE: diagnostics, genetics, allergy testing, therapeutics, and disease complications. Because accumulating animal and human data have provided evidence that EoE appears to be an antigen-driven immunologic process that involves multiple pathogenic pathways, a new conceptual definition is proposed highlighting that EoE represents a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. The diagnostic guidelines continue to define EoE as an isolated chronic disorder of the esophagus diagnosed by the need of both clinical and pathologic features. Patients commonly have high rates of concurrent allergic diatheses, especially food sensitization, compared with the general population. Proved therapeutic options include chronic dietary elimination, topical corticosteroids, and esophageal dilation. Important additions since 2007 include genetic underpinnings that implicate EoE susceptibility caused by polymorphisms in the thymic stromal lymphopoietin protein gene and the description of a new potential disease phenotype, proton pump inhibitor-responsive esophageal eosinophila. Further advances and controversies regarding diagnostic methods, surrogate disease markers, allergy testing, and treatment approaches are discussed.

Techniques for analytical testing of unconventional samples.

Forensic scientists have long detected the presence of drugs and their metabolites in biological materials using body fluids such as urine, blood and/or other biological liquids or tissues. For doping analysis, only urine has so far been collected. In recent years, remarkable advances in sensitive analytical techniques have encouraged the analysis of drugs in unconventional biological samples such as hair, saliva and sweat. These samples are easily collected, although drug levels are often lower than the corresponding levels in urine or blood. This chapter reviews recent studies in the detection of doping agents in hair, saliva and sweat. Sampling, analytical procedures and interpretation of the results are discussed in comparison with those obtained from urine and blood samples.

A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.

AbstractBACKGROUND: KRAB-ZFPs (Krüppel-associated box domain-zinc finger proteins) are vertebrate-restricted transcriptional repressors encoded in the hundreds by the mouse and human genomes. They act via an essential cofactor, KAP1, which recruits effectors responsible for the formation of facultative heterochromatin. We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences.METHOD: To investigate this issue further we used an ectopic KRAB-based repressor. This system allowed us to tether KRAB/KAP1 to hundreds of euchromatic sites within genes, and to record its impact on gene expression. We then correlated this KRAB/KAP1-mediated transcriptional effect to pre-existing genomic and chromatin structures to identify specific characteristics making a gene susceptible to repression.RESULTS: We found that genes that were susceptible to KRAB/KAP1-mediated silencing carried higher levels of repressive histone marks both at the promoter and over the transcribed region than genes that were insensitive. In parallel, we found a high enrichment in euchromatic marks within both the close and more distant environment of these genes.CONCLUSION: Together, these data indicate that high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression.

Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Conventional therapy with beta-blockers is incompletely effective in preventing arrhythmic events in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). We have previously discovered that flecainide in addition to conventional drug therapy prevents ventricular arrhythmias in patients with genotype-positive CPVT. OBJECTIVE: To study the efficacy of flecainide in patients with genotype-negative CPVT. METHODS: We studied the efficacy of flecainide for reducing ventricular arrhythmias during exercise testing and preventing arrhythmia events during long-term follow-up. RESULTS: Twelve patients with genotype-negative CPVT were treated with flecainide. Conventional therapy failed to control ventricular arrhythmias in all patients. Flecainide was initiated because of significant ventricular arrhythmias (n = 8), syncope (n = 3), or cardiac arrest (n = 1). At the baseline exercise test before flecainide, 6 patients had ventricular tachycardia and 5 patients had bigeminal or frequent ventricular premature beats. Flecainide reduced ventricular arrhythmias at the exercise test in 8 patients compared to conventional therapy, similar to that in patients with genotype-positive CPVT in our previous report. Notably, flecainide completely prevented ventricular arrhythmias in 7 patients. Flecainide was continued in all patients except for one who had ventricular tachycardia at the exercise test on flecainide. During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. Flecainide was not discontinued owing to side effects in any of the patients. CONCLUSIONS: Flecainide was effective in patients with genotype-negative CPVT, suggesting that spontaneous Ca(2+) release from ryanodine channels plays a role in arrhythmia susceptibility, similar to that in patients with genotype-positive CPVT.

Neural activity of the anterior insula in emotional processing depends on the individuals' emotional susceptibility

Differences in personality factors between individuals may manifest themselves with different patterns of neural activity while individuals process stimuli with emotional content. We attempted to verify this hypothesis by investigating emotional susceptibility (ES), a specific emotional trait of the human personality defined as the tendency to "experience feelings of discomfort, helplessness, inadequacy and vulnerability" after exposure to stimuli with emotional valence. By administering a questionnaire evaluating the individuals' ES, we selected two groups of participants with high and low ES respectively. Then, we used functional magnetic resonance imaging to investigate differences between the groups in the neural activity involved while they were processing emotional stimuli in an explicit (focusing on the content of the stimuli) or an incidental (focusing on spatial features of the stimuli, irrespectively of their content) way. The results showed a selective difference in brain activity between groups only in the explicit processing of the emotional stimuli: bilateral activity of the anterior insula was present in subjects with high ES but not in subjects with low ES. This difference in neural activity within the anterior insula proved to be purely functional since no brain morphological differences were found between groups, as assessed by a voxel-based morphometry analysis. Although the role of the anterior insula in the processing of contexts perceived as emotionally salient is well established, the present study provides the first evidence of a modulation of the insular activity depending on the individuals' ES trait of personality.

Voriconazole-Induced Inhibition of the Fungicidal Activity of Amphotericin B in Candida Strains with Reduced Susceptibility to Voriconazole: an Effect Not Predicted by the MIC Value Alone.

An antagonistic effect of voriconazole on the fungicidal activity of sequential doses of amphotericin B has previously been demonstrated in Candida albicans strains susceptible to voriconazole. Because treatment failure and the need to switch to other antifungals are expected to occur more often in infections that are caused by resistant strains, it was of interest to study whether the antagonistic effect was still seen in Candida strains with reduced susceptibility to voriconazole. With the hypothesis that antagonism will not occur in voriconazole-resistant strains, C. albicans strains with characterized mechanisms of resistance against voriconazole, as well as Candida glabrata and Candida krusei strains with differences in their degrees of susceptibility to voriconazole were exposed to voriconazole or amphotericin B alone, to both drugs simultaneously, or to voriconazole followed by amphotericin B in an in vitro kinetic model. Amphotericin B administered alone or simultaneously with voriconazole resulted in fungicidal activity. When amphotericin B was administered after voriconazole, its activity was reduced (median reduction, 61%; range, 9 to 94%). Levels of voriconazole-dependent inhibition of amphotericin B activity differed significantly among the strains but were not correlated with the MIC values (correlation coefficient, -0.19; P = 0.65). Inhibition was found in C. albicans strains with increases in CDR1 and CDR2 expression but not in the strain with an increase in MDR1 expression. In summary, decreased susceptibility to voriconazole does not abolish voriconazole-dependent inhibition of the fungicidal activity of amphotericin B in voriconazole-resistant Candida strains. The degree of interaction could not be predicted by the MIC value alone.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Development and testing of novel chloroplast microsatellite markers for Lolium perenne and other grasses (Poaceae) from de novo sequencing and in silico sequences

Twelve primers to amplify microsatellite markers from the chloroplast genome of Lolium perenne were designed and optimized using de novo sequencing and in silico sequences. With one exception, each locus was polymorphic with a range from two to nine alleles in L. perenne. The newly developed primer pairs cross-amplified in different species of Lolium and in 50 other grass species representing nine grass subfamilies.