Steady-state equilibrium phase inversion recovery ON-resonant water suppression (IRON) MR angiography in conjunction with superparamagnetic nanoparticles. A robust technique for imaging within a wide range of contrast agent dosages.

PURPOSE: To investigate the ability of inversion recovery ON-resonant water suppression (IRON) in conjunction with P904 (superparamagnetic nanoparticles which consisting of a maghemite core coated with a low-molecular-weight amino-alcohol derivative of glucose) to perform steady-state equilibrium phase MR angiography (MRA) over a wide dose range. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. Rabbits (n = 12) were imaged at baseline and serially after the administration of 10 incremental dosages of 0.57-5.7 mgFe/Kg P904. Conventional T1-weighted and IRON MRA were obtained on a clinical 1.5 Tesla (T) scanner to image the thoracic and abdominal aorta, and peripheral vessels. Contrast-to-noise ratios (CNR) and vessel sharpness were quantified. RESULTS: Using IRON MRA, CNR and vessel sharpness progressively increased with incremental dosages of the contrast agent P904, exhibiting constantly higher contrast values than T1 -weighted MRA over a very wide range of contrast agent doses (CNR of 18.8 ± 5.6 for IRON versus 11.1 ± 2.8 for T1 -weighted MRA at 1.71 mgFe/kg, P = 0.02 and 19.8 ± 5.9 for IRON versus -0.8 ± 1.4 for T1-weighted MRA at 3.99 mgFe/kg, P = 0.0002). Similar results were obtained for vessel sharpness in peripheral vessels, (Vessel sharpness of 46.76 ± 6.48% for IRON versus 33.20 ± 3.53% for T1-weighted MRA at 1.71 mgFe/Kg, P = 0.002, and of 48.66 ± 5.50% for IRON versus 19.00 ± 7.41% for T1-weighted MRA at 3.99 mgFe/Kg, P = 0.003). CONCLUSION: Our study suggests that quantitative CNR and vessel sharpness after the injection of P904 are consistently higher for IRON MRA when compared with conventional T1-weighted MRA. These findings apply for a wide range of contrast agent dosages.

Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps

Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps Darbellay Bastien Institut de Minéralogie et Géochimie Résumé grand public Comme toute matière, la roche est sensible à son environnement et cherche à s'adapter pour acquérir un état stable (état d'équilibre). Les changements des conditions physiques (température et pression) vont ainsi impliquer des modifications dans la roche. Le métamorphisme est l'étude de ces changements. Les minéraux qui constituent la roche peuvent modifier, leur structure, leur chimie ou être remplacer par d'autres minéraux plus stables. Il est ainsi crucial de déterminer les processus responsables et limitant de la croissance minérale. Trois processus permettent la croissance ; (1) la dissolution des éléments du réactant, (2) le transport de ces éléments vers le site de croissance, (3) l'incorporation de ces éléments dans la nouvelle structure. Cette thèse se focalise sur les structures des minéraux de haute pression (forme, zonation chimique, structure interne) pour essayer de déterminer les facteurs importants à l'origine de leur état final. Les zones d'étude se situent dans la zone de Sésia. La première partie traite de la problématique liée à l'incorporation d'un élément dans une structure minérale. A l'image de la croissance humaine, les irrégularités minéralogiques permettent de mettre en lumière un dysfonctionnement de la croissance due à un excès ou à une carence d'un élément. Bien dosé, cet élément est cependant essentiel à la croissance. Les zoisites (épidotes) des métabasites de la région de Cima di Bonze montrent une zonation chimique en sablier. Dans cette zonation la teneur en fer excède la capacité maximum que peut contenir la structure orthorhombique de la zoisite. Des défauts de structure permettent l'accommodation de cet excès. La zoisite peut ainsi adapter sa structure pour permettre l'incorporation d'une relativement grande quantité de fer. Les études précédentes montraient, pour des conditions similaires, la formation de deux épidotes distinctes. La deuxième partie se penche sur la compétition entre le minéral qui fait sa croissance et les minéraux (réactants) qui l'entourent. Les métapélites de la région du Monte Mucrone contiennent des grenats atollaires. Des études détaillées de la texture et de la zonation chimique du grenat ainsi qu'une modélisation thermodynamique ont permis de mieux cerner les facteurs importants responsables de la forme atollaire. Cette structure est obtenue par un changement du comportement de la croissance du grenat le long d'un chemin P-T hercynien. Dans un premier stade, le grenat croît rapidement et consume peu le quartz de la matrice. La croissance se fait ainsi le long des jointures des grains de quartz. Dans un second temps, les changements de conditions PT donnent une croissance lente du grenat et une forte consommation du quartz. Le grenat peut ainsi développer sa forme dodécaédrale classique. La troisième partie s'intéresse aux distances de transport par diffusion d'un élément (ici l'argon) durant la haute pression. Pour ce faire, un profile d'âges 40Ar/39Ar sur biotite a été mesuré depuis un veine de haute pression riche en argon jusque dans son encaissant (granitoïd du Monte Mucrone). Le profile montre une répartition des âges suivant une courbe de diffusion. Le transport se fait sur une longueur de deux centimètre avec l'aide d'un fluide. Il est réduit à une échelle millimétrique quand la phase fluide disparaît. Cette étude montre ainsi les difficultés de transport des éléments durant la haute pression ne permettant pas un rééquilibrage de la roche à grande échelle. Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps Darbellay Bastien Institut de Minéralogie et Géochimie Résumé de thèse Les processus de croissance (diffusion des éléments et les réactions d'interface) et les conditions dans lesquelles les minéraux grandissent (température, pression, fluide, composition chimique de la roche), déterminent la texture ainsi que la zonation des minéraux. Cette thèse se focalise, par le biais de textures peu communes, sur trois différents processus impliqués dans la croissance minérale à haute pression (Zone de Sésia, Alpes de l'Ouest, Italie). L'incorporation d'un élément dans une structure minérale ne peut se faire que dans des sites en accord avec la taille et la charge ionique de l'élément. De plus, la balance de charge doit être maintenue dans le minéral. La régularité de la structure cristalline fixe ainsi une limite maximum de concentration d'un élément donné. Les zoisites provenant des métabasites de la région de Cima di Bonze montrent des zonations en sablier caractérisées par une concentration anormale en fer. La zonation se marque par une différente teinte de biréfringence et par un plus grand angle d'extinction que le reste de la zoisite. Une inter-croissance de clinozoisite à l'intérieur de la structure orthorhombique de la zoisite peut ainsi être suspectée. Les analyses XRD (diffraction des rayons x) ainsi que les analyses Raman ne confirment pas cette suspicion. Seules les analyses TEM (microscope à électrons transmis) montrent des défauts de structure pouvant être interprétés comme des modules de clinozoisite. Ils ne peuvent cependant pas être considérés comme une phase thermodynamique. Un nouveau trou d'immiscibilité entre deux zoisite (X ep= 0.1 and Xep = 0.15) a ainsi pu être établi. Dans les métapélites la région du Monte Mucrone, des grenats fortement zonés montrent une