Combination of carbon isotope ratio with hydrogen isotope ratio determinations in sports drug testing.

Carbon isotope ratio (CIR) analysis has been routinely and successfully applied to doping control analysis for many years to uncover the misuse of endogenous steroids such as testosterone. Over the years, several challenges and limitations of this approach became apparent, e.g., the influence of inadequate chromatographic separation on CIR values or the emergence of steroid preparations comprising identical CIRs as endogenous steroids. While the latter has been addressed recently by the implementation of hydrogen isotope ratios (HIR), an improved sample preparation for CIR avoiding co-eluting compounds is presented herein together with newly established reference values of those endogenous steroids being relevant for doping controls. From the fraction of glucuronidated steroids 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-Hydroxy-5β-androstane-11,17-dione, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 3β-hydroxy-androst-5-en-17-one (DHEA), 5α- and 5β-androstane-3α,17β-diol (5aDIOL and 5bDIOL), 17β-hydroxy-androst-4-en-3-one and 17α-hydroxy-androst-4-en-3-one were included. In addition, sulfate conjugates of ANDRO, ETIO, DHEA, 3β-hydroxy-5α-androstan-17-one plus 17α- and androst-5-ene-3β,17β-diol were considered and analyzed after acidic solvolysis. The results obtained for the reference population encompassing n = 67 males and females confirmed earlier findings regarding factors influencing endogenous CIR. Variations in sample preparation influenced CIR measurements especially for 5aDIOL and 5bDIOL, the most valuable steroidal analytes for the detection of testosterone misuse. Earlier investigations on the HIR of the same reference population enabled the evaluation of combined measurements of CIR and HIR and its usefulness regarding both steroid metabolism studies and doping control analysis. The combination of both stable isotopes would allow for lower reference limits providing the same statistical power and certainty to distinguish between the endo- or exogenous origin of a urinary steroid.

Patterns of gravity induced aggregate migration during casting of fluid concretes

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration. (C) 2012 Elsevier Ltd. All rights reserved.

Origins, evolution, and phenotypic impact of new genes.

Ever since the pre-molecular era, the birth of new genes with novel functions has been considered to be a major contributor to adaptive evolutionary innovation. Here, I review the origin and evolution of new genes and their functions in eukaryotes, an area of research that has made rapid progress in the past decade thanks to the genomics revolution. Indeed, recent work has provided initial whole-genome views of the different types of new genes for a large number of different organisms. The array of mechanisms underlying the origin of new genes is compelling, extending way beyond the traditionally well-studied source of gene duplication. Thus, it was shown that novel genes also regularly arose from messenger RNAs of ancestral genes, protein-coding genes metamorphosed into new RNA genes, genomic parasites were co-opted as new genes, and that both protein and RNA genes were composed from scratch (i.e., from previously nonfunctional sequences). These mechanisms then also contributed to the formation of numerous novel chimeric gene structures. Detailed functional investigations uncovered different evolutionary pathways that led to the emergence of novel functions from these newly minted sequences and, with respect to animals, attributed a potentially important role to one specific tissue--the testis--in the process of gene birth. Remarkably, these studies also demonstrated that novel genes of the various types significantly impacted the evolution of cellular, physiological, morphological, behavioral, and reproductive phenotypic traits. Consequently, it is now firmly established that new genes have indeed been major contributors to the origin of adaptive evolutionary novelties.

