Trends and determinants of time in bed in Geneva, Switzerland

STUDY OBJECTIVES: There is limited information regarding sleep duration and determinants in Switzerland. We aimed to assess the trends and determinants of time in bed as a proxy for sleep duration in the Swiss canton of Geneva. METHODS: Data from repeated, independent cross-sectional representative samples of adults (≥ 18 years) of the Geneva population were collected between 2005 and 2011. Self-reported time in bed, education, monthly income, and nationality were assessed by questionnaire. RESULTS: Data from 3,853 participants (50% women, 51.7 ± 10.9 years) were analyzed. No significant trend was observed between 2005 and 2011 regarding time in bed or the prevalence of short (≤ 6 h/day) and long (> 9 h/day) time in bed. Elderly participants reported a longer time in bed (year-adjusted mean ± standard error: 7.67 ± 0.02, 7.82 ± 0.03, and 8.41 ± 0.04 h/day for 35-50, 50-65, and 65+ years, respectively, p < 0.001), while shorter time in bed was reported by non-Swiss participants (7.77 ± 0.03 vs. 7.92 ± 0.03 h/day for Swiss nationals, p < 0.001), participants with higher education (7.92 ± 0.02 for non-university vs. 7.74 ± 0.03 h/day for university, p < 0.001) or higher income (8.10 ± 0.04, 7.84 ± 0.03, and 7.70 ± 0.03 h/day for < 5,000 SFr; 5,000-9,500 SFr, and > 9,500 SFr, respectively, p < 0.001). Multivariable-adjusted polytomous logistic regression showed short and long time in bed to be positively associated with obesity and negatively associated with income. CONCLUSION: In a Swiss adult population, sleep duration as assessed by time in bed did not change significantly between 2005 and 2011. Both clinical and socioeconomic factors influence time in bed.

Strategic Adaptation in Function of Chronicity of Schizophrenic Symptoms During A Fluency Task: An fMRI Study

Background: Language processing abnormalities and executive difficulties are hallmark features of schizophrenia. The objective of this study is to assess the blood oxygenation level-dependent (BOLD) response at two different stages of the illness (i.e. comparison between adolescents and adults with schizophrenic symptoms) during a fluency task.Methods: BOLD responses during a covert verbal fluency task were compared between 11 psychotic adolescents with schizophrenic symptoms (mean age 16,9 years) and 14 adults with schizophrenia (mean age 33,4 years). fMRI data were analyzed with standard routine of spm5.Results: First, expected activation's network was found for both groups, separately. Secondly, adolescents showed greater activation in left rolandic opercule (BA 48), left angular (BA 39) and right hippocampus compared to adults. Thirdly, adults demonstrated greater activation in presupplementary motor area (BA 6) and in precentral area (BA 4) compared to adolescents.Conclusions: The adolescents seemed to recruit a verbal network (Broca and Wernicke) and memory abilities to perform a fluency task. In contrast, adults seemed to recruit more executive function abilities to perform a similar task. Despite the evolution of schizophrenia, which is known to have a deleterious influence on the prefrontal cortex development, adult patients seemed to be able to recruit such areas to perform a verbal fluency / executive function task.

β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells.

β-Catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (DCs). In this article, we demonstrate a novel role for β-catenin in directing DC subset development through IFN regulatory factor 8 (IRF8) activation. We found that splenic DC precursors express β-catenin, and DCs from mice with CD11c-specific constitutive β-catenin activation upregulated IRF8 through targeting of the Irf8 promoter, leading to in vivo expansion of IRF8-dependent CD8α(+), plasmacytoid, and CD103(+)CD11b(-) DCs. β-Catenin-stabilized CD8α(+) DCs secreted elevated IL-12 upon in vitro microbial stimulation, and pharmacological β-catenin inhibition blocked this response in wild-type cells. Upon infections with Toxoplasma gondii and vaccinia virus, mice with stabilized DC β-catenin displayed abnormally high Th1 and CD8(+) T lymphocyte responses, respectively. Collectively, these results reveal a novel and unexpected function for β-catenin in programming DC differentiation toward subsets that orchestrate proinflammatory immunity to infection.

Is the function of the serratus anterior muscle disturbed following division during a standard thoracotomy?