évolution texturale singulière. Ils présentent une forme initiale de `champignon' qui se développe pour former une structure atollaire finale. L'étude conjuguée de la structure 3D et des zonations, ainsi que l'établissement d'un model thermodynamique, indiquent que ces structures proviennent de deux épisodes de croissances : (1) La croissance du grenat durant un chemin prograde hercynien (de 525 °C et 6.2 kbar à 640 °C et 9 kbar) permet la formation des textures atollaires. Elles sont le résultat d'une croissance poecilitique initiale suivie d'une croissance idiomorphique du grenat. (2) La structure est rendue plus complexe par la cristallisation d'un grenat homogène tout autour ainsi qu'à l'intérieur du grenat hercynien durant la haute pression alpine (550 °C and 20 kbar). L'arrivée de l'eau durant la haute pression facilite le transport d'éléments et permet une cristallisation rapide du grenat. La diffusion peut être un facteur limitant de la croissance minéralogique. Elle a aussi une grande importance pour la géochronologie. Une veine de haute pression à l'intérieur du granitoïde du Monte Mucrone a été étudiée dans le but de déterminer la distance de diffusion de l'argon. Le profile d'âges 40Ar/39Ar sur biotites, établi de la veine vers le métagranitoïde, suit une courbe de diffusion. Les âges sont élevés proche de la veine (800 Ma) puis décroissent jusqu'à des âges homogènes (170-150 Ma) à deux centimètres de la veine. La présence de fluide, marqué par de hautes concentrations en chlore, permet une diffusion centimétrique. Cependant, la distance est réduite à une échelle millimétrique quand le fluide est absent. Les très faibles distances de diffusion préservent les âges pré-alpins et impliquent un événement géologique pour les âges de 170-150 Ma. Kinetics of crystal growth and equilibrium domains in eclogite of the Sesia Zone, Western Alps Darbellay Bastien Institut de Minéralogie et Géochimie Thesis abstract Rock textures and zonings are the consequence of growth processes (element diffusion and interface reaction) steered by the environment in which they grew (pressure, differential stress, temperature, fluid and rock composition). The thesis presented here focuses on three different topics, each of it dealing with aspects of mineral growth processes during subduction, in a high-pressure environment. All studies were conducted in the Sesia Zone of the Western European Alps, Italy. The first study addresses the crystallography and geochemistry of element incorporation in zoisite, one of the major hydrous minerals found in subduction zone rocks. Elements can be incorporated into a mineral structure only on crystallographic sites that offer enough space for the ion and the overall charge balance has to be maintained. Element concentrations are hence limited. Incorporation of some elements produces complex zoning, including hourglass like patterns, which are the focus of the first contribution. Zoisites from Cima di Bonze (Sesia Zone) show spectacular hourglass zoning defined by Fe-content variations. The hourglass zones have a distinct birefringence and a different extinction angle than the regular part of the zoisite. We show by detailed XRD (X-ray diffraction) and confocal Raman analyses that the high Fe-zones are nevertheless zoisite, and not clinozoisite as one might expect. High resolution TEM (transmission electron microscopy) analyses show planar defects on (100) that can be interpreted as small-scale clinozoisite modules. However, these clinozoisites cannot be interpreted as a distinctive thermodynamic phase and the entire mineral has to be considered as zoisite. The miscibility gap between two zoisites (Xep = 0.1 and Xep = 0.15) can be then definite at 550 ± 50°C and 14 to 20 Kbar. Strongly zoned garnets in quartz rich metapelite from the Monte Mucrone area (Sesia Zone) show evolution form 3D mushroom to atoll structure. The second contribution presents textural investigations, garnet zoning and thermodynamic modeling that demonstrate that atoll garnets are the result of two distinctive growth events. (1) Garnet atoll structure is already formed during a prograde Hercynian path from 525 °C and 6.2 kbar to 640 °C and 9 kbar. It results in an initial poikilitic growth followed by a final idiomorphic growth event. (2) Alpine HP garnet are homogenous (550 °C and 20 kbar) and grew around and also inside the Hercynian garnet. Lack of prograde Alpine garnet and fast growth of the HP garnet is explained by the absence of water during much of the prograde path. Water saturation was only observed towards the end, close towards the peak metamorphic conditions. Diffusion could be a limiting factor for crystal growth. It has also a great importance in geochronology. HP vein inside the metagranitoide of the Monte Mucrone (~300 Ma) was investigated to determine argon diffusion scales during high-pressure metamorphism. 40Ar/39Ar biotite ages profile from the vein toward the metagranodiorite show a diffusion curve: old ages (800 Ma) located close to the vein decrease until homogenous 170-150 Ma ages are obtained, two centimeter away from the vein. Centimeter-scale diffusion occurs with help of a fluid phase marked by high chlorine concentrations. Argon diffusion is reduced to a millimeter scale when free fluid is absent. Very short diffusion distance permits to preserve pre-Alpine ages. The 170-150 Ma ages are considered to be geologic meaningful, probably resulting from the extensional tectonics linked to opening of the Tethian ocean.

