Numerical analysis of wave-induced fluid flow effects on seismic data: Application to monitoring of CO2 storage at the Sleipner Field

In this work we analyze how patchy distributions of CO2 and brine within sand reservoirs may lead to significant attenuation and velocity dispersion effects, which in turn may have a profound impact on surface seismic data. The ultimate goal of this paper is to contribute to the understanding of these processes within the framework of the seismic monitoring of CO2 sequestration, a key strategy to mitigate global warming. We first carry out a Monte Carlo analysis to study the statistical behavior of attenuation and velocity dispersion of compressional waves traveling through rocks with properties similar to those at the Utsira Sand, Sleipner field, containing quasi-fractal patchy distributions of CO2 and brine. These results show that the mean patch size and CO2 saturation play key roles in the observed wave-induced fluid flow effects. The latter can be remarkably important when CO2 concentrations are low and mean patch sizes are relatively large. To analyze these effects on the corresponding surface seismic data, we perform numerical simulations of wave propagation considering reservoir models and CO2 accumulation patterns similar to the CO2 injection site in the Sleipner field. These numerical experiments suggest that wave-induced fluid flow effects may produce changes in the reservoir's seismic response, modifying significantly the main seismic attributes usually employed in the characterization of these environments. Consequently, the determination of the nature of the fluid distributions as well as the proper modeling of the seismic data constitute important aspects that should not be ignored in the seismic monitoring of CO2 sequestration problems.

Melanin-based coloration is a nondirectionally selected sex-specific signal of offspring development in the Alpine swift

Two mutually exclusive hypotheses have been put forward to explain the evolution and adaptive function of melanin-based color traits. According to sexual selection theory melanism is a directionally selected signal of individual quality, whereas theory on the maintenance of genetic polymorphism proposes that alternative melanin-based variants achieve equal fitness. Alpine swift (Apus melba) males and females have a conspicuous patch of white feathers on the breast with their rachis varying continuously from white to black, and hence the breast varies from white to striated. If this trait is a sexually selected signal of quality, its expression should be condition dependent and the degree of melanism directionally selected. If variation in melanism is a polymorphism, its expression should be genetically determined and fitness of melanin-based variants equal. We experimentally tested these predictions by exchanging eggs or hatchlings between randomly chosen nests and by estimating survival and reproduction in relation to melanism. We found that breast melanism is heritable and that the environment and body condition do not significantly influence its expression. Between 5 and 50 days of age nestlings were heavier and their wings longer when breast feathers of their biological father were blacker, and they also fledged at a younger age. This shows that aspects of offspring quality covary positively with the degree of melanism. However, this did not result in directional selection because nestling survival and recruitment in the local breeding population were not associated with father breast melanism. Furthermore, adult survival, age at first reproduction and probability of skipping reproduction did not covary with the degree of melanism. Genetic variation in breast melanism is therefore maintained either because nonmelanic males achieve fitness similar to melanic males via a different route than producing fast-growing offspring, or because the advantage of producing fast-growing offspring is not sufficiently pronounced to result in directional selection.

Double-tagged fluorescent bacterial bioreporter for the study of polycyclic aromatic hydrocarbon diffusion and bioavailability.

Bacterial degradation of polycyclic aromatic hydrocarbons (PAHs), ubiquitous contaminants from oil and coal, is typically limited by poor accessibility of the contaminant to the bacteria. In order to measure PAH availability in complex systems, we designed a number of diffusion-based assays with a double-tagged bacterial reporter strain Burkholderia sartisoli RP037-mChe. The reporter strain is capable of mineralizing phenanthrene (PHE) and induces the expression of enhanced green fluorescent protein (eGFP) as a function of the PAH flux to the cell. At the same time, it produces a second autofluorescent protein (mCherry) in constitutive manner. Quantitative epifluorescence imaging was deployed in order to record reporter signals as a function of PAH availability. The reporter strain expressed eGFP proportionally to dosages of naphthalene or PHE in batch liquid cultures. To detect PAH diffusion from solid materials the reporter cells were embedded in 2 cm-sized agarose gel patches, and fluorescence was recorded over time for both markers as a function of distance to the PAH source. eGFP fluorescence gradients measured on known amounts of naphthalene or PHE served as calibration for quantifying PAH availability from contaminated soils. To detect reporter gene expression at even smaller diffusion distances, we mixed and immobilized cells with contaminated soils in an agarose gel. eGFP fluorescence measurements confirmed gel patch diffusion results that exposure to 2-3 mg lampblack soil gave four times higher expression than to material contaminated with 10 or 1 (mg PHE) g(-1).