In a prospective study the functional results after dissection or preservation of the serratus anterior muscle in the postero-lateral standard thoracotomy were evaluated. In 14 patients of our clinic with dissection and suture and in 14 patients with preservation of the serratus muscle the muscle function was assessed and compared preoperatively, within the first two post-operative weeks, and three months after the operation by the same physiotherapists. The two groups were blinded in regard to age, original disease, and mode of intervention. We compared the wing position of the scapula in the sitting position and the positioning of the scapula at fixation of the shoulder joint in the sitting and in the supine position. Using a four-grade function assessment scheme, both groups obtained the same functional results. There was no seroma in either group. After 2.8 (2.5 to 3.0) years all the surviving patients described symmetric functional conditions. We therefore conclude that in order to achieve a better view of the operative field the serratus muscle may be dissected close to the origin if it is then readapted.

The function of a new regulator of epidermal differentiation, HOP, and pathomechanisms underlying epidermolytic hyperkeratosis

The process of epidermal differentiation involves proliferation, differentiation, migration and maturation of keratinocytes to form an impermeable barrier against water loss and outside environment. It is controlled by highly balanced regulatory machinery, involving many molecules that are still under investigation.Homeobox proteins are involved in body patterning and morphogenesis of organs and are studied as potentially good candidates to regulate this process. In the first project we investigated the role of a protein named HOP which belongs to a group of homeobox proteins. Even if HOP is a small protein almost completely composed of the homeodomain and without DNA binding capacity, it is considered as transcriptional regulator in different tissues. HOP interacts with serum response factor (SRF) and histone deacetylase type 2 (HDAC2). By microarray analysis we found that HOP expression increases in cultured human primary keratinocytes (NHK) which undergo calcium-induced differentiation. HOP protein was localized in granular layer of the epidermis of healthy individuals. Lack of HOP was demonstrated in psoriatic lesions, whereas a strong expression was demonstrated in the lesional skin of patients affected with lichen planus (LP). Since LP is characterized by hypergranulosis while psoriatic lesions by progressive lack of the granular layer, the obtained data indicated that HOP might have a potential function in granular layer of epidermis. To investigate HOP function, we inhibited its expression by using HOP specific StealthRNAi and we overexpressed HOP using lentiviral vectors in differentiating NHK. The conclusion of both experiments indicated that HOP positively regulates the expression of late differentiation markers, such as profilaggrin, loricrin and transglutaminase 1. The in vitro data were next confirmed in vivo using HOP knockout mouse model.The second part of my study involved analysis of mechanisms underlying the pathogenesis of epidermolytic hyperkeratosis (EHK). EHK is a genetic disorder characterized by erythema, skin blistering, keratinocyte hyperproliferation and hyperkeratosis. EHK is caused by mutations in keratin 1 or 10 (K1, K10) which are major structural proteins of differentiated keratinocytes and participate in the cellular scaffold formation. To investigate how the structural proteins carrying mutations alter cellular signaling, we established an in vitro model for EHK by overexpression of one of the most common K10 mutations reported so far (K10R156H), in primary human keratinocytes. In order to mimic the in vivo situation, mutated keratinocytes growing on silicone membranes were subjected to mechanical stretch. We observed strong collapse of KIF in K10R156H keratinocytes when subjected to stretch for 30 minutes. Our data demonstrated stronger activation of p38, a member of MAPK stress signaling pathways, in K10R156H when compared to control cells. We demonstrated also that K10R156H keratinocytes showed an induction of TNF-α and RANTES release in response to stretch.Taken together these studies characterize a novel regulator of epidermal differentiation - HOP and demonstrate new aspects implicated in the pathogenesis of EHK.

An essential role for the stalk region of CD8 beta in the coreceptor function of CD8.

The CD8alphabeta heterodimer is integral to the selection of the class I-restricted lineage in the thymus; however, the contribution of the CD8beta chain to coreceptor function is poorly understood. To understand whether the CD8beta membrane proximal stalk region played a role in coreceptor function, we substituted it with the corresponding sequence from the CD8alpha polypeptide and expressed the hybrid molecule in transgenic mice in place of endogenous CD8beta. Although the stalk-swapped CD8beta was expressed on the cell surface as a disulfide-bonded heterodimer at equivalent levels of expression to an endogenous CD8beta molecule, it failed to restore selection of CD8(+) class I MHC-restricted T cells and it altered the response of peripheral T cells. Thus, the stalk region of the CD8beta polypeptide has an essential role in ensuring functionality of the CD8alphabeta heterodimer and its replacement compromises the interaction of CD8 with peptide-MHC complexes.