Plate tectonics of the Altaids

Abstract: The Altaids consist in a huge accretionary-type belt extending from Siberia through Mon-golia, northern China, Kyrgyzstan and Kazakhstan. They were formed from the Vendian through the Jurassic by the accretion of numerous displaced and exotic terranes (e.g. island arc, ribbon microcontinent, seamount, basaltic plateau, back-arc basin). The number, nature and origin of the terranes differ according to the palaeotectonic models of the different authors. Thanks to a geo- dynamic study (i.e. definition of tectonic settings and elaboration of geodynamic scenarios) and plate tectonics modelling, this work aims to present an alternative model explaining the Palaeozoic palaeotectonic evolution of the Altaids. Based on a large set of compiled geological data related to palaeogeography and geodyna¬mic (e.g. sedimentology, stratigraphy, palaeobiogeography, palaeomagnetism, magmatism, me- tamorphism, tectonic...), a partly new classification of the terranes and sutures implicated in the formation of the Altaids is proposed. In the aim to elaborate plate tectonics reconstructions, it is necessary to fragment the present arrangement of continents into consistent geological units. To avoid confusion with existing terminology (e.g. tectonic units, tectono-stratigraphic units, micro- continents, terranes, blocks...), the new concept of "Geodynamic Units (GDU)" was introduced. A terrane may be formed by a set of GDUs. It consists of a continental and/or oceanic fragment which has its own kinematic and geodynamic evolution for a given period. With the same ap-proach, the life span and type of the disappeared oceans is inferred thanks to the study of the mate-rial contained in suture zones. The interpretation of the tectonic settings within the GDUs comple-ted by the restoration of oceans leads to the elaboration of geodynamic scenarios. Since the Wilson cycle was presented in 1967, numerous works demonstrated that the continental growth is more complex and results from diverse geodynamic scenarios. The identification of these scenarios and their exploitation enable to elaborate plate tectonics models. The models are self-constraining (i.e. space and time constraints) and contest or confirm in turn the geodynamic scenarios which were initially proposed. The Altaids can be divided into three domains: (1) the Peri-Siberian, (2) the Kazakhstan, and (3) the Tarim-North China domains. The Peri-Siberian Domain consists of displaced (i.e. Sayan Terrane Tuva-Mongolian, Lake-Khamsara Terrane) and exotic terranes (i.e. Altai-Mongolian and Khangai-Argunsky Terrane) accreted to Siberia from the Vendian through the Ordovician. Fol-lowing the accretion of these terranes, the newly formed Siberia active margin remained active un-til its part collision with the Kazakhstan Superterrane in the Carboniferous. The eastern part of the active margin (i.e. East Mongolia) continued to act until the Permian when the North-China Tarim Superterrane collided with it. The geodynamic evolution of the eastern part of the Peri-Siberian Domain (i.e. Eastern Mongolia and Siberia) is complicated by the opening of the Mongol-Okhotsk Ocean in the Silurian. The Kazakhstan Domain is composed of several continental terranes of East Gondwana origin amalgamated together during the Ordovician-Silurian time. After these different orogenic events, the Kazakhstan Superterrane evolved as a single superterrane until its collision with a Tarim-North China related-terrane (i.e. Tianshan-Hanshan Terrane) and Siberian Continent during the Devonian. This new organisation of the continents imply a continued active margin from Siberia, to North China through the Kazakhstan Superterrane and the closure of the Junggar- Balkash Ocean which implied the oroclinal bending of the Kazakhstan Superterrane during the entire Carboniferous. The formation history of the Tarim-North China Domain is less complex. The Cambrian northern passive margin became active in the Ordovician. In the Silurian, the South Tianshan back-arc Ocean was open and led to the formation of the Tianshan-Hanshan Terrane which collided with the Kazakhstan Superterrane during the Devonian. The collision between Siberia and the eastern part of the Tarim-North China continents (i.e. Inner Mongolia), implied by the closure of the Solonker Ocean, took place in the Permian. Since this time, the major part of the Altaids was formed, the Mongol-Okhotsk Ocean only was still open and closed during the Jurassic. Résumé: La chaîne des Altaïdes est une importante chaîne d'accrétion qui s'étend en Sibérie, Mon-golie, Chine du Nord, Kirghizstan