Autophagy defect is associated with low glucose-induced apoptosis in 661W photoreceptor cells.

Glucose is an important metabolic substrate of the retina and diabetic patients have to maintain a strict normoglycemia to avoid diabetes secondary effects, including cardiovascular disease, nephropathy, neuropathy and retinopathy. Others and we recently demonstrated the potential role of hypoglycemia in diabetic retinopathy. We showed acute hypoglycemia to induce retinal cell death both in vivo during an hyperinsulinemic/hypoglycemic clamp and in vitro in 661W photoreceptor cells cultured at low glucose concentration. In the present study, we showed low glucose to induce a decrease of BCL2 and BCL-XL anti-apoptotic proteins expression, leading to an increase of free pro-apoptotic BAX. In parallel, we showed that, in retinal cells, low glucose-induced apoptosis is involved in the process of autophagosomes formation through the AMPK/RAPTOR/mTOR pathway. Moreover, the decrease of LAMP2a expression led to a defect in the autophagosome/lysosome fusion process. Specific inhibition of autophagy, either by 3-methyladenine or by down-regulation of ATG5 or ATG7 proteins expression, increased caspase 3 activation and 661W cell death. We show that low glucose modifies the delicate equilibrium between apoptosis and autophagy. Cells struggled against low nutrient condition-induced apoptosis by starting an autophagic process, which led to cell death when inhibited. We conclude that autophagy defect is associated with low glucose-induced 661W cells death that could play a role in diabetic retinopathy. These results could modify the way of addressing negative effects of hypoglycemia. Short-term modulation of autophagy could be envisioned to treat diabetic patients in order to avoid secondary complications of the disease.

New vineyard cultivation practices create patchy ground vegetation, favouring Woodlarks

Intensive agriculture, in which detrimental farming practices lessen food abundance and/or reduce food accessibility for many animal species, has led to a widespread collapse of farmland biodiversity. Vineyards in central and southern Europe are intensively cultivated; though they may still harbour several rare plant and animal species, they remain little studied. Over the past decades, there has been a considerable reduction in the application of insecticides in wine production, with a progressive shift to biological control (integrated production) and, to a lesser extent, organic production. Spraying of herbicides has also diminished, which has led to more vegetation cover on the ground, although most vineyards remain bare, especially in southern Europe. The effects of these potentially positive environmental trends upon biodiversity remain mostly unknown as regards vertebrates. The Woodlark (Lullula arborea) is an endangered, short-distance migratory bird that forages and breeds on the ground. In southern Switzerland (Valais), it occurs mostly in vineyards. We used radiotracking and mixed effects logistic regression models to assess Woodlark response to modern vineyard farming practices, study factors driving foraging micro-habitat selection, and determine optimal habitat profile to inform management. The presence of ground vegetation cover was the main factor dictating the selection of foraging locations, with an optimum around 55% at the foraging patch scale. These conditions are met in integrated production vineyards, but only when grass is tolerated on part of the ground surface, which is the case on ca. 5% of the total Valais vineyard area. In contrast, conventionally managed vineyards covering a parts per thousand yen95% of the vineyard area are too bare because of systematic application of herbicides all over the ground, whilst the rare organic vineyards usually have a too-dense sward. The optimal mosaic with ca. 50% ground vegetation cover is currently achieved in integrated production vineyards where herbicide is applied every second row. In organic production, ca. 50% ground vegetation cover should be promoted, which requires regular mechanical removal of ground vegetation. These measures are likely to benefit general biodiversity in vineyards.

