Oral Nitrate Supplementation Differentially Modulates Cerebral Artery Blood Velocity and Prefrontal Tissue Oxygenation During 15 km Time-Trial Cycling in Normoxia but Not in Hypoxia.

<b>Background:</b> Nitrate is a precursor of nitric oxide (NO), an important regulator of cerebral perfusion in normoxic and hypoxic conditions. Nitrate supplementation could be used to improve cerebral perfusion and oxygenation during exercise in hypoxia. The effects of dietary nitrate supplementation on cerebral haemodynamics during exercise in severe hypoxia (arterial O <sub>2</sub> saturation < 70%) have not been explored. <b>Methods:</b> In twelve trained male cyclists, we measured blood pressure (BP), middle cerebral artery blood velocity (MCAv), cerebrovascular resistance (CVR) and prefrontal oxyhaemoglobin and deoxyhaemoglobin concentration (O <sub>2</sub> Hb and HHb, respectively) during 15 km cycling time trials (TT) in normoxia and severe hypoxia (11% inspired O <sub>2</sub> , peripheral O <sub>2</sub> saturation ∼66%) following 3-day oral supplementation with placebo or sodium nitrate (0.1 mmol/kg/day) in a randomised, double-blinded manner. We tested the hypothesis that dietary nitrate supplementation increases MCAv and cerebral O <sub>2</sub> Hb during TT in severe hypoxia. <b>Results:</b> During TT in normoxia, nitrate supplementation lowered MCAv by ∼2.3 cm/s and increased cerebral O <sub>2</sub> Hb by ∼6.8 μM and HHb by ∼2.1 μM compared to normoxia placebo ( <i>p</i> ≤ 0.01 for all), while BP tended to be lowered ( <i>p</i> = 0.06). During TT in severe hypoxia, nitrate supplementation elevated MCAv (by ∼2.5 cm/s) and BP (by ∼5 mmHg) compared to hypoxia placebo ( <i>p</i> < 0.01 for both), while it had no effect on cerebral O <sub>2</sub> Hb ( <i>p</i> = 0.98), HHb ( <i>p</i> = 0.07) or PETCO <sub>2</sub> ( <i>p</i> = 0.12). Dietary nitrate had no effect of CVR during TT in normoxia or hypoxia ( <i>p</i> = 0.19). <b>Conclusion:</b> Our findings indicate that during normoxic TT, the modulatory effect of dietary nitrate on regional and global cerebral perfusion is heterogeneous. Meanwhile, the lack of major changes in cerebral perfusion with dietary nitrate during hypoxic TT alludes to an exhausted cerebrovascular reserve

Towards a computer aided diagnosis system dedicated to virtual microscopy based on stereology sampling and diffusion maps

An original strategy is presented, combining stereological sampling methods based on test grids and data reduction methods based on diffusion maps, in order to build a knowledge image database with no bias introduced by a subjective choice of exploration areas. The practical application of the exposed methodology concerns virtual slides of breast tumors

Global diabetes burden: analysis of regional differences to improve diabetes care.

peer reviewed[en] INTRODUCTION: The current evaluation processes of the burden of diabetes are incomplete and subject to bias. This study aimed to identify regional differences in the diabetes burden on a universal level from the perspective of people with diabetes. RESEARCH DESIGN AND METHODS: We developed a worldwide online diabetes observatory based on 34 million diabetes-related tweets from 172 countries covering 41 languages, spanning from 2017 to 2021. After translating all tweets to English, we used machine learning algorithms to remove institutional tweets and jokes, geolocate users, identify topics of interest and quantify associated sentiments and emotions across the seven World Bank regions. RESULTS: We identified four topics of interest for people with diabetes (PWD) in the Middle East and North Africa and another 18 topics in North America. Topics related to glycemic control and food are shared among six regions of the world. These topics were mainly associated with sadness (35% and 39% on average compared with levels of sadness in other topics). We also revealed several region-specific concerns (eg, insulin pricing in North America or the burden of daily diabetes management in Europe and Central Asia). CONCLUSIONS: The needs and concerns of PWD vary significantly worldwide, and the burden of diabetes is perceived differently. Our results will support better integration of these regional differences into diabetes programs to improve patient-centric diabetes research and care, focused on the most relevant concerns to enhance personalized medicine and self-management of PWD