Stable isotope geochemistry and phase-equilibria of coesite-bearing whiteschists, Dora Maira massif, Western Alps

Peak metamorphic temperatures for the coesite-pyrope-bearing whiteschists from the Dora Maira Massif, western Alps were determined with oxygen isotope thermometry. The deltaO-18(SMOW) values of the quartz (after coesite) (delta O-18 = 8.1 to 8.6 parts per thousand, n = 6), phengite (6.2 to 6.4 parts per thousand, n = 3), kyanite (6.1 parts per thousand, n = 2), garnet (5.5 to 5.8 parts per thousand, n = 9), ellenbergerite (6.3 parts per thousand, n = 1) and rutile (3.3. to 3.6 parts per thousand, n = 3) reflect isotopic equilibrium. Temperature estimates based on quartz-garnet-rutile fractionation are 700-750-degrees-C. Minimum pressures are 31-32 kb based on the pressure-sensitive reaction pyrope + coesite = kyanite + enstatite. In order to stabilize pyrope and coesite by the temperature-sensitive dehydration reaction talc + kyanite = pyrope + coesite + H2O, the a(H2O) must be reduced to 0.4-0.75 at 700 750-degrees-C. The reduced a(H2O) cannot be due to dilution by CO2, as pyrope is not stable at X (CO2) > 0.02 (T = 750-degrees-C; P = 30 kb). In the absence of a more exotic fluid diluent (e.g. CH4 or N2), a melt phase is required. Granite solidus temperatures are approximately 680-degrees-C/30 kb at a(H2O) = 1.0 and are calculated to be approximately 70-degrees-C higher at a(H2O) = 0.7, consistent with this hypothesis. Kyanite-jadeite-quartz bands may represent a relict melt phase. Peak P-T-f(H2O) estimates for the whiteschist are 34 +/- 2 kb, 700-750-degrees-C and 0.4-0.75. The oxygen isotope fractionation between quartz (deltaO-18 = 11.6%.) and garnet (deltaO-18 = 8.7 parts per thousand) in the surrounding orthognesiss is identical to that in the coesite-bearing unit, suggesting that the two units shared a common, final metamorphic history. Hydrogen isotope measurements were made on primary talc and phengite (deltaD(smow) = -27 to -32 parts per thousand), on secondary talc and chlorite after pyrope (deltaD = - 39 to - 44 parts per thousand) and on the surrounding biotite (deltaD = -64 parts per thousand) and phengite (deltaD = -44 parts per thousand) gneiss. All phases appear to be in near-equilibrium. The very high deltaD values for the primary hydrous phases is consistent with an initial oceanic-derived/connate fluid source. The fluid source for the retrograde talc + chlorite after pyrope may be fluids evolved locally during retrograde melt crystallization. The similar deltaD, but dissimilar deltaO-18 values of the coesite-bearing whiteschists and hosting orthogneiss suggest that the two were in hydrogen isotope equilibrium, but not oxygen isotope equilibrium. The unusual hydrogen and oxygen isotope compositions of the coesite-bearing unit can be explained as the result of metasomatism from slab-derived fluids at depth.

Quantification of magmatic and hydrothermal processes in a peralkaline syenite-alkali granite complex based on textures, phase equilibria, and stable and radiogenic isotopes

The Puklen complex of the Mid-Proterozoic Gardar Province, South Greenland, consists of various silica-saturated to quartz-bearing syenites, which are intruded by a peralkaline granite. The primary mafic minerals in the syenites are augite +/- olivine + Fe-Ti oxide + amphibole. Ternary feldspar thermometry and phase equilibria among mafic silicates yield T = 950-750degreesC, a(SiO2) = 0.7-1 and an f(O2) of 1-3 log units below the fayalite-magnetite-quartz (FMQ) buffer at 1 kbar. In the granites, the primary mafic minerals are ilmenite and Li-bearing arfvedsonite, which crystallized at temperatures below 750degreesC and at f(O2) values around the FMQ buffer. In both rock types, a secondary post-magmatic assemblage overprints the primary magmatic phases. In syenites, primary Ca-bearing minerals are replaced by Na-rich minerals such as aegirine-augite and albite, resulting in the release of Ca. Accordingly, secondary minerals include ferro-actinolite, (calcite-siderite)(ss), titanite and andradite in equilibrium with the Na-rich minerals. Phase equilibria indicate that formation of these minerals took place over a long temperature interval from near-magmatic temperatures down to similar to300degreesC. In the course of this cooling, oxygen fugacity rose in most samples. For example, late-stage aegirine in granites formed at the expense of arfvedsonite at temperatures below 300degreesC and at an oxygen fugacity above the haematite-magnetite (HM) buffer. The calculated delta(18)O(melt) value for the syenites (+5.9 to +6.3parts per thousand) implies a mantle origin, whereas the inferred delta(18)O(melt) value of <+5.1parts per thousand for the granitic melts is significantly lower. Thus, the granites require an additional low-delta(18)O contaminant, which was not involved in the genesis of the syenites. Rb/Sr data for minerals of both rock types indicate open-system behaviour for Rb and Sr during post-magmatic metasomatism. Neodymium isotope compositions (epsilonNd(1170 Ma) = -3.8 to -6.4) of primary minerals in syenites are highly variable, and suggest that assimilation of crustal rocks occurred to variable extents. Homogeneous epsilon(Nd) values of -5.9 and -6.0 for magmatic amphibole in the granites lie within the range of the syenites. Because of the very similar neodymium isotopic compositions of magmatic and late- to post-magmatic minerals from the same syenite samples a principally closed-system behaviour during cooling is implied. In contrast, for the granites an externally derived fluid phase is required to explain the extremely low epsilon(Nd) values of about -10 and low delta(18)O between +2.0 and +0.5parts per thousand for late-stage aegirine, indicating an open system in the late-stage history. In this study we show that the combination of phase equilibria constraints with stable and radiogenic isotope data on mineral separates can provide much better constraints on magma evolution during emplacement and crystallization than conventional whole-rock studies.