Analyse économique et comportements à risque

Introduction Le cadre conceptuel de l'analyse économique considère que l'individu prend des décisions en mettant en balance les avantages et les inconvénients que ces décisions présentent pour lui. En s'appuyant sur ses préférences et en intégrant ses contraintes (matérielles, physiques, externes, etc.), il choisit d'effectuer ou non une action, d'adopter ou pas un comportement, de façon à ce que les conséquences de ses choix maximisent sa satisfaction. Le fait qu'un individu adopte un certain comportement révèle donc le caractère positif pour lui des conséquences de ce comportement. C'est le postulat méthodologique de rationalité du consommateur, fondement de toute analyse économique. L'adoption par un individu d'un comportement qui implique un risque pour son bien-être physique ou mental suit le même schéma d'analyse. Il résulte d'un arbitrage inter temporel entre la satisfaction que procure ce comportement et le coût du risque associé. Ce risque se définit par la combinaison de la probabilité d'occurrence de l'événement redouté avec la gravité de ses conséquences. En adoptant un comportement à risque, l'individu révèle donc que ce comportement a pour lui un impact net positif. Certains comportements à risque, comme la consommation de tabac et, plus largement, de psychotropes, engendrent une dépendance à même de brider le libre-arbitre du consommateur. Un individu peut être amené à consommer un produit alors même que sa raison lui dicte de ne pas le faire. Ces comportements ont longtemps été considérés par les économistes comme extérieurs au champ d'analyse de leur discipline, la dépendance paraissant antinomique avec le concept de rationalité du consommateur. Par son modèle de dépendance rationnelle, Gary Stanley Becker prend le contre-pied de cette approche en montrant qu'un comportement de dépendance pouvait parfaitement s'expliquer par la maximisation de la fonction de satisfaction d'un individu rationnel et informé. Il postule que les consommateurs de stupéfiants sont conscients des conséquences futures de leurs décisions présentes, tant du point de vue de leur santé que de celui de la dépendance. Dans ce modèle, la dépendance implique deux effets le renforcement et la tolérance. Le renforcement signifie que plus un bien a été consommé dans le passé, plus l'augmentation de sa consommation courante est valorisée. En d'autres termes, l'utilité marginale de la consommation courante augmente avec la consommation antérieure. La tolérance traduit le fait qu'un individu habitué à la consommation d'un bien tirera d'une consommation donnée une satisfaction inférieure par rapport à un individu qui a peu consommé par le passé. Dans l'exemple du tabagisme, l'effet de renforcement implique qu'un grand fumeur ressent une forte envie de fumer, mais que plus il a fumé dans le passé, plus le plaisir qu'il ressent en fumant une quantité donnée de cigarettes diminue. Le premier effet explique le phénomène de manque et le second explique pourquoi la satisfaction qu'un fumeur retire de sa consommation de cigarettes tend à diminuer avec le temps. Selon Becker, l'individu choisit de devenir dépendant : il sait que sa consommation présente de cigarettes contraint ses choix futurs et il détermine au départ sa consommation sur l'ensemble de sa vie. Cependant, ce modèle n'est pas compatible avec les regrets exprimés par de nombreux fumeurs et les tentatives infructueuses de sevrage souvent concomitantes. Un fumeur qui anticiperait parfaitement le phénomène de dépendance arrêterait de fumer à la date voulue, à sa première tentative. Partant de ce constat, Athanasios Orphanides a construit un modèle dans lequel les fumeurs peuvent se retrouver prisonniers de leur consommation par des anticipations imparfaites du pouvoir addictif du tabac. Leur théorie suppose que les individus ne sont pas tous sujets de la même manière à la dépendance, que chacun a une perception subjective de son risque de dépendance et que cette perception évolue constamment durant la période de consommation du bien addictif. Dans ce contexte, un individu qui maximise des préférences stables, mais qui sous-estime le potentiel addictif d'un produit peut devenir dépendant par accident et regretter ensuite cette dépendance. Le modèle de Becker ou celui d'Orphanides ont des conséquences très différentes sur l'action régulatrice que doit ou non jouer l'État sur le marché d'un bien addictif. Si, comme Becker, on considère que les consommateurs sont rationnels et parfaitement informés des conséquences de leurs actes, l'action du régulateur devrait se limiter à l'internalisation du coût externe que les fumeurs font peser sur la société. Si le fumeur est conscient du risque qu'il prend et que pour lui le plaisir qu'il retire de cette consommation dépasse le déplaisir engendré par ses conséquences, une intervention du régulateur reposerait sur une base paternaliste, l'État posant alors un jugement de valeur sur les préférences des individus. En revanche, si on considère, comme dans la modélisation d'Orphanides, que les fumeurs sous-estiment le phénomène de dépendance lorsqu'ils décident de se mettre à fumer, un marché non régulé conduit à une consommation supérieure à celle qui