Substructures in lens galaxies: PG1115+080 and B1555+375, two fold configurations

We study the anomalous flux ratio which is observed in some four-image lens systems, where the source lies close to a fold caustic. In this case two of the images are close to the critical curve and their flux ratio should be equal to unity, instead in several cases the observed value differs significantly. The most plausible solution is to invoke the presence of substructures, as for instance predicted by the Cold Dark Matter scenario, located near the two images. In particular, we analyze the two fold lens systems PG1115+080 and B1555+375, for which there are not yet satisfactory models which explain the observed anomalous flux ratios. We add to a smooth lens model, which reproduces well the positions of the images but not the anomalous fluxes, one or two substructures described as singular isothermal spheres. For PG1115+080 we consider a smooth model with the influence of the group of galaxies described by a SIS and a substructure with mass $\sim 10^{5} M_{\odot}$ as well as a smooth model with an external shear and one substructure with mass $\sim 10^{8} M_{\odot}$ . For B1555+375 either a strong external shear or two substructures with mass $\sim 10^{7} M_{\odot}$ reproduce the data quite well.Comment: 26 pages, updated bibliography, Accepted for publication in Astrophysics & Space Scienc

Photon mixing in universes with large extra-dimensions

In presence of a magnetic field, photons can mix with any particle having a two-photon vertex. In theories with large compact extra-dimensions, there exists a hierachy of massive Kaluza-Klein gravitons that couple to any photon entering a magnetic field. We study this mixing and show that, in comparison with the four dimensional situation where the photon couples only to the massless graviton, the oscillation effect may be enhanced due to the existence of a large number of Kaluza-Klein modes. We give the conditions for such an enhancement and then investigate the cosmological and astrophysical consequences of this phenomenon; we also discuss some laboratory experiments. Axions also couple to photons in the same way; we discuss the effect of the existence of bulk axions in universes with large extra-dimensions. The results can also be applied to neutrino physics with extra-dimensions.Comment: 41 pages, LaTex, 6 figure

Ornithological report 2001-2006 for the Camargue

The present ornithological report for the Camargue covers six years (2001-2006). This time-period has been marked by an accelerated global warming (the summer 2003 was particularly extreme). Owing to a constant high observation pressure, 18 new species have been recorded and many rare species have been resighted in that region (Camargue, Crau, Alpilles). Among the species or group of species which are regularly censused, the number of breeding Greater Flamingos Phoenicopterus roseus and that of wintering ducks and coots did not show any significant change. The colonial herons have continued either to increase or to fluctuate at a high level. For example, the Great White Egret Casmerodius albus has definitely settled in the delta and the Squacco Heron Ardeola ralloides has reached a new peak of 505 pairs in 2006. More efficient prospection efforts gave more precise breeding numbers for two species of solitary herons, the Great Bittern Botaurus stellaris and the Little Bittern Ixobrychus minutus. New breeding species such as the Great Cormorant Phalacrocorax carbo, White Stork Ciconia ciconia, Eurasian Spoonbill Platalea leucorodia and Greylag Anser anser increased their numbers as well as the Glossy Ibis Plegadis falcinellus of which 14 pairs has bred in 2006 and the Purple Swamphen Porphyrio porphyrio which was found for the first time breeding in 2006. The breeding species showing the most serious concern are actually the breeding gulls and terns whose figures have dramatically decreased. Without human management, this situation will even become worse in a near future. Further remarkable observations were the first case of wintering Lesser Spotted Eagle Aquila pomarina in 2001/2002, a mixed pair of Black-winged Pratincole Glareola nordmanni x Collared Pratincole G. pratincola in 2001, the settling of the Rook Corvus frugilegus in ArlesCe calendrier ornithologique couvre les six années de 2001 à 2006, une période marquée par un phénomène de réchauffement général accéléré du climat en général et par la canicule de l'été 2003 en particulier. Compte tenu de la pression d'observation élevée, 18 nouvelles espèces ont été signalées et de nombreuses espèces rares ont été revues dans la région (Camargue, Crau, Alpilles). Parmi les espèces ou groupes d'espèces qui font l'objet de recensements réguliers, les effectifs nicheurs de Flamant rose Phoenicopterus roseus de même que ceux des Anatidés et des Foulques hivernants n'appellent pas de commentaires particuliers pour ce laps de temps. Les Ardéidés coloniaux continuent soit de progresser pour certains, soit de fluctuer dans des limites qui restent élevées pour d'autres. Par exemple, la Grande Aigrette Casmerodius albus s'est installée durablement dans le delta, le Crabier chevelu Ardeola ralloides a atteint un nouveau maximum avec 505 couples en 2006. Des effectifs plus précis sont fournis pour deux espèces comme le Butoir étoilé Botaurus stellaris et le Blongios nain Ixohrychus minutus grâce à des prospections plus efficaces. Des espèces nicheuses d'installation récente comme le Grand Cormoran Phalacrocorax carho, la Cigogne blanche Ciconia ciconia, la Spatule blanche Platalea leucorodia et l'Oie cendrée Anser anser continuent de progresser de même que l'Ibis falcinelle Plegadis falcinellus dont 14 couples se sont reproduits en 2006 et la Talève sultane Porphyrio porphyrio dont la reproduction a enfin été confirmée en 2006. Parmi les espèces posant un problème grave, il faut relever les laro-limicoles nicheurs dont les effectifs se sont effondrés. Sans intervention urgente de gestion, leur situation risque d'empirer. Parmi les faits remarquables, signalons le premier cas d'hivernage de l'Aigle pomarin Aquila pomarina en 2001/2002, un couple mixte de Glaréole à ailes noires Glareola nordmanni x Glaréole à collier G. pratincola en 2001, l'installation du Corbeau freux Corvus frugilegus à Arles