Epidote in hydrous mafic magmas : near solidus phase relations in the lower crust

Crystallisation of hydrous mafic magmas at high pressure is a subject of numerous petrologic and experimental studies since the last century and is mainly related to the process of continental crust formation and the possible link between mantle derived melts and low pressure granitoids. Albeit the sequence of crystallization is well constrained by experimental studies, the origin of exposed lower crustal rocks exposed on the earth surface is controversial. Ones line of argument is favouring high pressure crystallization of dry or wet mafic magmas, whereas others invoke partial melting of pre-existing crust. Therefore studies involving field, textural and chemical observations of exposed lower crust such as in Kohistan (Pakistan) or Talkeetna (Alaska) are crucial to understand the continental crust formation processes via arc magmatism. Epidote-bearing gabbros are very sparse and always associated with the deep part of continental crust (>30 km) as in the Kohistan Arc Complex (Pakistan) or in the Chelan Complex (western U.S.). Magmatic epidote is restricted to a small temperature interval above the water-saturated solidus of MORB and represent the last crystallizing liquids in lower crustal regions. However, epidote and melt stability at lower crustal pressures are not clearly established.¦The Chelan complex (western U.S.) at the base of the Cascadian Arc is composed mainly by peraluminous tonalité associated with gabbroic and ultramafic rocks and was traditionally interpreted as a migmatitic terrain. However field, chemical and mineralogical observations rather suggest a magmatic origin and point to a protracted crystallization at intermediate to high pressure ~ 1.0 GPa dominated by amphibole fractionation and followed by isobaric cooling down to 650°C. Crystal fractionation modelling using whole rock composition and field constraints is able to generate peraluminous tonalité. The modelled crystallisation sequence and the volume proportions are in agreement with experimental studies performed at these pressures. The Chelan complex was thus not formed during a partial melting event, but represent the sequence of crystallisation occurring at the base of the crust. Massive fractionation of hornblende is able to generate peraluminous tonalité without significant assimilation of crustal rock.¦Similarly to the Chelan complex, the base of the Kohistan arc is composed of cumulates derived by high pressure crystallization of hydrous magma. In garnet gabbros, epidote occurs as magmatic phase, crystallising from hydrous interstitial melt trapped between grain boundaries at lower crustal pressures (Ρ ~ 1.2 GPa) for temperature of (650-700 °C). Trace and REE signature in epidote indicate that epidote was formed through peritectic reaction involving garnet, clinopyroxene and plagioclase. At the beginning of the crystallisation epidote signature is dominated by REE content in the melt, whereas at the end the signature is dominated by reacting phases. Melt in equilibrium with epidote inferred from the partition coefficients available is similar to intrusive tonalité up the section indicating that hydrous melt was extracted from the garnet gabbros. In some gabbros epidote shows single homogeneous compositions, while in others coexisting epidote have different compositions indicating the presence of solvi along the Al-Fe3+ join. The overgowths are only observed in presence of paragonite in the assemblage, suggesting high water content. At high water content, the hydrous solidus is shift to lower temperature and probably intersects the solvi observed along the Al-Fe3+ join. Therefore, several compositions of epidote is stable at high water content.¦-¦La composition chimique de la croûte continentale est considérée comme similaire à celle du magmatisme calco-alcalin de marge continentale active (enrichissement en éléments mobiles dans les fluides, anomalies négatives en Nb, Ta et éléments à haut potentiel électronique, etc...). Cependant la nature andésitique de la croûte continentale (Si02 > 60 wt%), résultant des nombreuses intrusions de granitoïdes dans la croûte supérieure, est sujette à polémique et le lien entre les magmas dérivés du manteau et les roches évoluées de faible profondeur n'est pas clairement établi (fusion partielle de croûte basaltique, cristallisation fractionnée à haute pression, etc...).¦Les affleurements de croûte profonde sont rares mais précieux, car ils permettent d'observer les phénomènes se passant à grande profondeur. Le complexe de Chelan (Washington Cascades) en est un exemple. Formé à environ 30 km de profondeur, il est composé de roches gabbroïques et ultramafiques, ainsi que de tonalités, qui furent souvent interprétés comme le produit de la fusion partielle de la croûte. Cependant, les relations de terrain, la chimie des éléments majeurs et des éléments traces sont cohérentes avec l'évolution d'un complexe magmatique mafique dans la croûte profonde ou moyenne ( 1.0 GPa), dominée par le fractionnement de l'amphibole. Après son emplacement, le complexe a subi un refroidissement isobare jusqu'à des températures de l'ordre de 650 °C, déduit de la composition chimique des minéraux. Un bilan de masse contraint pax les observations de terrain permet de calculer la séquence et les volumes de fractionnement. Les faciès évolués légèrement hyperalumineux observés sur le terrain peuvent être générés par la cristallisation de 3 % de websterite à olivine, 12 % d'hornblendite à pyroxène 33 % d'hornblendite, 19 % de gabbros, 15 % de diorite et 2 % de tonalité. Nous montrons ainsi qu'une série de fractionnement contrôlée par l'amphibole permet de générer des tonalités sans assimilation de matériel crustal et l'exemple de Chelan illustre la viabilité de ce processus dans la formation de croûte continentale.¦Les réactions proches du solidus saturé en H20 dans les systèmes basaltiques à des pressions élevées restent énigmatiques. Diverses expériences tendent à montrer que l'épidote est stable dans ces conditions, mais rarement observée (décrite ?) comme phase primaire dans les systèmes naturels. Les épidotes trouvées dans les gabbros de Jijal (nord-Pakistan) montrent des textures de type .magmatique telles qu'observées dans les roches évoluées. Le contenu en terres rares de ces épidotes est très variable allant de signatures enrichies en terres rares légères impliquant la présence de liquide interstitiel à des signatures complètement déprimées en ces mêmes éléments, évoquant une cristallisation en coexistence avec du grenat. Ces diverses signatures reflètent un chemin de cristallisation en présence de liquide interstitiel et enregistrent des réactions péritectiques impliquant grenat, clinopyroxene et plagioclase à des pressions de ~ 1.2 GPa pour des températures de 650-700 °C. Cependant dans quelques échantillons deux ou trois compositions d'épidotes coexistent démontrant la présence de lacunes d'immiscibilité le long de la solution solide épidote-clinozoïsite. La forte teneur en H20 du liquide magmatique est certainement à l'origine de la coexistence de deux compositions distinctes.