prévaudrait en information parfaite. Certains fumeurs peuvent ainsi se retrouver accrochés à leur consommation de tabac, sans que cela ait été leur but. Dans cette perspective, l'État est légitimé à intervenir par des politiques de lutte contre le tabagisme, afin de compenser les erreurs d'anticipation des individus. Cette thèse propose d'appliquer les outils de l'analyse économique à des problématiques de santé publique dans le domaine des comportements à risque et en particulier du tabagisme. Elle a pour finalité d'apporter de nouveaux éléments de connaissance permettant d'éclairer certains choix de régulation dans ce domaine. Le premier chapitre est une analyse coût-efficacité des thérapies médicamenteuses de soutien à la désaccoutumance tabagique. Comme nous l'avons vu plus haut, certains fumeurs se trouvent piégés dans leur consommation par le phénomène de dépendance et ont des difficultés à arrêter de fumer. Ces dernières années, plusieurs médicaments de soutien au fumeur en phase de sevrage ont fait leur apparition. Parmi eux, on compte des substituts nicotiniques sous forme de gomme, patch, spray ou inhalateur, mais aussi un antidépresseur ne contenant pas de nicotine. Ces traitements présentent des efficacités et des coûts différents. L'évaluation économique en santé permet de calculer un indicateur unique d'efficience qui synthétise l'efficacité d'un traitement et son coût. Cette méthode permet de comparer différents types de prises en charge médicales d'une même pathologie, mais aussi de comparer des interventions thérapeutiques dans des domaines différents. Nous développons un modèle de Markov pour estimer le gain en année de vie d'une stratégie de prévention du tabagisme. Ce modèle permet de simuler le devenir d'une cohorte de fumeurs en fonction du type de soutien à la désaccoutumance qui leur est proposé. Sur cette base, nous calculons le coût par année de vie gagnée de chaque type d'intervention. Les résultats permettent de classer les cinq types de prise en charge selon leur efficience, mais aussi de les comparer à d'autres interventions de prévention dans des domaines différents. Le deuxième chapitre traite des corrélations entre le niveau de formation des individus et leur consommation de tabac. Sur un plan épidémiologique, on constate que les personnes qui atteignent un niveau de formation plus élevé ont une propension à fumer plus faible que les autres. Peut-on en conclure qu'il existe une relation causale inverse entre formation et tabagisme ? Sous l'angle de la théorie économique, il existe deux principales hypothèses à même d'expliquer cette corrélation. La première hypothèse repose sur le modèle de capital santé développé par Michael Grossman au début des années 1970. Dans ce modèle, l'individu dispose d'un stock de santé qui se déprécie avec le temps. Ce stock peut être augmenté grâce à des dépenses en soins médicaux ou à des investissements en temps consacré à l'amélioration de sa santé. La formation a pour effet d'augmenter l'efficacité des investissements en santé. Dans le cas du tabac, Grossman considère que des individus mieux formés auront une meilleurs information sur les méfaits du tabac sur la santé, ce qui tendra à diminuer leur consommation de tabac. La seconde hypothèse ne considère pas un lien causal entre la formation et la santé, mais repose sur l'existence d'une tierce variable qui influencerait parallèlement, et dans un sens opposé, le niveau de formation et la propension à fumer. Cette tierce variable est le taux de préférence pour le présent. Pour un individu fortement tourné vers le présent, l'investissement en temps de formation a un coût relativement élevé dans la mesure où il doit sacrifier du revenu aujourd'hui pour obtenir un revenu plus élevé demain. Parallèlement, il pondère moins fortement la santé future et a donc une plus forte propension à fumer. Nous développons une méthode économétrique qui permet de séparer l'effet de causalité de l'effet de sélection. Le troisième chapitre traite du rôle des interactions sociales dans les comportements à risque des adolescents. La théorie économique considère que chaque individu définit seul ses choix de consommation en maximisant sa fonction d'utilité. Cela ne signifie pas pour autant qu'il soit insensible aux influences extérieures, notamment au comportement de son entourage. Dans certaines situations et pour certains produits, l'utilité que procure la consommation d'un bien est corrélée avec le nombre de personnes qui consomment ce même bien dans l'entourage. En d'autres termes, la consommation des autres, augmente la valeur que l'on attribue à un bien. Ce mécanisme est souvent appliqué à l'analyse des comportements à risque des adolescents et du rôle que peut y jouer le groupe des pairs. Si cet impact est bien connu du point de vue théorique, il est beaucoup plus difficile de le quantifier sur un plan empirique. Pour identifier cet effet, nous développons une méthodologie économétrique, originale dans ce contexte, qui permet de séparer l'effet individuel de l'effet d'influence des pairs dans l'adoption d'un comportement à risque. Nous appliquons cette méthode aux trois comportements à risque que sont la consommation de tabac, d'alcool et de cannabis chez les adolescents.