et Kazakhstan. Elle s'est formée durant la période du Vendian au Jurassique par l'accrétion de nombreux terranes déplacés ou exotiques (par exemple arc océa-nique, microcontinent, guyot, plateau basaltique, basin d'arrière-arc...). Le nombre, la nature ou encore l'origine diffèrent selon les modèles paléo-tectoniques proposés par les différents auteurs. Grâce à une étude géodynamique (c'est-à-dire définition des environnements tectoniques et éla-boration de scénarios géodynamiques) et à la modélisation de la tectonique des plaques, ce travail propose un modèle alternatif expliquant l'évolution paléo-tectonique des Altaïdes. Basé sur une large compilation de données géologiques pertinentes en termes de paléo-géographie et de géodynamique (par exemple sédimentologie, stratigraphie, paléo-biogéographie, paléomagnétisme, magmatisme, métamorphisme, tectonique...), une nouvelle classification des terranes et des sutures impliqués dans la formation des Altaïdes est proposée. Dans le but d'élabo¬rer des reconstructions de plaques tectoniques, il est nécessaire de fragmenter l'arrangement actuel des continents en unités tectoniques cohérentes. Afin d'éviter les confusions avec la terminolo¬gie existante (par exemple unité tectonique, unité tectono-stratigraphique, microcontinent, block, terrane...), le nouveau concept d' "Unité Géodynamique (UGD)" a été introduit. Un terrane est formé d'une ou plusieurs UGD et représente un fragment océanique ou continental défini pas sa propre cinétique et évolution géodynamique pour une période donnée. Parallèlement, la durée de vie et le type des océans disparus (c'est-à-dire principal ou secondaire) est déduite grâce à l'étude du matériel contenu dans les zones de sutures. L'interprétation des environnements tectoniques des UGD associés à la restauration des océans mène à l'élaboration de scénarios géodynamiques. Depuis que le Cycle de Wilson a été présenté en 1967, de nombreux travaux ont démontré que la croissance continentale peut résulter de divers scénarios géodynamiques. L'identification et l'ex-ploitation de ces scénarios permet finalement l'élaboration de modèles de tectonique des plaques. Les modèles sont auto-contraignants (c'est-à-dire contraintes spatiales et temporelles) et peuvent soit contester ou confirmer les scénarios géodynamiques initialement proposés. Les Altaïdes peuvent être divisées en trois domaines : (1) le Domaine Péri-Sibérien, (2) le Domaine Kazakh, et (3) le Domaine Tarim-Nord Chinois. Le Domaine Péri-Sibérien est composé de terranes déplacés (c'est-à-dire Terrane du Sayan, Tuva-Mongol et Lake-Khamsara) et exotiques (c'est-à-dire Terrane Altai-Mongol et Khangai-Argunsky) qui ont été accrétés au craton Sibérien durant la période du Vendien à l'Ordovicien. Suite à l'accrétion de ces terranes, la marge sud-est de la Sibérie nouvellement formée reste active jusqu'à sa collision partielle avec le Superterrane Ka-zakh au Carbonifère. La partie est de la marge active (c'est-à-dire Mongolie de l'est) continue son activité jusqu'au Permien lors de sa collision avec le Superterrane Tarim-Nord Chinois. L'évolu¬tion géodynamique de la partie est du Domaine Sibérien est compliquée par l'ouverture Silurienne de l'Océan Mongol-Okhotsk qui disparaîtra seulement au Jurassique. Le Domaine Kazakh est composé de plusieurs terranes d'origine est-Gondwanienne accrétés les uns avec les autres avant ou pendant le Silurien inférieur et leurs evolution successive sous la forme d'un seul superterrane. Le Superterrane Kazakh collisione avec un terrane Tarim-Nord Chinois (c'est-à-dire Terrane du Tianshan-Hanshan) durant le Dévonien et le continent Sibérien au Dévonien supérieur. Ce nouvel agencement des plaques induit une marge active continue le long des continents Sibérien, Kazakh et Nord Chinois et la fermeture de l'Océan Junggar-Balkash qui provoque le plissement oroclinal du Superterrane Kazakh durant le Carbonifère. L'histoire de la formation du Domaine Tarim-Nord Chinois est moins complexe. La marge passive nord Cambrienne devient active à l'Ordovicien et l'ouverture Silurienne du bassin d'arrière-arc du Tianshan sud mène à la formation du terrane du Tianshan-Hanshan. La collision Dévonienne entre ce dernier et le Superterrane Kazakh provoque la fermerture de l'Océan Tianshan sud. Finalement, la collision entre la Sibérie et la partie est du continent Tarim-Nord Chinois (c'est-à-dire Mongolie Intérieure) prend place durant le Permien suite à la fermeture de l'Océan Solonker. La majeure partie des Altaïdes est alors formée, seul l'Océan Mongol-Okhotsk est encore ouvert. Ce dernier se fermera seulement au Jurassique.

