New horizons for fundamental physics with LISA

The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas

Implantation Serine Proteinase 1 Exhibits Mixed Substrate Specificity that Silences Signaling via Proteinase-Activated Receptors

Implantation S1 family serine proteinases (ISPs) are tryptases involved in embryo hatching and uterine implantation in the mouse. The two different ISP proteins (ISP1 and ISP2) have been detected in both pre- and post-implantation embryo tissue. To date, native ISP obtained from uterus and blastocyst tissues has been isolated only as an active hetero-dimer that exhibits trypsin-like substrate specificity. We hypothesised that in isolation, ISP1 might have a unique substrate specificity that could relate to its role when expressed alone in individual tissues. Thus, we isolated recombinant ISP1 expressed in Pichia pastoris and evaluated its substrate specificity. Using several chromogenic substrates and serine proteinase inhibitors, we demonstrate that ISP1 exhibits trypsin-like substrate specificity, having a preference for lysine over arginine at the P1 position. Phage display peptide mimetics revealed an expanded but mixed substrate specificity of ISP1, including chymotryptic and elastase activity. Based upon targets observed using phage display, we hypothesised that ISP1 might signal to cells by cleaving and activating proteinase-activated receptors (PARs) and therefore assessed PARs 1, 2 and 4 as potential ISP1 targets. We observed that ISP1 silenced enzyme-triggered PAR signaling by receptor-disarming. This PAR-disarming action of ISP1 may be important for embryo development and implantation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Cartographie des forêts anciennes de France : objectifs, bilan et perspectives

Il y a dix ans démarraient les premiers travaux de vectorisation, à l'échelle régionale, des forêts de la carte d'Etat-Major, en vue de l'établissement d'une carte nationale des forêts à longue continuité de l'état boisé. Où en est-on aujourd'hui ? Nous faisons le point de l'avancement des travaux et en tirons les premiers enseignements, en répondant aux questions suivantes : Quels sont les définitions et concepts sous-jacents à ces travaux ? Pourquoi cartographier les forêts dites "anciennes" ou "récentes" ? L'analyse des institutions ayant réalisé le travail montre que ce sont principalement les milieux de la conservation qui ont été moteurs dans ces travaux. Mais la production et la qualité des produits bois sont aussi concernés par cette cartographie. Le rôle actuel de puits de carbone des forêts françaises ne peut par exemple se comprendre qu'au travers de cette dynamique forestière ancienne. Pourquoi une focalisation sur la première moitié du XIXe siècle comme date de référence ? Que signifie la notion de minimum forestier ? Quelles en sont les limites ? Quels sont les supports de données les plus intéressantes pour cette cartographie ? Pourquoi la carte d'Etat-Major est une source particulière d'information, dans l'objectif de la cartographie des forêts anciennes, parmi la multitude de cartes ou statistiques disponibles à différentes dates et échelles ? Quelles sont les méthodes d'acquisition de la donnée ? Quelle est la précision spatiale des cartes d'occupation du sol obtenues ? Les principaux problèmes posés par l'utilisation de la carte d'Etat-Major seront présentés, ainsi que la façon dont différents projets y ont répondu. Quels résultats ont été obtenus ? Nous reviendrons entre autres sur l'estimation de la surface forestière française à la date de son minimum. Les cartes déjà réalisées, sur 33% du territoire, permettent de dessiner avec précision et de comparer les changements d'occupation du sol dans différentes régions de France, en termes de pourcentage de déboisement, reboisement et taux de forêt ancienne dans la forêt actuelle. Les évolutions du couvert forestier issues d'autres sources non cartographiques sont-elles confirmées ? Le lien avec le type de propriété foncière est particulièrement intéressant à analyser. Dans plusieurs zones de France (Pyrénées, Luberon, Alpes, Lorraine, Nord-Pas-de-Calais...) ont été réalisés des croisements entre ces cartes et les bases de données régionales de relevés floristiques (Inventaire forestier national, conservatoires botaniques). Ce nouveau type d'analyse permet d'identifier rapidement les espèces végétales liées à la continuité de l'état boisé, dites espèces de forêts anciennes, et les traits de vie qui leur sont associés. Nous présenterons une synthèse de ces résultats. Dans la moitié des zones déjà cartographiées, ce sont toutes les occupations du sol anciennes qui ont été numérisées et non seulement les forêts. Nous évoquerons l'intérêt de ce cadastre ancien, au-delà des seules questions forestières, pour le suivi de la dynamique à long terme des prairies, des milieux humides, des vignes ou des milieux urbanisés. Les techniques de vectorisation des occupations anciennes du sol évoluent vers une simplification et une accélération qui laisse présager une fin du travail plus rapide que prévue initialement, parfois au détriment de la qualité. L'extension à la France entière permettra une vision à la fois à petite échelle mais localement précise des mouvements des masses forestières. Nous discuterons les perspectives de recherche et les développements en cours, ouverts par ces progrès