Gauge transformations in the Lagrangian and Hamilton formalisms of generally covariant theories

We study spacetime diffeomorphisms in the Hamiltonian and Lagrangian formalisms of generally covariant systems. We show that the gauge group for such a system is characterized by having generators which are projectable under the Legendre map. The gauge group is found to be much larger than the original group of spacetime diffeomorphisms, since its generators must depend on the lapse function and shift vector of the spacetime metric in a given coordinate patch. Our results are generalizations of earlier results by Salisbury and Sundermeyer. They arise in a natural way from using the requirement of equivalence between Lagrangian and Hamiltonian formulations of the system, and they are new in that the symmetries are realized on the full set of phase space variables. The generators are displayed explicitly and are applied to the relativistic string and to general relativity.

Effects of fructose on hepatic glucose metabolism in humans.

Hepatic and extrahepatic insulin sensitivity was assessed in six healthy humans from the insulin infusion required to maintain an 8 mmol/l glucose concentration during hyperglycemic pancreatic clamp with or without infusion of 16.7 micromol. kg(-1). min(-1) fructose. Glucose rate of disappearance (GR(d)), net endogenous glucose production (NEGP), total glucose output (TGO), and glucose cycling (GC) were measured with [6,6-(2)H(2)]- and [2-(2)H(1)]glucose. Hepatic glycogen synthesis was estimated from uridine diphosphoglucose (UDPG) kinetics as assessed with [1-(13)C]galactose and acetaminophen. Fructose infusion increased insulin requirements 2.3-fold to maintain blood glucose. Fructose infusion doubled UDPG turnover, but there was no effect on TGO, GC, NEGP, or GR(d) under hyperglycemic pancreatic clamp protocol conditions. When insulin concentrations were matched during a second hyperglycemic pancreatic clamp protocol, fructose administration was associated with an 11.1 micromol. kg(-1). min(-1) increase in TGO, a 7.8 micromol. kg(-1). min(-1) increase in NEGP, a 2.2 micromol. kg(-1). min(-1) increase in GC, and a 7.2 micromol. kg(-1). min(-1) decrease in GR(d) (P < 0. 05). These results indicate that fructose infusion induces hepatic and extrahepatic insulin resistance in humans.

High protein intake reduces intrahepatocellular lipid deposition in humans.

BACKGROUND: High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown. OBJECTIVE: The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men. DESIGN: Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens. RESULTS: The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14). CONCLUSIONS: Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.

Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study.

BACKGROUND: We aimed to assess the value of a structured clinical assessment and genetic testing for refining the diagnosis of abacavir hypersensitivity reactions (ABC-HSRs) in a routine clinical setting. METHODS: We performed a diagnostic reassessment using a structured patient chart review in individuals who had stopped ABC because of suspected HSR. Two HIV physicians blinded to the human leukocyte antigen (HLA) typing results independently classified these individuals on a scale between 3 (ABC-HSR highly likely) and -3 (ABC-HSR highly unlikely). Scoring was based on symptoms, onset of symptoms and comedication use. Patients were classified as clinically likely (mean score > or =2), uncertain (mean score > or = -1 and < or = 1) and unlikely (mean score < or = -2). HLA typing was performed using sequence-based methods. RESULTS: From 131 reassessed individuals, 27 (21%) were classified as likely, 43 (33%) as unlikely and 61 (47%) as uncertain ABC-HSR. Of the 131 individuals with suspected ABC-HSR, 31% were HLA-B*5701-positive compared with 1% of 140 ABC-tolerant controls (P < 0.001). HLA-B*5701 carriage rate was higher in individuals with likely ABC-HSR compared with those with uncertain or unlikely ABC-HSR (78%, 30% and 5%, respectively, P < 0.001). Only six (7%) HLA-B*5701-negative individuals were classified as likely HSR after reassessment. CONCLUSIONS: HLA-B*5701 carriage is highly predictive of clinically diagnosed ABC-HSR. The high proportion of HLA-B*5701-negative individuals with minor symptoms among individuals with suspected HSR indicates overdiagnosis of ABC-HSR in the era preceding genetic screening. A structured clinical assessment and genetic testing could reduce the rate of inappropriate ABC discontinuation and identify individuals at high risk for ABC-HSR.

Kinetics of dexamethasone-induced alterations of glucose metabolism in healthy humans.