Decreased thermal conductance during the luteal phase of the menstrual cycle in women.

To study the influence of the menstrual cycle on whole body thermal balance and on thermoregulatory mechanisms, metabolic heat production (M) was measured by indirect calorimetry and total heat losses (H) were measured by direct calorimetry in nine women during the follicular (F) and the luteal (L) phases of the menstrual cycle. The subjects were studied while exposed for 90 min to neutral environmental conditions (ambient temperature 28 degrees C, relative humidity 40%) in a direct calorimeter. The values of M and H were not modified by the phase of the menstrual cycle. Furthermore, in both phases the subjects were in thermal equilibrium because M was similar to H (69.7 +/- 1.8 and 72.1 +/- 1.8 W in F and 70.4 +/- 1.9 and 71.4 +/- 1.7 W in L phases, respectively). Tympanic temperature (Tty) was 0.24 +/- 0.07 degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. Calculated skin thermal conductance (Ksk) was lower in the L (17.9 +/- 0.6 W.m-2.degrees C-1) than in the F phase (20.1 +/- 1.1 W.m-2.degrees C-1; P less than 0.05). Calculated skin blood flow (Fsk) was also lower in the L (0.101 +/- 0.008 l.min-1.m-2) than in the F phase (0.131 +/- 0.015 l.min-1.m-2; P less than 0.05). Differences in Tty, Ksk, and Fsk were not correlated with changes in plasma progesterone concentration. It is concluded that, during the L phase, a decreased thermal conductance in women exposed to a neutral environment allows the maintenance of a higher internal temperature.