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

La Loire : fleuve ou torrent ? Expérimentation et modélisation mathématique

National audienc

Assessing the influence of the variability of soil surface characteristics on infiltration and runoff: an experimental approach in the lab

Soil surface characteristics (SSCs) are highly variable even at a small scale (< 1m2) and the infiltration-runoff partitioning under rainfall is dependent on the spatial variability and spatial structure of SSCs. For a better understanding of the influence of the variability of SSCs on infiltration-runoff partitioning, a modelling approach may be needed due to the complexity of the problem, but at the same time experiments are needed with measurements of all components of the soil water balance, namely soil water storage, drainage, soil surface detention and runoff. The aim of this paper is to describe the experimental setup and the first results of an infiltration-runoff experiment conducted in the lab under simulated rainfall on a 2D model of heterogeneous remoulded soil. A 50cm long x 10cm wide x 20 cm high model of soil with a wavy surface was first built. The wavy surface created 3 depressions of increasing depth (0.2 to 2.5 cm) from upstream to downstream. 3 pats of compacted soil were then inserted at the bottom of the depression: this model was representative for a system of sedimentary crusts and undisturbed soil. 24 micro-tensiometers were inserted to measure soil water matrix potentials every 10 s, and runoff flow was recorded at the same time step. Distributed drainage flow was manually measured. The soil model was then placed under a rainfall simulator using the facilities of the INRA Soil Science Lab in Orléans, France. Hydrodynamic properties of the un-compacted soil and compacted soil were measured with the Wind’s evaporation method. Digital Elevation Model (DEM) of the soil model was obtained at the beginning and at the end with a laser profile-meter and with a photogrammetric method. Photogrammetry was also used to estimate the amount of water stored in depressions at the soil surface. First results show the relations between the evolution in time of the depressional water storage, the runoff flow and the soil matrix potentials. This kind of experiment provides data helpful for the validation of numerical model coupling distributed soil infiltration and distributed runoff and accounting for the variability of soil hydrodynamic properties

Neutrophil elastase and proteinase-3 trigger G proteinbiased signaling through proteinase-activated receptor-1 (PAR1)

Neutrophil proteinases released at sites of inflammation can affect tissue function by either activating or disarming signal transduction mediated by proteinase-activated receptors (PARs). BecausePAR1is expressed at sites where abundant neutrophil infiltration occurs, we hypothesized that neutrophil-derived enzymes might also regulate PAR1 signaling. We report here that both neutrophil elastase and proteinase-3 cleave the human PAR1 N terminus at sites distinct from the thrombin cleavage site. This cleavage results in a disarming of thrombinactivated calcium signaling through PAR1. However, the distinct non-canonical tethered ligands unmasked by neutrophil elastase and proteinase-3, as well as synthetic peptides with sequences derived from these novel exposed tethered ligands, selectively stimulated PAR1-mediated mitogen-activated protein kinase activation. This signaling was blocked by pertussis toxin, implicating a Gαi-triggered signal pathway. We conclude that neutrophil proteinases trigger biased PAR1 signaling and we describe a novel set of tethered ligands that are distinct from the classical tethered ligand revealed by thrombin. We further demonstrate the function of this biased signaling in regulating endothelial cell barrier integrity. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc

Transfert des éléments traces métalliques par le ruissellement et l'érosion diffuse dans le vignoble champenois

National audienc

Derivatized 2-furoyl-LIGRLO-amide, a versatile and selective probe for proteinase-activated receptor 2: Binding and visualization

The proteinase-activated receptor-2 (PAR2)-activating peptide with an N-terminal furoyl group modification, 2-furoyl-LIGRLO-NH2 (2fLI), was derivatized via its free ornithine amino group to yield [ 3H]propionyl-2fLI and Alexa Fluor 594-2fLI that were used as receptor probes for ligand binding assays and receptor visualization both for cultured cells in vitro and for colonic epithelial cells in vivo. The binding of the radiolabeled and fluorescent PAR2 probes was shown to be present in PAR2-transfected Kirsten normal rat kidney cells, but not in vectoralone-transfected cells, and was abolished by pretreatment of cells with saturating concentrations of receptor-selective PAR2 peptide agonists such as SLIGRL-NH2 and the parent agonist 2fLI but not by reverse-sequence peptides such as 2-furoyl-OLRGIL-NH2 that cannot activate PAR2. The relative orders of potencies for a series of PAR2 peptide agonists to compete for the binding of [ 3H]propionyl-2fLI (2fLI ≫ SLIGRL-NH2 ≅ transcinnamoyl-LIGRLO-NH2 \u3e SLIGKV-NH2 \u3e SLIGKT-NH2) mirrored qualitatively their relative potencies for PAR2-mediated calcium signaling in the same cells or for vasorelaxation in a rat aorta vascular assay. In the vascular assay, the potency of Alexa Fluor 594-2fLI was the same as 2fLI. We conclude that ornithine-derivatized 2fLI peptides are conveniently synthesized PAR2 probes that will be of value for future studies of receptor binding and visualization. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics