Birth records from Swiss married couples analyzed over of the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened

RésuméIntroduction : Le travail de thèse est un article publié dans le journal « Fertility & Sterility » s'intitulant « Birth records from Swiss married couples analyzed over the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened ».Méthodes : Les données concernant l'âge auquel les femmes mariées donnaient naissance ont été obtenues de l'Office fédéral de la statistique. Nous avons examiné la période allant de 1969 à 2006. Cet intervalle de temps choisi nous a permis de prendre en considération un total de 2'716'370 naissances. L'âge moyen des parturientes à la naissance de leur 1er, 2ème et 3ème enfant a été calculé pour chaque année à l'aide du logiciel Excel. Grâce à ces données on a pu obtenir les intervalles inter-gestationnels théoriques entre le 1er et 2ème enfant, ainsi qu'entre le 2ème et 3ème enfant.Résultats : Nous pouvons constater que l'intervalle inter-gestationnel théorique entre la première et la deuxième grossesse était de 23.2 mois en 1969 et passait à 13.0 mois en 2006. L'intervalle compris entre la deuxième et la troisième grossesse passait de 22.4 mois en 1969 à 7.9 mois en 2006. Notre analyse suggère donc que c'est le facteur social qui exerce un effet plus important que le facteur biologique sur les intervalles inter-gestationnels, car ces intervalles diminuaient malgré l'augmentation de l'âge des mères à la naissance.

No experimental evidence that sibling competition induces young to switch nests in the colonial Alpine swift, Apus melba

Adoption is frequent in colonial animals where opportunities for dependent young to receive care from nonbiological parents are high. The departure of dependent young from their original family to seek adoption in neighbouring families is thought to be induced by sibling competition for access to limited resources provided by poor-quality parents. We tested this hypothesis in the colonial Alpine swift by manipulating the number of young reared per brood, with the prediction that offspring from enlarged broods switch nests more frequently than those from reduced broods. Although nestling swifts hatch with little locomotor activity, from 20 days until their first flight at 50-70 days they frequently move out of their nests to seek adoption in neighbouring families. Although nestlings reared in experimentally enlarged broods were lighter and their body mass at day 20 after hatching was more variable than in nestlings reared in reduced broods, there was no difference between the two treatments in the frequency of nests switching and in the age when nestlings switched nests for the first time. However, consistent with other evidence that nest switching by nestling swifts evolved as a strategy to reduce ectoparasite load, young from broods with naturally high numbers of the ectoparasitic louse fly Crataerina melbae were more prone to switch nests. This shows that ectoparasitism rather than sibling competition is a key proximate factor promoting the evolution of nest switching in the colonial Alpine swift. (c) 2006 The Association for the Study of Animal Behaviour Published by Elsevier Ltd. All rights reserved.

Time and temperature dependant changes in red blood cell analytes used for testing recombinant erythropoietin abuse in sports.

There has been a long debate since the introduction of blood analysis prior to major sports events, to find out whether blood samples should be analysed right away on the site of competition or whether they should be transported and analysed in an anti-doping laboratory. Therefore, it was necessary to measure blood samples and compare the results obtained right after the blood withdrawal with those obtained after a few hours delay. Furthermore, it was interesting to determine the effect of temperature on the possible deterioration of red blood cell analytes used for testing recombinant erythropoietin abuse. Healthy volunteers were asked to give two blood samples and one of these was kept at room temperature whereas the second one was put into a refrigerator. On a regular basis, the samples were rolled for homogenisation and temperature stabilisation and were analysed with the same haematological apparatus. The results confirmed that blood controls prior to competition should be performed as soon as possible with standardised pre-analytical conditions to avoid too many variations notably on the haematocrit and the reticulocyte count. These recommendations should ideally also be applied to the all the blood controls compulsory for the medical follow up, otherwise unexplainable values could be misinterpreted and could for instance lead to a period of incapacity.

Existence and uniqueness of viscosity solution for Hamilton-Jacobi equation with discontinuous coefficients dependent on time

The main result is a proof of the existence of a unique viscosity solution for Hamilton-Jacobi equation, where the hamiltonian is discontinuous with respect to variable, usually interpreted as the spatial one. Obtained generalized solution is continuous, but not necessarily differentiable.

Stochastic time-concentration activity models for cytotoxicity in 3D brain cell cultures.