Wireless GPS-based phase-locked synchronization system for outdoor environment.

Synchronization of data coming from different sources is of high importance in biomechanics to ensure reliable analyses. This synchronization can either be performed through hardware to obtain perfect matching of data, or post-processed digitally. Hardware synchronization can be achieved using trigger cables connecting different devices in many situations; however, this is often impractical, and sometimes impossible in outdoors situations. The aim of this paper is to describe a wireless system for outdoor use, allowing synchronization of different types of - potentially embedded and moving - devices. In this system, each synchronization device is composed of: (i) a GPS receiver (used as time reference), (ii) a radio transmitter, and (iii) a microcontroller. These components are used to provide synchronized trigger signals at the desired frequency to the measurement device connected. The synchronization devices communicate wirelessly, are very lightweight, battery-operated and thus very easy to set up. They are adaptable to every measurement device equipped with either trigger input or recording channel. The accuracy of the system was validated using an oscilloscope. The mean synchronization error was found to be 0.39 μs and pulses are generated with an accuracy of <2 μs. The system provides synchronization accuracy about two orders of magnitude better than commonly used post-processing methods, and does not suffer from any drift in trigger generation.

Multi-phase post-mortem CT angiography: development of a standardized protocol.

The objective of this work was to develop an easily applicable technique and a standardized protocol for high-quality post-mortem angiography. This protocol should (1) increase the radiological interpretation by decreasing artifacts due to the perfusion and by reaching a complete filling of the vascular system and (2) ease and standardize the execution of the examination. To this aim, 45 human corpses were investigated by post-mortem computed tomography (CT) angiography using different perfusion protocols, a modified heart-lung machine and a new contrast agent mixture, specifically developed for post-mortem investigations. The quality of the CT angiographies was evaluated radiologically by observing the filling of the vascular system and assessing the interpretability of the resulting images and by comparing radiological diagnoses to conventional autopsy conclusions. Post-mortem angiography yielded satisfactory results provided that the volumes of the injected contrast agent mixture were high enough to completely fill the vascular system. In order to avoid artifacts due to the post-mortem perfusion, a minimum of three angiographic phases and one native scan had to be performed. These findings were taken into account to develop a protocol for quality post-mortem CT angiography that minimizes the risk of radiological misinterpretation. The proposed protocol is easy applicable in a standardized way and yields high-quality radiologically interpretable visualization of the vascular system in post-mortem investigations.

Intervention précoce dans la phase initiale des troubles psychotiques à Lausanne: quels problèmes et quelles solutions [Early intervention for the initial phase of psychotic disorders in Lausanne: what problems and what solutions?]

Schizophrenia has long been considered with pessimism, but the recent interest in the early phase of psychotic disorders has modified this often unjustified perception. Literature has demonstrated the benefit of the development of programs specialised in the treatment of early psychosis, which tend to be developed in many countries. It is however important to match them to local needs as well as to the structure of local health services. This paper reviews elements that justify such a development in Lausanne, Switzerland, and describe its various elements.

Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.

OBJECTIVE: Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART. DESIGN: A randomized, observer-blind, controlled trial (NCT00707967). METHODS: HIV-infected adults on cART in Switzerland were randomized 3 : 1 : 1 to receive two doses, 1 month apart, of M72/AS01, AS01 or 0.9% physiological saline (N = 22, N = 8 and N = 7, respectively) and were followed up to 6 months postdose 2 (D210). Individuals with CD4⁺ cell counts below 200 cells/μl were excluded. Adverse events (AEs) including HIV-specific and laboratory safety parameters were recorded. Cell-mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1 month after each dose (D30, D60) and D210. RESULTS: Thirty-seven individuals [interquartile range (IQR) CD4⁺ cell counts at screening: 438-872 cells/μl; undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01 recipients, no vaccine-related serious AEs or cART-regimen adjustments were recorded, and there were no clinically relevant effects on laboratory safety parameters, HIV-1 viral loads or CD4⁺ cell counts. M72/AS01 was immunogenic, inducing persistent and polyfunctional M72-specific CD4⁺ T-cell responses [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210, predominantly CD40L⁺IL-2⁺TNF-α⁺, CD40L⁺IL-2⁺ and CD40L⁺IL-2⁺TNF-α⁺IFN-γ⁺]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second vaccination until study end. CONCLUSION: M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study

