Showing papers by "University of Nice Sophia Antipolis published in 2014"

Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria

Abstract: In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)

Abstract: OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

Consensus guidelines for the detection of immunogenic cell death

Abstract: Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Prevalence of malnutrition and current use of nutrition support in patients with cancer.

Abstract: Background and Aims: The aim of this study was to evaluate on 1 day the prevalence of malnutrition in different types of cancer and the use of nutrition support in patients with cancer. Methods: A 1-day prevalence survey was carried out in 154 French hospital wards. Malnutrition was defined as a body mass index (BMI) 10% since disease onset. Oral food intake was measured using a visual analog scale. Results: Nutrition status was collected for 1903 patients (1109 men and 794 women, 59.3 ± 13.2 years). Cancer was local in 25%, regional in 31%, and metastatic in 44% of patients. Performance status was 0 or 1 in 49.8%, 2 in 23.7%, 3 or 4 in 19.6% and not available in 6.5% of patients. Overall, 39% of patients were malnourished. The prevalence of malnutrition by disease site was as follows: head and neck, 48.9%; leukemia/lymphoma, 34.0%; lung, 45.3%; colon/rectum, 39.3%; esophagus and/or stomach, 60.2%; pancreas, 66.7%; b...

Metric measure spaces with Riemannian Ricci curvature bounded from below

Abstract: In this paper, we introduce a synthetic notion of Riemannian Ricci bounds from below for metric measure spaces (X,d,m) which is stable under measured Gromov– Hausdorff convergence and rules out Finsler geometries. It can be given in terms of an enforcement of the Lott, Sturm, and Villani geodesic convexity condition for the entropy coupled with the linearity of the heat flow. Besides stability, it enjoys the same tensorization, global-to-local, and local-to-global properties. In these spaces, which we call RCD(K,∞) spaces, we prove that the heat flow (which can be equivalently characterized either as the flow associated to the Dirichlet form, or as the Wasserstein gradient flow of the entropy) satisfies Wasserstein contraction estimates and several regularity properties, in particular Bakry–Emery estimates and the L∞-Lip Feller regularization. We also prove that the distance induced by the Dirichlet form coincides with d, that the local energy measure has density given by the square of Cheeger’s relaxed slope, and, as a consequence, that the underlying Brownian motion has continuous paths. All these results are obtained independently of Poincare and doubling assumptions on the metric measure structure and therefore apply also to spaces which are not locally compact, as the infinite-dimensional ones.

Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source

Abstract: Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes.

EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Abstract: Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.

A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement

Abstract: Mitochondrial DNA instability disorders are responsible for a large clinical spectrum, among which amyotrophic lateral sclerosis-like symptoms and frontotemporal dementia are extremely rare. We report a large family with a late-onset phenotype including motor neuron disease, cognitive decline resembling frontotemporal dementia, cerebellar ataxia and myopathy. In all patients, muscle biopsy showed ragged-red and cytochrome c oxidase-negative fibres with combined respiratory chain deficiency and abnormal assembly of complex V. The multiple mitochondrial DNA deletions found in skeletal muscle revealed a mitochondrial DNA instability disorder. Patient fibroblasts present with respiratory chain deficiency, mitochondrial ultrastructural alterations and fragmentation of the mitochondrial network. Interestingly, expression of matrix-targeted photoactivatable GFP showed that mitochondrial fusion was not inhibited in patient fibroblasts. Using whole-exome sequencing we identified a missense mutation (c.176C>T; p.Ser59Leu) in the CHCHD10 gene that encodes a coiled-coil helix coiled-coil helix protein, whose function is unknown. We show that CHCHD10 is a mitochondrial protein located in the intermembrane space and enriched at cristae junctions. Overexpression of a CHCHD10 mutant allele in HeLa cells led to fragmentation of the mitochondrial network and ultrastructural major abnormalities including loss, disorganization and dilatation of cristae. The observation of a frontotemporal dementia-amyotrophic lateral sclerosis phenotype in a mitochondrial disease led us to analyse CHCHD10 in a cohort of 21 families with pathologically proven frontotemporal dementia-amyotrophic lateral sclerosis. We identified the same missense p.Ser59Leu mutation in one of these families. This work opens a novel field to explore the pathogenesis of the frontotemporal dementia-amyotrophic lateral sclerosis clinical spectrum by showing that mitochondrial disease may be at the origin of some of these phenotypes.

"Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease.

Abstract: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis. We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis. The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers. COPD patients were monitored annually by low-dose spiral CT. CTCs were detected in 3% of COPD patients (5 out of 168 patients). The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer. Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence. CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype. No CTCs were detected in control smoking and non-smoking healthy individuals. CTCs can be detected in patients with COPD without clinically detectable lung cancer. Monitoring “sentinel” CTC-positive COPD patients may allow early diagnosis of lung cancer.