BACKGROUND: In vitro aggregating brain cell cultures containing all types of brain cells have been shown to be useful for neurotoxicological investigations. The cultures are used for the detection of nervous system-specific effects of compounds by measuring multiple endpoints, including changes in enzyme activities. Concentration-dependent neurotoxicity is determined at several time points. METHODS: A Markov model was set up to describe the dynamics of brain cell populations exposed to potentially neurotoxic compounds. Brain cells were assumed to be either in a healthy or stressed state, with only stressed cells being susceptible to cell death. Cells may have switched between these states or died with concentration-dependent transition rates. Since cell numbers were not directly measurable, intracellular lactate dehydrogenase (LDH) activity was used as a surrogate. Assuming that changes in cell numbers are proportional to changes in intracellular LDH activity, stochastic enzyme activity models were derived. Maximum likelihood and least squares regression techniques were applied for estimation of the transition rates. Likelihood ratio tests were performed to test hypotheses about the transition rates. Simulation studies were used to investigate the performance of the transition rate estimators and to analyze the error rates of the likelihood ratio tests. The stochastic time-concentration activity model was applied to intracellular LDH activity measurements after 7 and 14 days of continuous exposure to propofol. The model describes transitions from healthy to stressed cells and from stressed cells to death. RESULTS: The model predicted that propofol would affect stressed cells more than healthy cells. Increasing propofol concentration from 10 to 100 μM reduced the mean waiting time for transition to the stressed state by 50%, from 14 to 7 days, whereas the mean duration to cellular death reduced more dramatically from 2.7 days to 6.5 hours. CONCLUSION: The proposed stochastic modeling approach can be used to discriminate between different biological hypotheses regarding the effect of a compound on the transition rates. The effects of different compounds on the transition rate estimates can be quantitatively compared. Data can be extrapolated at late measurement time points to investigate whether costs and time-consuming long-term experiments could possibly be eliminated.

Improving the accuracy of heat balance integral methods applied to thermal problems with time dependent boundary conditions

In this paper the two main drawbacks of the heat balance integral methods are examined. Firstly we investigate the choice of approximating function. For a standard polynomial form it is shown that combining the Heat Balance and Refined Integral methods to determine the power of the highest order term will either lead to the same, or more often, greatly improved accuracy on standard methods. Secondly we examine thermal problems with a time-dependent boundary condition. In doing so we develop a logarithmic approximating function. This new function allows us to model moving peaks in the temperature profile, a feature that previous heat balance methods cannot capture. If the boundary temperature varies so that at some time t & 0 it equals the far-field temperature, then standard methods predict that the temperature is everywhere at this constant value. The new method predicts the correct behaviour. It is also shown that this function provides even more accurate results, when coupled with the new CIM, than the polynomial profile. Analysis primarily focuses on a specified constant boundary temperature and is then extended to constant flux, Newton cooling and time dependent boundary conditions.

Real-time imaging of regional myocardial function using fast-SENC.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia.

Fixed rings and strictures in Eosinophilic Esophagitis develop due to continuing inflammation over time

Background and Aims: Two distinct e ndoscopic phenotypes of E osinophilic Esophagitis (EoE) h ave been identified: t he inflammatory (IP) a nd the stenosing (SP) p henotype. I t is not known whether these EoE-associated phenotypes are reflective of different phases during disease course. We aimed to assess the phenotype a t initial EoE p resentation and d iagnosis and to evaluate if SP increases over time. Methods: R etrospective a nalysis of t he Swiss EoE Database (SEED) extended b y a review of p atients charts, endoscopy and pathology records. Results: F orty-four E oE p atients were a nalyzed (33 males, mean age at index visit 41 ± 14 years, all Caucasians). Median follow-up t ime was 3.1 years (IQR 1-4, r ange 1 -18 years). Median diagnostic delay w as 5 y ears (IQR 2-16, range 0-34 years). A t first diagnosis, 3 2% ( 14/44) o f EoE patients h ad already presented w ith a stenosis. T he mean d iameter o f the stenoses w as 1 0 ± 2 mm, and the mean length was 2 .8 ± 2 .9 cm. Peak e osinophil count d id n ot c hange over t ime (48 ± 39 eos/HPF at index visit vs. 59 ± 41 eos/HPF at end of follow-up, n=44). The risk of the presence of a stenosis at index visit was 0% f or a d isease duration of 0 -4 y ears, 37% f or a d isease duration between 5-10 years and 67% f or a d isease duration >10 years (p = 0.0035, trend test). Conclusions: T he frequency of e sophageal stenoses i s proportional to the disease duration, whereas the inflammatory activity does n ot s ignificantly c hange over t ime. O ur f indings underscore the necessity to reduce diagnostic delay in EoE and to control the underlying inflammatory processes to prevent esophageal remodeling.

Monitoring of vaccine-specific gamma interferon induction in genital mucosa of mice by real-time reverse transcription-PCR.