Evaluation of the Chemical Durability of Iowa Fly Ash Concretes, HR-327, 1993

The major objective of this research project was to investigate how Iowa fly ashes influenced the chemical durability of portland cement based materials. Chemical durability has become an area of uncertainty because of the winter application of deicer salts (rock salts) that contain a significant amount of sulfate impurities. The sulfate durability testing program consisted of monitoring portland cement-fly ash paste, mortar and concrete test specimens that had been subjected to aqueous solutions containing various concentrations of salts (both sulfate and chloride). The paste and mortar specimens were monitored for length as a function of time. The concrete test specimens were monitored for length, relative dynamic modulus and mass as a function of time. The alkali-aggregate reactivity testing program consisted of monitoring the expansion of ASTM C311 mortar bar specimens that contained three different aggregates (Pyrex glass, Oreapolis and standard Ottawa sand). The results of the sulfate durability study indicated that the paste and concrete test specimens tended to exhibit surface spalling but only very slow expansive tendencies. This suggested that the permeability of the test specimens was controlling the rate of deterioration. Concrete specimens are still being monitored because the majority of the test specimens have expanded less than 0.05%; hence, this makes it difficult to estimate the service life of the concrete test specimens or to quantify the performance of the different fly ashes that were used in the study. The results of the mortar bar studies indicated that the chemical composition of the various fly ashes did have an influence on their sulfate resistance. Typically, Clinton and Louisa fly ashes performed the best, followed by the Ottumwa, Neal 4 and then Council Bluffs fly ashes. Council Bluffs fly ash was the only fly ash that consistently reduced the sulfate resistance of the many different mortar specimens that were investigated during this study. None of the trends that were observed in the mortar bar studies have yet become evident in the concrete phase of this project. The results of the alkali-aggregate study indicated that the Oreapolis aggregate is not very sensitive to alkali attack. Two of the fly ashes, Council Bluffs and Ottumwa, tended to increase the expansion of mortar bar specimens that contained the Oreapolis aggregate. However, it was not clear if the additional expansion was due to the alkali content of the fly ash, the periclase content of the fly ash or the cristobalite content of the fly ash, since all three of these factors have been found to influence the test results.

Role of the epithelial sodium channel (ENaC) in the epidermal barrier function of the skin

Abstract In humans, the skin is the largest organ of the body, covering up to 2m2 and weighing up to 4kg in an average adult. Its function is to preserve the body from external insults and also to retain water inside. This barrier function termed epidermal permeability barrier (EPB) is localized in the functional part of the skin: the epidermis. For this, evolution has built a complex structure of cells and lipids sealing the surface, the stratum corneum. The formation of this structure is finely tuned since it is not only formed once at birth, but renewed all life long. This active process gives a high plasticity and reactivity to skin, but also leads to various pathologies. ENaC is a sodium channel extensively studied in organs like kidney and lung due to its importance in regulating sodium homeostasis and fluid volume. It is composed of three subunits α, ß and r which are forming sodium selective channel through the cell membrane. Its presence in the skin has been demonstrated, but little is known about its physiological role. Previous work has shown that αENaC knockout mice displayed an abnormal epidermis, suggesting a role in differentiation processes that might be implicated in the EPB. The principal aim of this thesis has been to study the consequences for EPB function in mice deficient for αENaC by molecular and physiological means and to investigate the underlying molecular mechanisms. Here, the barrier function of αENaC knockout pups is impaired. Apparently not immediately after birth (permeability test) but 24h later, when evident water loss differences appeared compared to wildtypes. Neither the structural proteins of the epithelium nor the tights junctions showed any obvious alterations. In contrary, stratum corneum lipid disorders are most likely responsible for the barrier defect, accompanied by an impairment of skin surface acidification. To analyze in details this EPB defect, several hypotheses have been proposed: reduced sensibility to calcium which is the key activator far epidermal formation, or modification of ENaC-mediated ion fluxes/currents inside the epidermis. The cellular localization of ENaC and the action in the skin of CAPl, a positive regulator of ENaC, have been also studied in details. In summary, this study clearly demonstrates that ENaC is a key player in the EPB maintenance, because αENaC knockout pups are not able to adapt to the new environment (ex utero) as efficiently as the wildtypes, most likely due to impaired of sodium handling inside the epidermis. Résumé Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses pathologies. ENaC est un canal sodique très étudié dans le rein et le poumon pour son importance dans la régulation de l'homéostasie sodique et la régulation du volume du milieu intérieur. Il est composé de 3 sous unités, α, ß et y qui forment un pore sélectif pour le sodium dans les membranes. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris dont le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la différentiation et pourrait même être impliqué dans la barrière épithéliale. Le but de cette thèse fut l'étude de la barrière dans ces souris knockouts avec des méthodes moléculaires et physiologiques et la caractérisation des mécanismes moléculaire impliqués. Dans ce travail, il a été montré que les souris mutantes présentaient un défaut de la barrière. Ce défaut n'est pas visible immédiatement à la naissance (test de perméabilité), mais 24h plus tard, lorsque les tests de perte d'eau transépithéliale montrent une différence évidente avec les animaux contrôles. Ni les protéines de structures ni les jonctions serrées de l'épiderme ne présentaient d'imperfections majeures. A l'inverse, les lipides de la couche cornée présentaient un problème de maturation (expliquant le phénotype de la barrière), certainement consécutif au défaut d'acidification à la surface de la peau que nous avons observé. D'autres mécanismes ont été explorées afin d'investiguer cette anomalie de la barrière, comme la réduction de sensibilité au calcium qui est le principal activateur de la formation de l'épiderme, ou la modification des flux d'ions entre les couches de l'épiderme. La localisation cellulaire d'ENaC, et l'action de son activateur CAPl ont également été étudiés en détails. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des knockouts ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme. Résumé tout public Chez l'homme, la peau est le plus grand organe, couvrant presque 2m2 et pesant près de 4kg chez l'adulte. Sa fonction principale est de protéger l'organisme des agressions extérieures mais également de conserver l'eau à l'intérieur du corps. Cette fonction nommée barrière épithéliale est localisée dans la partie fonctionnelle de la peau : l'épiderme. A cette fin, l'évolution s'est dotée d'une structure complexe composée de cellules et de lipides recouvrant la surface, la couche cornée. Sa formation est finement régulée, car elle n'est pas seulement produite à la naissance mais constamment renouvelée tout au long de la vie, ce qui lui confère une grande plasticité mais ce qui est également la cause de nombreuses maladies. ENaC est une protéine formant un canal qui permet le passage sélectif de l'ion sodium à travers la paroi des cellules. Il est très étudié dans le rein pour son importance dans la récupération du sel lors de la concentration de l'urine. Ce canal est présent dans la peau mais sa fonction n'y est pas connue. Des travaux précédents ont pu montrer que les souris où le gène codant pour αENaC a été invalidé présentent un épiderme pathologique, suggérant un rôle dans la peau et plus particulièrement la fonction de barrière de l'épiderme. Le but de cette thèse fut l'étude de la fonction de barrière dans ces souris mutantes, au niveau tissulaire et cellulaire. Dans ce travail, il a été montré que les souris mutantes présentaient une peau plus perméable que celle des animaux contrôles, grâce à une machine mesurant la perte d'eau à travers la peau. Ce défaut n'est visible que 24h après la naissance, mais nous avons pu montrer que les animaux mutants perdaient quasiment 2 fois plus d'eau que les contrôles. Au niveau moléculaire, nous avons pu montrer que ce défaut provenait d'un problème de maturation des lipides qui composent la barrière de la peau. Cette maturation est incomplète vraisemblablement à cause d'un défaut de mouvement des ions dans les couches les plus superficielles de l'épiderme, et cela à cause de l'absence du canal ENaC. En résumé, cette étude démontre clairement qu'ENaC est un acteur important dans la formation de la barrière épithéliale, car la peau des mutants ne s'adapte pas aussi bien que celle des sauvages au nouvel environnement ex utero à cause de la fonction d'ENaC dans les mouvements de sodium au sein même de l'épiderme.

Bayesian-MCMC inversion of time-lapse geophysical data to characterize vadose zone hydraulic behaviour

Geophysical methods have the potential to provide valuable information on hydrological properties in the unsaturated zone. In particular, time-lapse geophysical data, when coupled with a hydrological model and inverted stochastically, may allow for the effective estimation of subsurface hydraulic parameters and their corresponding uncertainties. In this study, we use a Bayesian Markov-chain-Monte-Carlo (MCMC) inversion approach to investigate how much information regarding vadose zone hydraulic properties can be retrieved from time-lapse crosshole GPR data collected at the Arrenaes field site in Denmark during a forced infiltration experiment.

The evolution, maintenance and adaptive function of genetic colour polymorphism in birds.

The hypothesis that ornaments can honestly signal quality only if their expression is condition-dependent has dominated the study of the evolution and function of colour traits. Much less interest has been devoted to the adaptive function of colour traits for which the expression is not, or is to a low extent, sensitive to body condition and the environment in which individuals live. The aim of the present paper is to review the current theoretical and empirical knowledge of the evolution, maintenance and adaptive function of colour plumage traits for which the expression is mainly under genetic control. The finding that in many bird species the inheritance of colour morphs follows the laws of Mendel indicates that genetic colour polymorphism is frequent. Polymorphism may have evolved or be maintained because each colour morph facilitates the exploitation of alternative ecological niches as suggested by the observation that individuals are not randomly distributed among habitats with respect to coloration. Consistent with the hypothesis that different colour morphs are linked to alternative strategies is the finding that in a majority of species polymorphism is associated with reproductive parameters, and behavioural, life-history and physiological traits. Experimental studies showed that such covariations can have a genetic basis. These observations suggest that colour polymorphism has an adaptive function. Aviary and field experiments demonstrated that colour polymorphism is used as a criterion in mate-choice decisions and dominance interactions confirming the claim that conspecifics assess each other's colour morphs. The factors favouring the evolution and maintenance of genetic variation in coloration are reviewed, but empirical data are virtually lacking to assess their importance. Although current theory predicts that only condition-dependent traits can signal quality, the present review shows that genetically inherited morphs can reveal the same qualities. The study of genetic colour polymorphism will provide important and original insights on the adaptive function of conspicuous traits.

Azole resistance by loss of function of the sterol Δ⁵,⁶-desaturase gene (ERG3) in Candida albicans does not necessarily decrease virulence.

The inactivation of ERG3, a gene encoding sterol Δ⁵,⁶-desaturase (essential for ergosterol biosynthesis), is a known mechanism of in vitro resistance to azole antifungal drugs in the human pathogen Candida albicans. ERG3 inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified a C. albicans clinical isolate (VSY2) with high-level resistance to azole drugs in vitro and an absence of ergosterol but normal filamentation. Sequencing of ERG3 in VSY2 revealed a double base deletion leading to a premature stop codon and thus a nonfunctional enzyme. The reversion of the double base deletion in the mutant allele (erg3-1) restored ergosterol biosynthesis and full fluconazole susceptibility in VSY2, confirming that ERG3 inactivation was the mechanism of azole resistance. Additionally, the replacement of both ERG3 alleles by erg3-1 in the wild-type strain SC5314 led to the absence of ergosterol and to fluconazole resistance without affecting filamentation. In a mouse model of disseminated candidiasis, the clinical ERG3 mutant VSY2 produced kidney fungal burdens and mouse survival comparable to those obtained with the wild-type control. Interestingly, while VSY2 was resistant to fluconazole both in vitro and in vivo, the ERG3-derived mutant of SC5314 was resistant only in vitro and was less virulent than the wild type. This suggests that VSY2 compensated for the in vivo fitness defect of ERG3 inactivation by a still unknown mechanism(s). Taken together, our results provide evidence that contrary to previous reports inactivation of ERG3 does not necessarily affect filamentation and virulence.

Schizotypal perceptual aberrations of time: correlation between score, behavior and brain activity.

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances--including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum.

Scale Effects in Hydraulic Model Tests of Rock Protected Structures, HR-119, 1970

A laboratory investigation was undertaken to determine the limiting model Reynolds number above which the scour behavior of rock protected structures can be reproduced in hydraulic models scaled according to the Froude criterion. A submerged jet was passed over an initially full scour pocket containing uniform glass spheres and the rate of scour was measured as a function of time. The dimensions of the scour pocket and jet and the particle diameters were varied as needed to maintain strict geometric similarity. For each of two different Froude numbers the Reynolds number was varied over a wide range. The normalized scour rate was found to be practically independent of the Reynolds number, R, (based on the jet velocity and particle diameter) at values of R above about 2.5 x 10^3, and to decrease with Rat smaller values. A grid placed in the jet was found to have a very strong effect on the scour rate. In an attempt to explain the effect of R on the scour behavior, turbulent pressure and velocity fluctuations were measured in air flows and water flows, respectively, over rigid scour pockets having the same geometry as those formed in the scour experiments. The normalized spectra of the fluctuations were found to be nearly independent of R, but the flow pattern was found to be very sensitive to the inlet condition, the jet deflecting upward or downward in a not wholly explainable manner. This indicates that scour behavior can be modeled only if the approach flow is also accurately modeled.