Calculus and heat flow in metric measure spaces and applications to spaces with Ricci bounds from below

Abstract: This paper is devoted to a deeper understanding of the heat flow and to the refinement of calculus tools on metric measure spaces $(X,\mathsf {d},\mathfrak {m})$ . Our main results are: Our results apply in particular to spaces satisfying Ricci curvature bounds in the sense of Lott and Villani (Ann. Math. 169:903–991, 2009) and Sturm (Acta Math. 196: 65–131, 2006, and Acta Math. 196:133–177, 2006) and require neither the doubling property nor the validity of the local Poincare inequality.

The VIMOS Public Extragalactic Redshift Survey (VIPERS) - an unprecedented view of galaxies and large-scale structure at 0.5 < z < 1.2

Abstract: We describe the construction and general features of VIPERS, the VIMOS Public Extragalactic Redshift Survey. This `Large Programme' has been using the ESO VLT with the aim of building a spectroscopic sample of ~100,000 galaxies with i_{AB}<22.5 and 0.5

Autophagy in osteoblasts is involved in mineralization and bone homeostasis.

Abstract: Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies.

Metabolic response to the stress of critical illness

Abstract: The metabolic response to stress is part of the adaptive response to survive critical illness. Several mechanisms are well preserved during evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors, triggered to increase the provision of energy substrates to the vital tissues. The pathways of energy production are altered and alternative substrates are used as a result of the loss of control of energy substrate utilization by their availability. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycaemia, changes in body composition, and psychological and behavioural problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake, and early mobilization, are investigated. This review aims to summarize the pathophysiological mechanisms, the clinical consequences, and therapeutic implications of the metabolic response to stress.

Planetary population synthesis coupled with atmospheric escape: a statistical view of evaporation

Abstract: We apply hydrodynamic evaporation models to different synthetic planet populations that were obtained from a planet formation code based on the core-accretion paradigm. We investigated the evolution of the planet populations using several evaporation models, which are distinguished by the driving force of the escape flow (X-ray or EUV), the heating efficiency in energy-limited evaporation regimes, or both. Although the mass distribution of the planet populations is barely affected by evaporation, the radius distribution clearly shows a break at approximately 2R(circle plus). We find that evaporation can lead to a bimodal distribution of planetary sizes and to an "evaporation valley" running diagonally downward in the orbital distance-planetary radius plane, separating bare cores from low-mass planets that have kept some primordial H/He. Furthermore, this bimodal distribution is related to the initial characteristics of the planetary populations because low-mass planetary cores can only accrete small primordial H/He envelopes and their envelope masses are proportional to their core masses. We also find that the population-wide effect of evaporation is not sensitive to the heating efficiency of energy-limited description. However, in two extreme cases, namely without evaporation or with a 100% heating efficiency in an evaporation model, the final size distributions show significant differences; these two scenarios can be ruled out from the size distribution of Kepler candidates.

Polyunsaturated phospholipids facilitate membrane deformation and fission by endocytic proteins

Abstract: Phospholipids (PLs) with polyunsaturated acyl chains are extremely abundant in a few specialized cellular organelles such as synaptic vesicles and photoreceptor discs, but their effect on membrane properties is poorly understood. Here, we found that polyunsaturated PLs increased the ability of dynamin and endophilin to deform and vesiculate synthetic membranes. When cells incorporated polyunsaturated fatty acids into PLs, the plasma membrane became more amenable to deformation by a pulling force and the rate of endocytosis was accelerated, in particular, under conditions in which cholesterol was limiting. Molecular dynamics simulations and biochemical measurements indicated that polyunsaturated PLs adapted their conformation to membrane curvature. Thus, by reducing the energetic cost of membrane bending and fission, polyunsaturated PLs may help to support rapid endocytosis.

A High-Definition View of Functional Genetic Variation from Natural Yeast Genomes

Abstract: The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies.

The absolute magnitude distribution of kuiper belt objects

Abstract: Here we measure the absolute magnitude distributions (H-distribution) of the dynamically excited and quiescent (hot and cold) Kuiper Belt objects (KBOs), and test if they share the same H-distribution as the Jupiter Trojans. From a compilation of all useable ecliptic surveys, we find that the KBO H-distributions are well described by broken power laws. The cold population has a bright-end slope, ɑ_1 = 1.5_(-0.2)^(+0.4), and break magnitude, H_B = 6.9_(-0.2)^(+0.1)(r'-band). The hot population has a shallower bright-end slope of, ɑ_1 = 0.87_(-0.2)^(+0.07), and break magnitude H_g B = 7.7_(-0.5)^(+1.0). Both populations share similar faint-end slopes of α_2 ~ 0.2. We estimate the masses of the hot and cold populations are ~0.01 and ~3 × 10^(–4) M_⊕. The broken power-law fit to the Trojan H-distribution has α_1 = 1.0 ± 0.2, α_2 = 0.36 ± 0.01, and H_B = 8.3. The Kolmogorov-Smirnov test reveals that the probability that the Trojans and cold KBOs share the same parent H-distribution is less than 1 in 1000. When the bimodal albedo distribution of the hot objects is accounted for, there is no evidence that the H-distributions of the Trojans and hot KBOs differ. Our findings are in agreement with the predictions of the Nice model in terms of both mass and H-distribution of the hot and Trojan populations. Wide-field survey data suggest that the brightest few hot objects, with H_r' ≾ 3, do not fall on the steep power-law slope of fainter hot objects. Under the standard hierarchical model of planetesimal formation, it is difficult to account for the similar break diameters of the hot and cold populations given the low mass of the cold belt.

The APOGEE Red-clump Catalog: Precise Distances, Velocities, and High-resolution Elemental Abundances over a Large Area of the Milky Way's Disk

Abstract: The Sloan Digital Sky Survey III's Apache Point Observatory Galactic Evolution Experiment (APOGEE) is a high-resolution near-infrared spectroscopic survey covering all of the major components of the Galaxy, including the dust-obscured regions of the inner Milky Way disk and bulge. Here we present a sample of 10,341 likely red-clump stars (RC) from the first two years of APOGEE operations, selected based on their position in color-metallicity-surface-gravity-effective-temperature space using a new method calibrated using stellar evolution models and high-quality asteroseismology data. The narrowness of the RC locus in color-metallicity-luminosity space allows us to assign distances to the stars with an accuracy of 5%-10%. The sample extends to typical distances of about 3 kpc from the Sun, with some stars out to 8 kpc, and spans a volume of approximately 100 kpc{sup 3} over 5 kpc ≲ R ≲ 14 kpc, |Z| ≲ 2 kpc, and –15° ≲ Galactocentric azimuth ≲ 30°. The APOGEE red-clump (APOGEE-RC) catalog contains photometry from the Two Micron All Sky Survey, reddening estimates, distances, line-of-sight velocities, stellar parameters and elemental abundances determined from the high-resolution APOGEE spectra, and matches to major proper motion catalogs. We determine the survey selection function for this data set and discuss howmore » the RC selection samples the underlying stellar populations. We use this sample to limit any azimuthal variations in the median metallicity within the ≈45° azimuthal region covered by the current sample to be ≤0.02 dex, which is more than an order of magnitude smaller than the radial metallicity gradient. This result constrains coherent non-axisymmetric flows within a few kiloparsecs from the Sun.« less

Scaling macroscopic aquatic locomotion

Abstract: Nonlinear inertial flows usually influence the motion of swimming organisms, but most studies focus on the tractable case of swimmers too small to feel such effects. A mechanistic principle now unifies the varied dynamics of macroscopic swimmers. Inertial aquatic swimmers that use undulatory gaits range in length L from a few millimetres to 30 metres, across a wide array of biological taxa. Using elementary hydrodynamic arguments, we uncover a unifying mechanistic principle characterizing their locomotion by deriving a scaling relation that links swimming speed U to body kinematics (tail beat amplitude A and frequency ω) and fluid properties (kinematic viscosity ν). This principle can be simply couched as the power law Re ∼ Swα, where Re = UL/ν ≫ 1 and Sw = ω AL/ν, with α = 4/3 for laminar flows, and α = 1 for turbulent flows. Existing data from over 1,000 measurements on fish, amphibians, larvae, reptiles, mammals and birds, as well as direct numerical simulations are consistent with our scaling. We interpret our results as the consequence of the convergence of aquatic gaits to the performance limits imposed by hydrodynamics.

The Gaia-ESO Survey: the Galactic thick to thin disc transition

Abstract: Aims. The nature of the thick disc and its relation to the thin disc is presently an important subject of debate. In fact, the structural and chemo-dynamical transition between disc populations can be used as a test of the proposed models of Galactic disc formation and evolution. Methods. We used the atmospheric parameters, [alpha/Fe] abundances, and radial velocities, which were determined from the Gaia-ESO Survey GIRAFFE spectra of FGK-type stars (first nine months of observations) to provide a chemo-kinematical characterisation of the disc stellar populations. We focussed on a subsample of 1016 stars with high-quality parameters, covering the volume vertical bar Z vertical bar < 4.5 kpc and R in the range 2-13 kpc. Results. We have identified a thin to thick disc separation in the [alpha/Fe] vs. [M/H] plane, thanks to the presence of a low-density region in the number density distribution. The thick disc stars seem to lie in progressively thinner layers above the Galactic plane, as metallicity increases and [alpha/Fe] decreases. In contrast, the thin disc population presents a constant value of the mean distance to the Galactic plane at all metallicities. In addition, our data confirm the already known correlations between V-phi and [M/H] for the two discs. For the thick disc sequence, a study of the possible contamination by thin disc stars suggests a gradient up to 64 +/- 9 km s(-1) dex(-1). The distributions of azimuthal velocity, vertical velocity, and orbital parameters are also analysed for the chemically separated samples. Concerning the gradients with galactocentric radius, we find, for the thin disc, a flat behaviour of the azimuthal velocity, a metallicity gradient equal to -0.058 +/- 0.008 dex kpc(-1) and a very small positive [alpha/Fe] gradient. For the thick disc, flat gradients in [M/H] and [alpha/Fe] are derived. Conclusions. Our chemo-kinematical analysis suggests a picture where the thick disc seems to have experienced a settling process, during which its rotation increased progressively and, possibly, the azimuthal velocity dispersion decreased. At [M/H] approximate to -0.25 dex and [alpha/Fe] approximate to 0.1 dex, the mean characteristics of the thick disc in vertical distance to the Galactic plane, rotation, rotational dispersion, and stellar orbits' eccentricity agree with that of the thin disc stars of the same metallicity, suggesting a possible connection between these two populations at a certain epoch of the disc evolution. Finally, the results presented here, based only on the first months of the Gaia-ESO Survey observations, confirm how crucial large high-resolution spectroscopic surveys outside the solar neighbourhood are today for our understanding of the Milky Way history.

The Gaia-ESO Survey : radial metallicity gradients and age-metallicity relation of stars in the Milky Way disk

Abstract: We study the relationship between age, metallicity, and alpha-enhancement of FGK stars in the Galactic disk. The results are based upon the analysis of high-resolution UVES spectra from the Gaia-ESO large stellar survey. We explore the limitations of the observed dataset, i.e. the accuracy of stellar parameters and the selection effects that are caused by the photometric target preselection. We find that the colour and magnitude cuts in the survey suppress old metal-rich stars and young metal-poor stars. This suppression may be as high as 97% in some regions of the age-metallicity relationship. The dataset consists of 144 stars with a wide range of ages from 0.5 Gyr to 13.5 Gyr, Galactocentric distances from 6 kpc to 9.5 kpc, and vertical distances from the plane 0 9 Gyr is not as small as advocated by some other studies. In agreement with earlier work, we find that radial abundance gradients change as a function of vertical distance from the plane. The [Mg/Fe] gradient steepens and becomes negative. In addition, we show that the inner disk is not only more alpha-rich compared to the outer disk, but also older, as traced independently by the ages and Mg abundances of stars.

Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study

Abstract: The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs). 1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898). According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p < 0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001).

The Open Latarjet Procedure Is More Reliable in Terms of Shoulder Stability Than Arthroscopic Bankart Repair

Abstract: Background Arthroscopic Bankart repair and open Latarjet bone block procedure are widely considered mainstays for surgical treatment of recurrent anterior shoulder instability. The choice between these procedures depends mainly on surgeon preference or training rather than published evidence.

Browning of White Adipose Cells by Intermediate Metabolites:An Adaptive Mechanism to Alleviate Redox Pressure

Abstract: The presence of brown adipose tissue (BAT) in human adults opens attractive perspectives to treat metabolic disorders. Indeed, BAT dissipates energy as heat via uncoupling protein (UCP)1. Brown adipocytes are located in specific deposits or can emerge among white fat through the so-called browning process. Although numerous inducers have been shown to drive this process, no study has investigated whether it could be controlled by specific metabolites. Here, we show that lactate, an important metabolic intermediate, induces browning of murine white adipose cells with expression of functional UCP1. Lactate-induced browning also occurs in human cells and in vivo. Lactate controls Ucp1 expression independently of hypoxia-inducible factor-1α and PPARα pathways but requires active PPARγ signaling. We demonstrate that the lactate effect on Ucp1 is mediated by intracellular redox modifications as a result of lactate transport through monocarboxylate transporters. Further, the ketone body β-hydroxybutyrate, another metabolite that impacts redox state, is also a strong browning inducer. Because this redox-dependent increase in Ucp1 expression promotes an oxidative phenotype with mitochondria, browning appears as an adaptive mechanism to alleviate redox pressure. Our findings open new perspectives for the control of adipose tissue browning and its physiological relevance.