Monitoring of T-cell responses in genital mucosa has remained a major challenge because of the absence of lymphoid aggregates and the low abundance of T cells. Here we have adapted to genital tissue a sensitive real-time reverse transcription-PCR (TaqMan) method to measure induction of gamma interferon (IFN-gamma) mRNA transcription after 3 h of antigen-specific activation of CD8 T cells. For this purpose, we vaccinated C57BL/6 mice subcutaneously with human papillomavirus type 16 L1 virus-like particles and monitored the induction of CD8 T cells specific to the L1(165-173) H-2D(b)-restricted epitope. Comparison of the responses induced in peripheral blood mononuclear cells and lymph nodes (LN) by L1-specific IFN-gamma enzyme-linked immunospot assay and TaqMan determination of the relative increase in L1-specific IFN-gamma mRNA induction normalized to the content of CD8b mRNA showed a significant correlation, despite the difference in the readouts. Most of the cervicovaginal tissues could be analyzed by the TaqMan method if normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA was used and a significant L1-specific IFN-gamma induction was found in one-third of the immunized mice. This local response did not correlate with the immune responses measured in the periphery, with the exception of the sacral LN, an LN draining the genital mucosa, where a significant correlation was found. Our data show that the TaqMan method is sensitive enough to detect antigen-specific CD8 T-cell responses in the genital mucosa of individual mice, and this may contribute to elaborate effective vaccines against genital pathogens.

Evaluation of susceptibility of pear and plum varieties and rootstocks to Ca. P. pyri and Ca. P. prunorum using Real-Time PCR

Real-time PCR was used to quantify phytoplasma concentration in fifty inoculated trees from five Prunus rootstocks and in forty-eight symptomatic pear and Japanese plum trees from orchards. Seasonal fluctuation of Ca. P. prunorum in different Prunus rootstocks, over three years, showed that the highest percentage detected by nested-PCR was in the ‘Garnem’ rootstock on nearly all sampling dates. Intra-varietal differences were also observed. Phytoplasma titer could be estimated by real time PCR in some trees of the rootstocks ‘Garnem’, ‘Barrier’, ‘GF-677’ and ‘Marianna’, and ranged from 4.7x105 to 3.18x109 phytoplasmas per gram of tissue. Quantification by real-time PCR was not possible in the ‘Cadaman’ trees analyzed, probably due to a lower phytoplasma titer in this variety. Samples from infected trees from commercial plots had different phytoplasma concentration and detection percentage depending on the variety, both being lower in ‘Fortune’ and ‘606’ Japanese plum and in ‘Blanquilla’ pear trees.

Le discours comme image : énonciation et récit "mimétique" dans le "Timée-Critias" de Platon

Problématique: Pourquoi la mise en scène complexe du Timée-Critias avec ses contextes spatio-temporels emboîtés et ses narrations enchâssées? Quelle est la fonction (pragmatique et argumentative) du discours cosmogonique et anthropogonique de Timée intercalé entre le résumé du récit de l'Atlantide dans le prologue du Timée et la narration même de ce récit dans le Critias! Quel est le rapport entre les discours des deux protagonistes et celui de Socrate sur la cité idéale dans la République? Voilà les principales questions auxquelles cette thèse essaie de répondre. Grâce à une approche discursive et sémio-narrative, elle cherche à montrer la fonction pragmatique et la cohérence narrative et sémantique du double dialogue tout en tenant compte des visions du monde divergentes et même contradictoires des deux protagonistes. Elle essaie de comprendre comment les deux, l'un d'origine italique, l'autre Athénien, dans un contexte énonciatif donné et sur la base de leurs conceptions culturelles et «scientifiques» - sur l'homme et sur le monde - et de leurs idées «philosophiques» - sur l'être, le devenir et la connaissance - produisent des discours de signification différente mais traitant tous deux de la genèse, que ce soit celle du monde, de l'homme et des cités. Elle propose en outre de lire le Timée-Critias à la fois comme une continuation et une réécriture de la République: non seulement les trois dialogues ont le même sujet (la meilleure cité), mais ils se caractérisent par des parallèles dans la situation dramatique et énonciative et dans la manière dont se développe la narration. Plan: Les deux premiers chapitres examinent comment les performances discursives de Timée et de Critias se mettent en place dans le prologue, en prêtant une attention particulière aux aspects dramatiques et énonciatifs, mais aussi poétiques et narratifs (énonciateurs/narrateurs et leurs destinataires, fonction et genre des discours résumés et annoncés). Les troisième et quatrième chapitres, consacrés respectivement au long discours de Timée et à celui de Critias dans le dialogue homonyme, comparent d'abord les deux discours aux Hymnes homériques, à la Théogonie d'Hésiode et à la poésie généalogique afin de mieux saisir la fonction pragmatique et la composition de l'ensemble du Timée-Critias-, puis, à partir des principes ontologiques et épistémologiques explicités dans les proèmes, ils se proposent de dégager, en suivant de près la narration, les conceptions cosmologiques, anthropologiques et épistémologiques des deux protagonistes et de voir comment elles déterminent la production et l'énonciation de leurs discours. Enfin, le dernier chapitre reprend certains éléments essentiels étudiés précédemment en élargissant la perspective à la République et à son rapport intertextuel avec le Timée- Critias: il met en regard les contextes énonciatifs et dramatiques et la problématique des deux oeuvres (le rôle des personnages, la question de la réalisation de la meilleure cité), le discours de Timée et les livres six et sept (la khóra et Yagathón, le statut du discours vraisemblable et l'analogie de la ligne), ainsi que le Critias et les livres huit et dix (la dégénérescence de l'Atlantide et de la meilleure cité, la poésie «mimétique» de Critias et celle des poètes critiquée par Socrate).