Introduction: We previously reported the results of a phase II study for patients with newly diagnosed primary CNS lymphoma (PCNSL) treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and responseadapted whole brain radiotherapy (WBRT). The purpose of this report is to update the initial results and provide long-term data regarding overall survival, prognostic factors, and the risk of treatment-related neurotoxicity.Methods: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been treated according to the ,,OSHO-53 study", which was initiated by the Ostdeutsche Studiengruppe Hamatologie-Onkologie. Between August 1999 and October 2004 twentythree patients with an average age of 55 and median Karnofsky performance score of 70% were enrolled and received high-dose mthotrexate (HD-MTX) on days 1 and 10. In case of at least a partial remission (PR), high-dose busulfan/ thiotepa (HD-BuTT) followed by aPBSCT was performed. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. All patients (n=8), who are alive in 2011, were contacted and Mini Mental State examination (MMSE) and the EORTC QLQ-C30 were performed.Results: Eight patients are still alive with a median follow-up of 116,9 months (79 - 141, range). One of them suffered from a late relapse eight and a half years after initial diagnosis of PCNSL, another one suffers from a gall bladder carcinoma. Both patients are alive, the one with the relapse of PCNSL has finished rescue therapy and is further observed, the one with gall baldder carcinoma is still under therapy. MMSE and QlQ-C30 showed impressive results in the patients, who were not irradiated. Only one of the irradiated patients is still alive with a clear neurologic deficit but acceptable quality of life.Conclusions: Long-term follow-up of our patients, who were included in the OSHO-53 study show an overall survival of 30 percent. If WBRT can be avoided no long-term neurotoxicity has been observed and the patients benefit from excellent Quality of Life. Induction chemotherapy with two cycles of HD-MTX should be intensified to improve the unsatisfactory OAS of 30 percent.

Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity.

Programme cantonal Diabète: bilan de la première phase du programme (2010-2011) et construction d'une théorie d'action.

Le Programme cantonal diabète (PCD) du canton de Vaud a pour objectifs de réduire durablement l'impact du diabète sur la population vaudoise. Il a été élaboré à l'initiative du Service de la santé publique du canton de Vaud et la stratégie du programme a été construite sur la base des propositions de plusieurs groupes de travail. Ce programme inclut divers projets complémentaires qui ont été progressivement mis sur pied à partir de 2010. 2012 marque la fin de la première phase du programme et une évaluation-bilan du programme est demandée. Cette évaluation-bilan fait suite à une première phase de travaux qui ont consisté en une évaluation de l'évaluabilité du programme. Les résultats de cette première phase ont été délivrés en décembre 2011 au groupe de pilotage et consignés dans un rapport en février 2012. L'IUMSP propose donc pour 2012 des travaux en continuité de ce qui a été fait en 2011 et qui vont dans le sens d'un bilan critique et de propositions pour un système de monitoring à long terme du programme, comportant des indicateurs d'activité (à harmoniser lorsque c'est possible dans des projets similaires), des indicateurs de couverture et de résultats. [p. 7]

Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C: a randomized phase II study.

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha-2a (Peg-IFN-α-2a) plus ribavirin (RBV). In this double-blind, placebo-controlled, dose-ranging study, treatment-naïve patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label Peg-IFN-α-2a (180 μg/week) and RBV (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg twice-daily [BID], 600 mg BID, 600 mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline in viral load, with HCV RNA levels approximately 3 log(10) IU/mL lower in vaniprevir-treated patients, compared to placebo recipients. Rates of RVR were significantly higher in each of the vaniprevir dose groups, compared to the control regimen (68.8%-83.3% versus 5.6%; P < 0.001 for all comparisons). There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir, as compared to placebo. Resistance profile was predictable, with variants at R155 and D168 detected in a small number of patients. No relationship between interleukin-28B genotype and treatment outcomes was demonstrated in this study. The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses. CONCLUSION: Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for QD or BID administration.