Anthropogenic disturbance as a driver of microspatial and microhabitat segregation of cytotypes of Centaurea stoebe and cytotype interactions in secondary contact zones.

BACKGROUND AND AIMS: In a mixed-ploidy population, strong frequency-dependent mating will lead to the elimination of the less common cytotype, unless prezygotic barriers enhance assortative mating. However, such barriers favouring cytotype coexistence have only rarely been explored. Here, an assessment is made of the mechanisms involved in formation of mixed-ploidy populations and coexistence of diploid plants and their closely related allotetraploid derivates from the Centaurea stoebe complex (Asteraceae). METHODS: An investigation was made of microspatial and microhabitat distribution, life-history and fitness traits, flowering phenology, genetic relatedness of cytotypes and intercytotype gene flow (cpDNA and microsatellites) in six mixed-ploidy populations in Central Europe. KEY RESULTS: Diploids and tetraploids were genetically differentiated, thus corroborating the secondary origin of contact zones. The cytotypes were spatially segregated at all sites studied, with tetraploids colonizing preferentially drier and open microhabitats created by human-induced disturbances. Conversely, they were rare in more natural microsites and microsites with denser vegetation despite their superior persistence ability (polycarpic life cycle). The seed set of tetraploid plants was strongly influenced by their frequency in mixed-ploidy populations. Triploid hybrids originated from bidirectional hybridizations were extremely rare and almost completely sterile, indicating a strong postzygotic barrier between cytotypes. CONCLUSIONS: The findings suggest that tetraploids are later immigrants into already established diploid populations and that anthropogenic activities creating open niches favouring propagule introductions were the major factor shaping the non-random distribution and habitat segregation of cytotypes at fine spatial scale. Establishment and spread of tetraploids was further facilitated by their superior persistence through the perennial life cycle. The results highlight the importance of non-adaptive spatio-temporal processes in explaining microhabitat and microspatial segregation of cytotypes.

The influence of social structure on brood survival and development in a socially polymorphic ant: insights from a cross-fostering experiment.

Animal societies vary in the number of breeders per group, which affects many socially and ecologically relevant traits. In several social insect species, including our study species Formica selysi, the presence of either one or multiple reproducing females per colony is generally associated with differences in a suite of traits such as the body size of individuals. However, the proximate mechanisms and ontogenetic processes generating such differences between social structures are poorly known. Here, we cross-fostered eggs originating from single-queen (= monogynous) or multiple-queen (= polygynous) colonies into experimental groups of workers from each social structure to investigate whether differences in offspring survival, development time and body size are shaped by the genotype and/or prefoster maternal effects present in the eggs, or by the social origin of the rearing workers. Eggs produced by polygynous queens were more likely to survive to adulthood than eggs from monogynous queens, regardless of the social origin of the rearing workers. However, brood from monogynous queens grew faster than brood from polygynous queens. The social origin of the rearing workers influenced the probability of brood survival, with workers from monogynous colonies rearing more brood to adulthood than workers from polygynous colonies. The social origin of eggs or rearing workers had no significant effect on the head size of the resulting workers in our standardized laboratory conditions. Overall, the social backgrounds of the parents and of the rearing workers appear to shape distinct survival and developmental traits of ant brood.