Six healthy human subjects were studied during three 75-g oral, [13C]glucose tolerance tests to assess the kinetics of dexamethasone-induced impairment of glucose tolerance. On one occasion, they received dexamethasone (4 x 0.5 mg/day) during the previous 2 days. On another occasion, they received a single dose (0. 5 mg) of dexamethasone 150 min before ingestion of the glucose load. On the third occasion, they received a placebo. Postload plasma glucose was significantly increased after both 2 days dexamethasone and single dose dexamethasone compared with control (P < 0.05). This corresponded to a 20-23% decrease in the metabolic clearance rate of glucose, whereas total glucose turnover ([6,6-2H]glucose), total (indirect calorimetry) and exogenous glucose oxidation (13CO2 production), and suppression of endogenous glucose production were unaffected by dexamethasone. Plasma insulin concentrations were increased after 2 days of dexamethasone but not after a single dose of dexamethasone. In a second set of experiments, the effect of a single dose of dexamethasone on insulin sensitivity was assessed in six healthy humans during a 2-h euglycemic hyperinsulinemic clamp. Dexamethasone did not significantly alter insulin sensitivity. It is concluded that acute administration of dexamethasone impairs oral glucose tolerance without significantly decreasing insulin sensitivity.

Les règles n'ont plus la cote: une question de contraception ou de choix [To bleed or not--a new dogma or a real choice in contraception?]

On en parle ! Il est question de la suppression des règles par l'administration de contraceptifs oestro-progestatifs (pilule, patch ou anneau vaginal) en cycles longs (cycles prolongés ; cycles étendus ; extended cycles) entraînant des périodes d'aménorrhée, rythmées par des intervalles libres de sept jours sans administration hormonale. L'indication à ce mode de prescription est presque unanimement reconnue pour le traitement des pathologies bénéficiant de la suppression des règles et des fluctuations hormonales inhérentes à l'activité ovarienne. Ce traitement suscite cependant également de l'intérêt pour une indication du type mode de vie. Les modalités thérapeutiques, les avantages et inconvénients sont examinés à la lumière de l'attente des femmes et de leur droit au choix éclairé et libre. Let's talk about it ! Suppression of menstruation, by extending the duration of contraceptives containing estro-progestins (oral contraception, patch or vaginal ring) to long cycles, is a new approach in the field of contraception. These extended cycles aim at obtaining prolonged amenorrhea, interrupted periodically by a free interval of 7 days without hormone intake and thus causing breakthrough bleeding. Pathologies, which are supposed to get some benefit from the suppression of menstruation and of hormone level variations related to ovarian activity, are widely recognized as an indication. Some interest is also coming up for so called life style indications. Treatment issues, advantages and disadvantages are examined in the light of women's expectations and right to access to informed consent and independent choice.

How to measure cortical folding from MR images: a step-by-step tutorial to compute local gyrification index.

Cortical folding (gyrification) is determined during the first months of life, so that adverse events occurring during this period leave traces that will be identifiable at any age. As recently reviewed by Mangin and colleagues(2), several methods exist to quantify different characteristics of gyrification. For instance, sulcal morphometry can be used to measure shape descriptors such as the depth, length or indices of inter-hemispheric asymmetry(3). These geometrical properties have the advantage of being easy to interpret. However, sulcal morphometry tightly relies on the accurate identification of a given set of sulci and hence provides a fragmented description of gyrification. A more fine-grained quantification of gyrification can be achieved with curvature-based measurements, where smoothed absolute mean curvature is typically computed at thousands of points over the cortical surface(4). The curvature is however not straightforward to comprehend, as it remains unclear if there is any direct relationship between the curvedness and a biologically meaningful correlate such as cortical volume or surface. To address the diverse issues raised by the measurement of cortical folding, we previously developed an algorithm to quantify local gyrification with an exquisite spatial resolution and of simple interpretation. Our method is inspired of the Gyrification Index(5), a method originally used in comparative neuroanatomy to evaluate the cortical folding differences across species. In our implementation, which we name local Gyrification Index (lGI(1)), we measure the amount of cortex buried within the sulcal folds as compared with the amount of visible cortex in circular regions of interest. Given that the cortex grows primarily through radial expansion(6), our method was specifically designed to identify early defects of cortical development. In this article, we detail the computation of local Gyrification Index, which is now freely distributed as a part of the FreeSurfer Software (http://surfer.nmr.mgh.harvard.edu/, Martinos Center for Biomedical Imaging, Massachusetts General Hospital). FreeSurfer provides a set of automated reconstruction tools of the brain's cortical surface from structural MRI data. The cortical surface extracted in the native space of the images with sub-millimeter accuracy is then further used for the creation of an outer surface, which will serve as a basis for the lGI calculation. A circular region of interest is then delineated on the outer surface, and its corresponding region of interest on the cortical surface is identified using a matching algorithm as described in our validation study(1). This process is repeatedly iterated with largely overlapping regions of interest, resulting in cortical maps of gyrification for subsequent statistical comparisons (Fig. 1). Of note, another measurement of local gyrification with a similar inspiration was proposed by Toro and colleagues(7), where the folding index at each point is computed as the ratio of the cortical area contained in a sphere divided by the area of a disc with the same radius. The two implementations differ in that the one by Toro et al. is based on Euclidian distances and thus considers discontinuous patches of cortical area, whereas ours uses a strict geodesic algorithm and include only the continuous patch of cortical area opening at the brain surface in a circular region of interest.

