Sex, politics and social change in the eighteenth and the nineteenth centuries: Evidence from the Swiss Alps

The 18th century "sexual revolution" can not simply be explained as a consequence of economic or institutional factors - industrialization, agricultural revolution, secularization or legal hindrances to marriages: the example of western Valais (Switzerland) shows that we have to deal with a complex configuration of factors The micro-historical approach reveals that in the 18th and 19th century sexuality - and above all illicit sexuality - was a highly subversive force which was considerably linked to political innovation and probably more generally to historical change. Non-marital sexuality was clearly tied to political dissent ant to innovative ways of behaviour, both among the social elites and the common people. This behaviour patterns influenced crucial evolutions in the social, cultural and economic history of the region.

Kinship, ritual kinship and political milieus in an alpine Valley in 19th century

In my paper I will present some results about ritual kinship and political mobilization of popular groups in an alpine Valley: the Val de Bagnes, in the Swiss canton of Valais. There are two major reasons to choose the Val de Bagnes for our inquiry about social networks: the existence of sharp political and social conflicts during the 18th and the 19th century and the availability of almost systematic genealogical data between 1700 and 1900. The starting point of my research focuses on this question: what role did kinship and ritual kinship play in the political mobilization of popular groups and in the organization of competing factions? This question allows us to shed light on some other uses and meanings of ritual kinship in the local society. Was ritual kinship a significant instrument for economic cooperation? Or was it a channel for patronage or for privileged social contacts? The analysis highlights the importance of kinship and godparentage for the building of homogeneous social and political networks. If we consider transactions between individuals, the analysis of 19th century Val de Bagnes gives the impression of quite open networks. Men and women tried to diversify their relations in order to avoid strong dependency from powerful patrons. Nevertheless, when we consider the family networks, we can notice that most relations took place in a structured social space or a specific "milieu", were intense contacts enhanced trust, although political allegiances and social choices were not fully predictable on the basis of such preferential patterns. In a politically conflictual society, like 19th century Bagnes, ritual kinship interacted with kinship solidarities and ideological factors shaping dense social networks mostly based on a common political orientation. Such milieus sustained the building of political factions, which show surprising stability over time. In this sense, milieus are important factors to understand political and religious polarization in 19th century Switzerland.

Food habits and sport activity during adolescence: differences between athletic and non-athletic teenagers in Switzerland.

OBJECTIVE: To describe food habits and dietary intakes of athletic and non-athletic adolescents in Switzerland. SETTING: College, high schools and professional centers in the Swiss canton of Vaud. METHOD: A total of 3,540 subjects aged 9-19 y answered a self-reported anonymous questionnaire to assess lifestyles, physical plus sports activity and food habits. Within this sample, a subgroup of 246 subjects aged 11-15 also participated in an in-depth ancillary study including a 3 day dietary record completed by an interview with a dietician. RESULTS: More boys than girls reported engaging in regular sports activities (P<0.001). Adolescent food habits are quite traditional: up to 15 y, most of the respondents have a breakfast and eat at least two hot meals a day, the percentages decreasing thereafter. Snacking is widespread among adolescents (60-80% in the morning, 80-90% in the afternoon). Food habits among athletic adolescents are healthier and also are perceived as such in a higher proportion. Among athletic adolescents, consumption frequency is higher for dairy products and ready to eat (RTE) cereals, for fruit, fruit juices and salad (P<0.05 at least). Thus the athletic adolescent's food brings more micronutrients than the diet of their non-athletic counterparts. Within the subgroup (ancillary study), mean energy intake corresponds to requirements for age/gender group. CONCLUSIONS: Athletic adolescents display healthier food habits than non-athletic adolescents: this result supports the idea that healthy behavior tends to cluster and suggests that prevention programs among this age group should target simultaneously both sports activity and food habits.

Electro-cortical modulations and fronto-parietal activity during motor transitions in the elderly

With aging, bimanual movements are performed with increased cerebral activity in frontal and parietal areas. In contrast, motor switching is poorly documented and is expected to engage increasing resources in the elderly. In this study, spontaneous electroencephalographic activity (EEG) was recorded while 39 young participants (YP) and 37 elderly (EP) performed motor transitions from unimanual tapping to symmetric bimanual tapping (= Activation), and opposite (= Inhibition). We measured the delay of switching using the mean and standard deviation of transition time (meanTT and sdTT). Task-related power (TRPow) in alpha frequency band (8-12Hz) was used to measure electro-cortical changes, negative values corresponding to increased cerebral activity. A balance index (BI) was computed between frontal and parietal regions, values non-significantly different from "zero" representing a comparable level of cerebral activity in these regions. The results reveal higher sdTT 1) in EP compared to YP in both transitions, 2) in Activation compared to Inhibition in both groups. TRPow tends to reach greater negative values (p=0.052) in EP compared to YP in both tapping modes and both motor transitions. Furthermore, the results show more negative TRPow 1) in both motor transitions compared to the tapping movements and 2) in frontal region for YP compared to EP during Inhibition only. BI values differ significantly from "zero" for YP in Inhibition only. In conclusion, motor transitions are more variable and tend to be resource-consuming in the elderly. Moreover, the cerebral activity spreading in EP characterized by similar level of activity between frontal and parietal regions suggest reduced capacity to recruit specialized neural mechanisms during motor inhibition.

Activité physique et sportive à l'adolescence: un défi pour les médecins, un défi pour la société. [Sports activity during adolescence: a challenge for health professionals and for the society]

The rate of teenagers who engage in sports activity on a regular basis has decreased since ten years, whereas the rate of overweight and obesity is steadily increasing. This paper discusses the meaning as well as the limits of sports activity during adolescence. Guidelines for sports participation include: a discussion of the frequency and duration of sports training sessions, which have to be adapted to the growth and pubertal stage of the adolescent. Any symptoms suggesting overuse should be tackled seriously. Physician's counselling in the field of protective behaviour (injury prevention) is effective. Finally, the majority of chronic conditions are compatible with moderate sports activity.

(.)VO(2) and EMG activity kinetics during moderate and severe constant work rate exercise in trained cyclists.

The purpose of this study was to compare O(2) uptake ((.)VO(2)) and muscle electromyography activity kinetics during moderate and severe exercise to test the hypothesis of progressive recruitment of fast-twitch fibers in the explanation of the VO(2) slow component. After an incremental test to exhaustion, 7 trained cyclists (mean +/- SD, 61.4 +/- 4.2 ml x min(-1) x kg(- 1)) performed several square-wave transitions for 6 min at moderate and severe intensities on a bicycle ergometer. The (.)VO(2) response and the electrical activity (i.e., median power frequency, MDF) of the quadriceps vastus lateralis and vastus medialis of both lower limbs were measured continuously during exercise. After 2 to 3 min of exercise onset, MDF values increased similarly during moderate and severe exercise for almost all muscles whereas a (.)VO(2) slow component occurred during severe exercise. There was no relationship between the increase of MDF values and the magnitude of the (.)VO(2) slow component during the severe exercise. These results suggest that the origin of the slow component may not be due to the progressive recruitment of fast-twitch fibers.

Cruveilhier's legacy to skull base surgery: premise of an evidence-based neuropathology in the 19th century.

OBJECTIVES: Jean Cruveilhier has always been described as a pioneer in pathological anatomy. Almost nothing has been reported concerning his exceptional methodology allying pre-mortem clinical description and syndromic classification of neurological and neurosurgical diseases, and post-mortem meticulous dissections. Cruveilhier's methodology announced the birth of the anatomoclinical method built up by Jean-Martin Charcot and the neurological French school during the 19th century. The aim of our work is to extract the quintessence of Cruveilhier's contributions to skull base pathology through his cogent clinical descriptions coupled with exceptional lithographs of anterior skull base, suprasellar and cerebello-pontine angle tumors. METHODS: We reviewed the masterwork of Jean Cruveilhier on pathological anatomy and we selected the chapters dedicated to central nervous system pathologies, mainly skull base diseases. A systematic review was performed on Pubmed/Medline and Google Scholar using the keywords "Jean Cruveilhier", "Skull base pathology", "Anatomoclinical method". RESULTS: Among his descriptions, Cruveilhier dedicated large chapters to neurosurgical diseases including brain tumors, cerebrovascular pathologies, malformations of the central nervous system, hydrocephalus, brain infections and spinal cord compressions. CONCLUSION: This work emphasizes on the role of Jean Cruveilhier in the birth of the anatomoclinical method particularly in neuroscience during a 19th century rich of epistemological evolutions toward an evidence-based medicine, through the prism of Cruveilhier's contribution to skull base pathology.

Breakpoints in ventilation, cerebral and muscle oxygenation, and muscle activity during an incremental cycling exercise.

The aim of this study was to locate the breakpoints of cerebral and muscle oxygenation and muscle electrical activity during a ramp exercise in reference to the first and second ventilatory thresholds. Twenty-five cyclists completed a maximal ramp test on an electromagnetically braked cycle-ergometer with a rate of increment of 25 W/min. Expired gazes (breath-by-breath), prefrontal cortex and vastus lateralis (VL) oxygenation [Near-infrared spectroscopy (NIRS)] together with electromyographic (EMG) Root Mean Square (RMS) activity for the VL, rectus femoris (RF), and biceps femoris (BF) muscles were continuously assessed. There was a non-linear increase in both cerebral deoxyhemoglobin (at 56 ± 13% of the exercise) and oxyhemoglobin (56 ± 8% of exercise) concomitantly to the first ventilatory threshold (57 ± 6% of exercise, p > 0.86, Cohen's d < 0.1). Cerebral deoxyhemoglobin further increased (87 ± 10% of exercise) while oxyhemoglobin reached a plateau/decreased (86 ± 8% of exercise) after the second ventilatory threshold (81 ± 6% of exercise, p < 0.05, d > 0.8). We identified one threshold only for muscle parameters with a non-linear decrease in muscle oxyhemoglobin (78 ± 9% of exercise), attenuation in muscle deoxyhemoglobin (80 ± 8% of exercise), and increase in EMG activity of VL (89 ± 5% of exercise), RF (82 ± 14% of exercise), and BF (85 ± 9% of exercise). The thresholds in BF and VL EMG activity occurred after the second ventilatory threshold (p < 0.05, d > 0.6). Our results suggest that the metabolic and ventilatory events characterizing this latter cardiopulmonary threshold may affect both cerebral and muscle oxygenation levels, and in turn, muscle recruitment responses.

Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference

Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14âeuro"20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a âeuro~kinestheticâeuro? mechanism for UM and a âeuro~visual imageryâeuro? mechanism for BM tapping movement.

Effects of verapamil and ryanodine on activity of the embryonic chick heart during anoxia and reoxygenation.

Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated immature heart has not been investigated. Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to repeated anoxia (1 min) followed by reoxygenation (5 min). Heart rate, atrioventricular propagation velocity, ventricular shortening, velocities of contraction and relaxation, and incidence of arrhythmias were studied, recorded continuously. Addition of verapamil (10 nM), which blocks selectively sarcolemmal L-type Ca2+ channels, was expected to protect against excessive entry of extracellular Ca2+, whereas addition of ryanodine (10 nM), which opens the SR Ca2+ release channel, was expected to increase cytosolic Ca2+ concentration. Verapamil (a) had no dromotropic effect by contrast to adult heart, (b) attenuated ventricular contracture induced by repeated anoxia, (c) shortened cardioplegia induced by reoxygenation, and (d) had remarkable antiarrhythmic properties during reoxygenation specially. On the other hand, ryanodine potentiated markedly arrhythmias both during anoxia and at reoxygenation. Thus despite its immaturity, the SR seems to be functional early in the developing chick heart and involved in the reversible dysfunction induced by anoxia-reoxygenation. Moreover, Ca2+ entry through L-type channels appears to worsen arrhythmias especially during reoxygenation. These findings show that the Ca2+-handling systems involved in irregular activity in immature heart, such as the embryonic chick heart, may differ from those in the adult.

Regulation of the activity of DnaA and its role during the cell cycle of caulobacter crescentus

The initiation of chromosomal replication must be tightly regulated so that the genome is replicated only once per cell cycle. In most bacteria, DnaA binds to the origin of replication and initiates chromosomal replication. DnaA is a dual-function protein that also acts as an important transcription factor that regulates the expression of many genes in bacteria. Thus, understanding how this protein is regulated during the bacterial cell cycle is of major importance. The α-proteobacterium Caulobacter crescentus is an excellent model to study the bacterial cell cycle, mainly because it is possible to isolate synchronized cell cultures and because it initiates the replication of its chromosome once per cell cycle and at a specific time of the cell cycle. This latest feature is of special interest for the major aim of my thesis work, which focused on the temporal and spatial regulation of the activity of the essential DnaA protein in C. crescentus. In Escherichia coli, the Hda protein converts ATP-DnaA into ADP- DnaA by stimulating the ATPase activity of DnaA, to prevent over-initiation of chromosome replication. We propose that there exists a similar mechanism in C. crescentus, which is not only involved in the temporal control of chromosome replication, but also in the control of gene expression. First, we provided evidences indicating that the hydrolysis of the ATP bound to DnaA is essential for the viability of C. crescentus. Our results suggest that ATP-DnaA promotes the initiation of chromosome replication, since we found that cells over-expressing a DnaA protein with a mutated ATPase domain, DnaA(R357A), over-initiated chromosome replication, unlike cells expressing the wild-type DnaA protein at similar levels. By contrast, the DnaA(R357A) protein was less active than DnaA in promoting the transcription of three essential genes, suggesting that these may be more efficiently activated by ADP-DnaA than ATP-DnaA. We propose that the ATP-DnaA to ADP-DnaA switch down-regulates the initiation of DNA replication while activating the transcription of several essential genes involved in subsequent cell cycle events. Second, we studied the role of the HdaA protein, homologous to Hda, in promoting the ATP- DnaA to ADP-DnaA switch in C. crescentus. HdaA is essential for viability and its depletion in the cell leads to an over-replication of the chromosome, indicating that HdaA is a negative regulator of DNA replication. HdaA dynamically co-localizes with the replisome. In this work, we identified DnaN, the β-clamp of the DNA polymerase, as the replisome component that interacts directly with HdaA and that recruits HdaA to the replisome in live C. crescentus cells. We also showed that a mutant HdaA protein that cannot interact or co-localize with DnaN is not functional, indicating that HdaA is probably activated by DnaN. However, we found that another non-functional HdaA protein, mutated in the conserved Arginine finger of its AAA+ domain, was able to localize at the replisome, suggesting that the AAA+ domain of HdaA exerts its essential function after the recruitment of HdaA to the replisome. We propose that HdaA stimulates the ATPase activity of DnaA once DNA replication is ongoing, via its interaction with DnaN and the activity of the two conserved R fingers of DnaA and HdaA. Finally, we created different strains in which HdaA, DnaN or DnaA were over-produced. We observed that the over-production of HdaA seems to lead to a delay in chromosome replication, while the over-production of DnaN had an opposite effect. Our results also indicate that the over-production of DnaA may intensify the over-initiation phenotype of cells depleted for HdaA. We conclude that the dynamic interplay of HdaA and DnaN in the cell contributes to regulating the ATP-DnaA/ADP-DnaA ratio in the cell, to ensure once per cell cycle initiation of chromosomal replication in C. crescentus. Altogether, our work provided important information on the regulation of the activity of DnaA in C. crescentus. Since DnaA, HdaA and DnaN are well-conserved proteins, most of our findings are useful to understand how chromosome replication and gene expression are controlled by DnaA in many other bacterial species. - L'initiation de la réplication des chromosomes doit être précisément régulée de telle sorte que le génome ne soit répliqué qu'une seule fois par cycle cellulaire. Chez la plupart des bactéries, DnaA se lie à l'origine de réplication du chromosome et en initie sa réplication. DnaA est aussi un facteur de transcription qui régule l'expression de nombreux gènes bactériens. De ce fait, il est très important de comprendre comment DnaA est régulée au cours du cycle cellulaire bactérien. L'a-protéobactérie Caulobacter crescentus est un excellent modèle pour étudier le cycle cellulaire bactérien, essentiellement parce qu'il est aisé d'isoler des populations de cellules synchronisées à la même étape du cycle cellulaire et parce que cette bactérie n'initie la réplication de son chromosome qu'une seule fois et à un moment précis de son cycle. Cette dernière caractéristique est particulièrement pertinente pour l'objectif de mon travail doctoral, qui consistait à comprendre comment l'activité de la protéine essentielle DnaA est régulée dans l'espace et dans le temps chez C. crescentus. Chez Escherichia coli, la protéine Hda convertie DnaA-ATP en DnaA-ADP en stimulant l'activité ATPasique de DnaA, ce qui empêche la sur-initiation de la réplication du chromosome. Nous proposons qu'un mécanisme similaire existe chez C. crescentus. Il serait non seulement nécessaire au contrôle de la réplication du chromosome, mais aussi au contrôle de l'expression de certains gènes. Dans un premier temps, nous avons mis en évidence le fait que l'hydrolyse de l'ATP lié à DnaA est un processus essentiel à la viabilité de C. crescentus. Nos résultats suggèrent que DnaA-ATP initie la réplication du chromosome, comme nous avons observé que des cellules qui sur-expriment une protéine DnaA(R357A) mutée sans domaine ATPasique fonctionnel, sur-initie la réplication de leur chromosome, contrairement aux cellules qui sur-expriment la protéine DnaA sauvage à des niveaux équivalents. Au contraire, la protéine DnaA(R357A) était moins active que la protéine DnaA sauvage pour promouvoir la transcription de trois gènes essentiels, ce qui suggère que ces derniers sont peut-être plus efficacement activés par DnaA-ADP que DnaA-ATP. Nous proposons que la conversion de DnaA-ATP en DnaA-ADP réprime l'initiation de la réplication, tandis qu'elle active la transcription de plusieurs gènes impliqués dans des étapes plus tardives du cycle cellulaire. Dans un deuxième temps, nous avons étudié le rôle de la protéine HdaA, homologue à Hda, dans la conversion de DnaA-ATP en DnaA-ADP chez C. crescentus. Cette protéine est essentielle à la viabilité de C. crescentus et sa déplétion donne des cellules qui sur-initient la réplication de leur chromosome, suggérant que HdaA est un répresseur de la réplication du chromosome. HdaA co-localise de manière dynamique avec le réplisome. Lors de mon travail doctoral, nous avons démontré que DnaN, le β-clamp de l'ADN polymérase, est l'élément qui recrute HdaA au réplisome in vivo. Nous avons aussi montré qu'une protéine HdaA mutante qui ne peut pas interagir ou co-localiser avec DnaN, n'est pas fonctionnelle, ce qui suggère que HdaA est activée par DnaN. Nous avons néanmoins aussi isolé une autre protéine HdaA non fonctionnelle, dont une arginine conservée de son domaine AAA+ était mutée, mais qui pouvait toujours co-localiser avec le réplisome, ce qui suggère que le domaine AAA+ de HdaA est nécessaire après le recrutement de HdaA au réplisome. Nous proposons que HdaA stimule l'activité ATPasique de DnaA qu'une fois que la réplication a commencé, grâce à son interaction avec DnaN et aux deux arginines conservées des protéines HdaA et DnaA. Finalement, nous avons construit différentes souches sur-exprimant HdaA, DnaN ou DnaA. Nous avons observé que la sur-production de HdaA retarde la réplication du chromosome, tandis que la sur-production de DnaN a un effet opposé. Nos observations suggèrent aussi que la sur-expression de DnaA dans des cellules déplétées pour HdaA aggrave leur phénotype de sur-initiation. Nous en concluons que HdaA et DnaN collaborent étroitement et de manière dynamique pour réguler le rapport DnaA-ATP/DnaA-ADP dans la cellule, pour s'assurer que la réplication du chromosome ne soit initiée qu'une seule fois par cycle cellulaire chez C. crescentus. Globalement, notre travail a mis en évidence des informations importantes sur la régulation de l'activité de DnaA chez C. crescentus. Comme DnaA, HdaA et DnaN sont des protéines très conservées, la plupart de nos découvertes sont utiles pour mieux comprendre comment la réplication du chromosome bactérien et l'expression des gènes sont contrôlées par DnaA chez de nombreuses autres espèces bactériennes.

Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.

Sleep spindles are synchronized 11-15 Hz electroencephalographic (EEG) oscillations predominant during nonrapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Ca(v)3.3-type Ca(2+) channels and Ca(2+)-dependent small-conductance-type 2 (SK2) K(+) channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-overexpressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared with wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow waves (<4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles.

Effectiveness of three different walking prescription durations on total physical activity in normal- and overweight women.

OBJECTIVE: While there is a dose-response relationship between physical activity (PA) and health benefit, little is known about the effectiveness of different PA prescriptions on total daily PA. AIM: To test, under real-life conditions and using an objective, non-invasive measurement technique (accelerometry), the effect of prescribing additional physical activity (walking only) of different durations (30, 60 and 90 min/day) on compliance (to the activity prescribed) and compensation (to total daily PA). Participants in each group were prescribed 5 sessions of walking per week over 4 weeks. METHODS: 55 normal-weight and overweight women (mean BMI 25 ± 5 kg/m(2), height 165 ± 1 cm, weight 68 ± 2 kg and mean age 27 ± 1 years) were randomly assigned to 3 prescription groups: 30, 60 or 90 min/day PA. RESULTS: Walking duration resulted in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription. Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions. In parallel, degree of compensation subsequent to exercise increased progressively as length of prescription increased. CONCLUSION: A 30-min prescription of extra walking 5 times per week was well tolerated. However, in order to increase total PA further, much more than 60 min of walking may need to be prescribed in the majority of individuals. While total exercise 'volume' increased with prescriptions longer than 30 min, compliance to the prescription decreased and greater compensation was evident. © 2014 S. Karger GmbH, Freiburg.