Swine monoclonal antibodies of high affinity and specificity to carcinoembryonic antigen.

To avoid the exclusive use of rodent monoclonal antibodies (MAbs) in patients for the detection of tumors by immunoscintigraphy and for radioimmunotherapy, swine MAbs were produced that are directed against carcinoembryonic antigen (CEA). Spleen cells from 2 pigs immunized with purified colon carcinoma CEA were fused with a nonsecreting mouse myeloma cell line by conventional methods, except that a particularly long immunization protocol and large amounts of spleen and myeloma cells were used. Of 1,200 growing hybrids tested, 20 were found initially to produce antibodies binding to radiolabeled CEA. Seven stable clones producing anti-CEA MAbs for more than 6 months were derived from these hybrids by repeated subcloning. The pig origin of the seven MAbs was demonstrated in a solid-phase CEA enzyme immunoassay where anti-pig immunoglobin (Ig) antibodies coupled to peroxidase gave a positive reaction while anti-mouse Ig antibodies were entirely negative. All swine MAbs were of the IgG isotype. Three anti-CEA MAbs showed no cross-reactivity with granulocytes, while four others gave various degrees of reactivity with different granulocyte glycoproteins. Competitive binding to CEA performed for two purified swine MAbs showed that they recognized two different epitopes. The affinity constants measured for these two MAbs by Scatchard plot on purified CEA were high (1.2 X 10(9) and 1.2 X 10(10) liter/mol). One of the MAbs was tested in vivo for tumor localization by injection, after radiolabeling, in nude mice bearing human colon carcinoma xenograft. High ratios of tumor to normal tissue were obtained with mean values of 10.5 for intact MAbs and of 26.8 for F(ab')2 fragments of the porcine MAb. The results showed that heterofusion with this particular protocol can be used to produce swine MAbs of high affinity and specificity for a well-defined tumor marker. These reagents may have an important clinical utility, particularly in patients who became sensitized to mouse immunoglobulins.

Integrative analyses of speciation and divergence in Psammodromus hispanicus (Squamata: Lacertidae).

BackgroundGenetic, phenotypic and ecological divergence within a lineage is the result of past and ongoing evolutionary processes, which lead ultimately to diversification and speciation. Integrative analyses allow linking diversification to geological, climatic, and ecological events, and thus disentangling the relative importance of different evolutionary drivers in generating and maintaining current species richness.ResultsHere, we use phylogenetic, phenotypic, geographic, and environmental data to investigate diversification in the Spanish sand racer (Psammodromus hispanicus). Phylogenetic, molecular clock dating, and phenotypic analyses show that P. hispanicus consists of three lineages. One lineage from Western Spain diverged 8.3 (2.9-14.7) Mya from the ancestor of Psammodromus hispanicus edwardsianus and P. hispanicus hispanicus Central lineage. The latter diverged 4.8 (1.5-8.7) Mya. Molecular clock dating, together with population genetic analyses, indicate that the three lineages experienced northward range expansions from southern Iberian refugia during Pleistocene glacial periods. Ecological niche modelling shows that suitable habitat of the Western lineage and P. h. edwardsianus overlap over vast areas, but that a barrier may hinder dispersal and genetic mixing of populations of both lineages. P. h. hispanicus Central lineage inhabits an ecological niche that overlaps marginally with the other two lineages.ConclusionsOur results provide evidence for divergence in allopatry and niche conservatism between the Western lineage and the ancestor of P. h. edwardsianus and P. h. hispanicus Central lineage, whereas they suggest that niche divergence is involved in the origin of the latter two lineages. Both processes were temporally separated and may be responsible for the here documented genetic and phenotypic diversity of P. hispanicus. The temporal pattern is in line with those proposed for other animal lineages. It suggests that geographic isolation and vicariance played an important role in the early diversification of the group, and that lineage diversification was further amplified through ecological divergence.

Diagnostic et prise en charge des douleurs de la région scapulaire [Diagnosis and treatments of scapular pain].

Shoulder pain is one of the most common reasons for bone and joint consultations in general practice. In most situations, it is due to a lesion of the rotator cuff. A detailed history can often exclude a cervical or visceral origin of the pain. A full clinical examination especially active and passive mobility provides a good diagnostic approach. It can be refined by specific clinical tests that must nevertheless be interpreted with caution. The management of pathologies of the rotator cuff does not require imaging immediately. Ultrasound is increasingly recognized as the imaging procedure of choice in most situations. For abarticular shoulder pathologies, therapy is primarily conservative. The exact role of infiltration of steroids remains unclear. Only an acute traumatic rupture of the rotator cuff warrants prompt surgical intervention.

The carbon isotope composition of natural SiC (moissanite) from the Earth's mantle: New discoveries from ophiolites

Moissanite (natural SiC) has been recovered from podiform chromitites of several ophiolite complexes, including the Luobusa and Donqiao ophiolites in Tibet, the Semail ophiolite in Oman and the United Arab Emirates, and the Ray-Iz ophiolite of the Polar Urals, Russia. Taking these new occurrences with the numerous earlier reports of moissanite in diamondiferous kimberlites leads to the conclusion that natural SiC is a widespread mineral in the Earth's mantle, which implies at least locally extremely low redox conditions. The ophiolite moissanite grains are mostly fragments (20 to 150 mu m) with one or more crystal faces, but some euhedral hexagonal grains have also been recovered. Twinned crystals are common in chromitites from the Luobusa ophiolite. The moissanite is rarely colorless, more commonly light bluish-gray to blue or green. Many grains contain inclusions of native Si and Fe-Si alloys (FeSi(2), Fe(3)Si(7)). Secondary ion mass spectrometric (SIMS) analysis shows that the ophiolite-hosted moissanite has a distinctive (13)C-depleted isotopic composition (delta(13)C from -18 to -35 parts per thousand, n=36), much lighter than the main carbon reservoir in the upper mantle (delta(13)C near -5 parts per thousand). The compiled data from moissanite from kimberlites and other mantle settings share the characteristic of strongly (13)C-depleted isotopic composition. This suggests that moissanite originates from a separate carbon reservoir in the mantle or that its formation involved strong isotopic fractionation. The degree of fractionation needed to produce the observed moissanite compositions from the main C-reservoir would be unrealistically large at the high temperatures required for moissanite formation. Subduction of biogenic carbonaceous material could potentially satisfy both the unusual isotopic and redox constraints on moissanite formation, but this material would need to stay chemically isolated from the upper mantle until it reached the high-T stability field of moissanite. The origin of moissanite in the mantle is still unsolved, but all evidence from the upper mantle indicates that it cannot have formed there, barring special and local redox conditions. We suggest, alternatively, that moissanite may have formed in the lower mantle, where the existence of (13)C-depleted carbon is strongly supported by studies of extraterrestrial carbon (Mars, Moon, meteorites). (C) 2009 Elsevier B. V. All rights reserved.

Relaxed selection is a precursor to the evolution of phenotypic plasticity.