Thermogenesis and fructose metabolism in humans.

Resting metabolic rate was measured in 10 healthy volunteers (25 yr, 73 kg, 182 cm) for 1 h before and 4 h during intravenous (iv) fructose administration (20% at 50 mumol.kg-1.min-1) with (+P) or without (-P) propranolol (100 micrograms/kg, 1 microgram.kg-1.min-1) during the last 2 h. Some subjects were studied a further 2 h with fructose infusion and +P or -P in hyperinsulinemic (2.9 pmol.kg-1.min-1) euglycemic conditions. Glucose turnover ([3-3H]glucose, 20 muCi bolus and 0.2 muCi/min) was calculated over 30 min at 0, 2, 4, and 6 h. The thermic effect of iv fructose was approximately 7.5% and decreased to 4.9 +/- 0.4% (P less than 0.01) +P. During the euglycemic clamp the thermic effect was 6.2 +/- 0.9% (-P) and 5.3 +/- 0.9% (+P). Hepatic glucose production (HGP) was 11.7 mumol.kg-1.min-1 (0 h) and did not change after 2 h iv fructose (11.8 +/- 0.5 and 9.8 +/- 0.6 mumol.kg-1.min-1 -P and +P, respectively) but increased to 13.8 +/- 0.9 (-P) and 12.9 +/- 0.8 mumol.kg-1.min-1 (+P) (P less than 0.01) after 4 h. HGP was suppressed to varying degrees during the euglycemic clamp. It is concluded that 1) the greater thermic effect of fructose compared with glucose is probably due to continued gluconeogenesis (which is suppressed by glucose or glucose-insulin) and the energy cost of fructose metabolism to glucose in the liver. 2) There is a sympathetically mediated component to the thermic effect of fructose (approximately 30%) that is not mediated by elevated plasma insulin concentrations similar to those observed with iv glucose.

Adaptive diversity in heterogeneous environments for populations regulated by a mixture of soft and hard selection

The stable co-existence of two haploid genotypes or two species is studied in a spatially heterogeneous environment submitted to a mixture of soft selection (within-patch regulation) and hard selection (outside-patch regulation) and where two kinds of resource are available. This is analysed both at an ecological time-scale (short term) and at an evolutionary time-scale (long term). At an ecological scale, we show that co-existence is very unlikely if the two competitors are symmetrical specialists exploiting different resources. In this case, the most favourable conditions are met when the two resources are equally available, a situation that should favour generalists at an evolutionary scale. Alternatively, low within-patch density dependence (soft selection) enhances the co-existence between two slightly different specialists of the most available resource. This results from the opposing forces that are acting in hard and soft regulation modes. In the case of unbalanced accessibility to the two resources, hard selection favours the most specialized genotype, whereas soft selection strongly favours the less specialized one. Our results suggest that competition for different resources may be difficult to demonstrate in the wild even when it is a key factor in the maintenance of adaptive diversity. At an evolutionary scale, a monomorphic invasive evolutionarily stable strategy (ESS) always exists. When a linear trade-off exists between survival in one habitat versus that in another, this ESS lies between an absolute adjustment of survival to niche size (for mainly soft-regulated populations) and absolute survival (specialization) in a single niche (for mainly hard-regulated populations). This suggests that environments in agreement with the assumptions of such models should lead to an absence of adaptive variation in the long term.