Anaesthesia for electroconvulsive therapy: time for a change?

Introduction: Electroconvulsive therapy (ECT) may be used to treat severe depression and needs a specific general anaesthesia. Important cardiovascular changes occur during the ECT with a parasympathetic induced bradycardia followed by a sympathetic response. A dedicated protocol was designed 6 years ago. The goal of this study was to analyse the management of anaesthesia for ECT in our institution, the adherence to the protocol and the occurrence of adverse events during anaesthesia. Methods: After Institutional Ethics Committee approval, we conducted a retrospective analysis of our anaesthesia protocol for patients scheduled for electroshock therapy during a five years period (2004- 2008). The protocol includes administration of atropine subcutaneously 30 minutes before the procedure, followed by general anaesthesia induced with etomidate (0.2 mg/kg). Suxamethonium (1 mg/kg) is administered after the inflation of a pneumatic tourniquet on the opposite arm, in order to observe the electroshocks convulsive effects. The psychiatrist initiates the convulsive crisis once curarisation is achieved. Face mask ventilation is then applied during the post-ictal phase with closed blood pressure monitoring. : 228 ECT were performed in 25 patients. The median dosage of etomidate was 0.37 mg/kg and suxamethonium 1.20 mg/kg. Hypertension during the ECT procedure was present in 62.7% of cases, tachycardia 23.2% and bradycardia 10.5%. Esmolol was administered in 73.4% of hypertensive patients in a range of 0 to 30 mg. The protocol was followed in half of the cases in regards to atropine administration (50.4%). We observed a significant increase of hypertension (73.9%, p = 0.001) after atropine administration, without effect on heart rate. Conclusions: The management of anaesthesia for ECT is specific and follows a predefined protocol in our institution. Adherence to our protocol was poor. Adverse events are frequent and significant association between the administration of atropine and the incidence of hypertension as well as poor protocol adherence implies reconsideration of our anaesthesia protocol for electroconvulsive therapy and better quality control of the clinical practice.

Monitoring time-dependent degradation of phospholipids in sectioned tissues by MALDI imaging mass spectrometry.

Imaging mass spectrometry (IMS) is useful for visualizing the localization of phospholipids on biological tissue surfaces creating great opportunities for IMS in lipidomic investigations. With advancements in IMS of lipids, there is a demand for large-scale tissue studies necessitating stable, efficient and well-defined sample handling procedures. Our work within this article shows the effects of different storage conditions on the phospholipid composition of sectioned tissues from mouse organs. We have taken serial sections from mouse brain, kidney and liver thaw mounted unto ITO-coated glass slides and stored them under various conditions later analyzing them at fixed time points. A global decrease in phospholipid signal intensity is shown to occur and to be a function of time and temperature. Contrary to the global decrease, oxidized phospholipid and lysophospholipid species are found to increase within 2 h and 24 h, respectively, when mounted sections are kept at ambient room conditions. Imaging experiments reveal that degradation products increase globally across the tissue. Degradation is shown to be inhibited by cold temperatures, with sample integrity maintained up to a week after storage in −80 °C freezer under N2 atmosphere. Overall, the results demonstrate a timeline of the effects of lipid degradation specific to sectioned tissues and provide several lipid species which can serve as markers of degradation. Importantly, the timeline demonstrates oxidative sample degradation begins appearing within the normal timescale of IMS sample preparation of lipids (i.e. 1-2 h) and that long-term degradation is global. Taken together, these results strengthen the notion that standardized procedures are required for phospholipid IMS of large sample sets, or in studies where many serial sections are prepared together but analyzed over time such as in 3-D IMS reconstruction experiments.

Medicinal products: regulation of biosynthesis in space and time

We live in a "Demon-Haunted World". Human health care requires the ever increasing resistance of pathogens to be confronted by a correspondingly fast rate of discovery of novel antibiotics. One of the possible strategies towards this objective involves the rational localization of bioactive phytochemicals. The conceptual basis of the method consists in the surprisingly little known gearings of natural products with morphology, ecology and evolution of their plant source, i. e. an introspection into the general mechanisms of nature.