Phenotypic plasticity allows organisms to produce alternative phenotypes under different conditions and represents one of the most important ways by which organisms adaptively respond to the environment. However, the relationship between phenotypic plasticity and molecular evolution remains poorly understood. We addressed this issue by investigating the evolution of genes associated with phenotypically plastic castes, sexes, and developmental stages of the fire ant Solenopsis invicta. We first determined if genes associated with phenotypic plasticity in S. invicta evolved at a rapid rate, as predicted under theoretical models. We found that genes differentially expressed between S. invicta castes, sexes, and developmental stages all exhibited elevated rates of evolution compared with ubiquitously expressed genes. We next investigated the evolutionary history of genes associated with the production of castes. Surprisingly, we found that orthologs of caste-biased genes in S. invicta and the social bee Apis mellifera evolved rapidly in lineages without castes. Thus, in contrast to some theoretical predictions, our results suggest that rapid rates of molecular evolution may not arise primarily as a consequence of phenotypic plasticity. Instead, genes evolving under relaxed purifying selection may more readily adopt new forms of biased expression during the evolution of alternate phenotypes. These results suggest that relaxed selective constraint on protein-coding genes is an important and underappreciated element in the evolutionary origin of phenotypic plasticity.

Stable carbon isotope Composition of c9,t11-conjugated linoleic acid in cow's milk as related to dietary fatty acids

This study explores the potential use of stable carbon isotope ratios (delta C-13) of single fatty acids (FA) as tracers for the transformation of FA from diet to milk, with focus on the metabolic origin of c9,t11-18:2. For this purpose, dairy cows were fed diets based exclusively on C-3 and C-4 plants. The FA in milk and feed were fractionated by silver-ion thin-layer chromatography and analyzed for their delta C-13 values. Mean delta C-13 values of FA from C-3 milk were lower compared to those from C-4 milk (-30.1aEuro degrees vs. -24.9aEuro degrees, respectively). In both groups the most negative delta C-13 values of all FA analyzed were measured for c9,t11-18:2 (C-3 milk = -37.0 +/- A 2.7aEuro degrees; C-4 milk -31.4 +/- A 1.4aEuro degrees). Compared to the dietary precursors 18:2n-6 and 18:3n-3, no significant C-13-depletion was measured in t11-18:1. This suggests that the delta C-13-change in c9,t11-18:2 did not originate from the microbial biohydrogenation in the rumen, but most probably from endogenous desaturation of t11-18:1. It appears that the natural delta C-13 differences in some dietary FA are at least partly preserved in milk FA. Therefore, carbon isotope analyses of individual FA could be useful for studying metabolic transformation processes in ruminants.

Stable O and H isotopic composition of hydrous minerals as proxies for paleoclimate and -topography : application to the European Alps

The isotopie composition of clay minerals can be used to gain information on paleoaltitude, -topography and -climate during the time of their formation, as they form in isotopie equilibrium with ambient water, which has an isotopie composition that is determined by previous rain-out. In this thesis, the usability of this approach is evaluated for sample material from both the North Alpine Foreland Basin and internal parts of the European Alps. The isotopie composition of precipitation is determined by the air temperature and the extent of previous rain-out, which in turn is affected by the distance to the point of origin of the water vapor and the condensation conditions. An orographic barrier leads to uplift and adiabatic cooling of air masses and thereby enhances rainfall with a characteristic depletion in heavy 0 and H isotopes. Processes such as evaporation and mixing of water with different origin affect the isotopie composition further on the surface. Clay minerals are hydrous phyllosilicates that can form during weathering or pedogenesis in isotopie equilibrium with the present water and inherit its isotopie composition with a characteristic fractionation. If their isotopie composition was preserved after formation and the necessary parameters are known, it is possible to calculate the isotopie composition of the ambient water and thereby reconstruct climatic and topographic conditions during their formation. Due to the hygroscopic behavior of the sample material, analytical procedures needed to be modified to allow an analysis of the oxygen and hydrogen isotopie composition of the hydroxyl water built into their crystal structure and not the one of recently adsorbed water. In order to determine typical 5lsO and 8D values of meteoric water and minerals in the weathering environment in high Alpine regions, samples of surface water and soils from the valley of Visp in the Swiss Alps were studied that were collected along a transect with varying altitudes and host rock lithologies. The actual aim to attempt the reconstruction of Alpine paleoelevations was addressed by the analysis of sediments deposited under marine and terrestrial conditions during the Miocene and Oligocene, which were sampled from different locations in Switzerland, Germany and Austria. Further bentonite and fault gouge clay samples were used as reference material from low and high elevations. Results show that the isotopie composition of clay minerals can be influenced by several factors, such as the mode and site of their formation, possible isotope exchange (which is evident for 8D values), the samples' mineral composition (such as the presence of detrital material) and the deposition environment. With a consideration of these parameters and limitation to certain sample material, conclusions are drawn on the isotopie composition of the water from which the clay minerals formed. Most of the obtained values lie in the same range as has been reported in literature for foreland precipitation. The reconstruction of paleoelevation might be possible for selected sites with a geographical setting close to the Alpine chain or for intramontane basins. - La composition isotopique des argiles, qui se forment typiquement en contact avec des eaux superficielles, peut être utilisée pour obtenir des informations sur la paléoaltitude, la paléotopographie et le paléoclimat pendant leur création. La composition en isotopes stable (oxygène et hydrogène) des eaux de pluie est déterminée par l'altitude, la température, la distance depuis le lieu d'évaporation et par le taux de précipitation. Certains processus comme l'évaporation, l'interaction avec des minéraux et le mélange d'eaux d'origines variées peuvent aussi changer la composition des eaux de surface. Les argiles sont des pliyllosilicates hydratés qui sont crées par l'altération des roches au contact de ces eaux de surface et ils acquièrent une composition isotopique qui est soumise à un certain fractionnement. L'objectif de cette thèse est d'évaluer si l'effet de l'altitude des Alpes, est détectable dans la composition isotopique des sédiments du bassin d'avant-pavs pendant le Miocène. Après avoir établi la procédure analytique, des compositions isotopiques typiques de régions de hautes altitudes ont été determine sur les eaux de surfaces (rivières) et sur des échantillons de sols, le long d'une coupe dans la valée de Visp, dans les Alpes Suisses. Une reconstruction des paléoaltitudes Miocènes Alpines a ensuite été mené par l'analyse de sédiments marins et terrestres en utilisant des échantillons d'âges variés et provenant de Suisse, d'Allemagne et d'Autriche. Les résultats montrent que la composition isotopique des échantillons est impactée par de multiples facteurs, tels que le mode de et le lieu de formation. un possible échange isotopique tardif (surtout pour 5D). leur composition minéralogique et l'environnement de leur sédimentation. Après un examen prudent de ces paramètres, et en se limitant à un certain assortiment d'échatillons, on peut tirer des conclusions sur la composition isotopique des eaux originelles pour en déduire l'effet du climat et de la topographie.

18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.

Residual antimalarial concentrations before treatment in patients with malaria from Cambodia: indication of drug pressure.

BACKGROUND: The Thai-Cambodian border has been known as the origin of antimalarial drug resistance for the past 30 years. There is a highly diverse market for antimalarials in this area, and improved knowledge of drug pressure would be useful to target interventions aimed at reducing inappropriate drug use. METHODS: Baseline samples from 125 patients with falciparum malaria recruited for 2 in vivo studies (in Preah Vihear and Pursat provinces) were analyzed for the presence of 14 antimalarials in a single run, by means of a liquid chromatography-tandem mass spectrometry assay. RESULTS: Half of the patients had residual drug concentrations above the lower limit of calibration for at least 1 antimalarial at admission. Among the drugs detected were the currently used first-line drugs mefloquine (25% and 35% of patients) and piperaquine (15% of patients); the first-line drug against vivax malaria, chloroquine (25% and 41% of patients); and the former first-line drug, quinine (5% and 34% patients). CONCLUSIONS: The findings demonstrate that there is high drug pressure and that many people still seek treatment in the private and informal sector, where appropriate treatment is not guaranteed. Promotion of comprehensive behavioral change, communication, community-based mobilization, and advocacy are vital to contain the emergence and spread of parasite resistance against new antimalarials.