The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain

ABSTRACT: BACKGROUND: The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC). However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC). METHODS: We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain. RESULTS: EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere. CONCLUSIONS: These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC.Peer reviewe

Detecting microsatellites within genomes: significant variation among algorithms

<p>Abstract</p> <p>Background</p> <p>Microsatellites are short, tandemly-repeated DNA sequences which are widely distributed among genomes. Their structure, role and evolution can be analyzed based on exhaustive extraction from sequenced genomes. Several dedicated algorithms have been developed for this purpose. Here, we compared the detection efficiency of five of them (TRF, Mreps, Sputnik, STAR, and RepeatMasker).</p> <p>Results</p> <p>Our analysis was first conducted on the human X chromosome, and microsatellite distributions were characterized by microsatellite number, length, and divergence from a pure motif. The algorithms work with user-defined parameters, and we demonstrate that the parameter values chosen can strongly influence microsatellite distributions. The five algorithms were then compared by fixing parameters settings, and the analysis was extended to three other genomes (<it>Saccharomyces cerevisiae</it>, <it>Neurospora crassa </it>and <it>Drosophila melanogaster</it>) spanning a wide range of size and structure. Significant differences for all characteristics of microsatellites were observed among algorithms, but not among genomes, for both perfect and imperfect microsatellites. Striking differences were detected for short microsatellites (below 20 bp), regardless of motif.</p> <p>Conclusion</p> <p>Since the algorithm used strongly influences empirical distributions, studies analyzing microsatellite evolution based on a comparison between empirical and theoretical size distributions should therefore be considered with caution. We also discuss why a typological definition of microsatellites limits our capacity to capture their genomic distributions.</p

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods. Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer dev

Spread of Avian Influenza Viruses by Common Teal (Anas crecca) in Europe

Since the recent spread of highly pathogenic (HP) H5N1 subtypes, avian influenza virus (AIV) dispersal has become an increasing focus of research. As for any other bird-borne pathogen, dispersal of these viruses is related to local and migratory movements of their hosts. In this study, we investigated potential AIV spread by Common Teal (Anas crecca) from the Camargue area, in the South of France, across Europe. Based on bird-ring recoveries, local duck population sizes and prevalence of infection with these viruses, we built an individual-based spatially explicit model describing bird movements, both locally (between wintering areas) and at the flyway scale. We investigated the effects of viral excretion duration and inactivation rate in water by simulating AIV spread with varying values for these two parameters. The results indicate that an efficient AIV dispersal in space is possible only for excretion durations longer than 7 days. Virus inactivation rate in the environment appears as a key parameter in the model because it allows local persistence of AIV over several months, the interval between two migratory periods. Virus persistence in water thus represents an important component of contamination risk as ducks migrate along their flyway. Based on the present modelling exercise, we also argue that HP H5N1 AIV is unlikely to be efficiently spread by Common Teal dispersal only