Showing papers by "University of Bordeaux published in 2017"

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Abstract: Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria

Abstract: Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence.

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma

Abstract: BackgroundCombination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. MethodsIn this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis–free survival, freedom from relapse, and safety. ResultsAt a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group a...

The challenge of mapping the human connectome based on diffusion tractography

Abstract: Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

Abstract: BackgroundTrials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. MethodsIn a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison o...

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Methodological Guidelines to Study Extracellular Vesicles.

Abstract: Owing to the relationship between extracellular vesicles (EVs) and physiological and pathological conditions, the interest in EVs is exponentially growing. EVs hold high hopes for novel diagnostic and translational discoveries. This review provides an expert-based update of recent advances in the methods to study EVs and summarizes currently accepted considerations and recommendations from sample collection to isolation, detection, and characterization of EVs. Common misconceptions and methodological pitfalls are highlighted. Although EVs are found in all body fluids, in this review, we will focus on EVs from human blood, not only our most complex but also the most interesting body fluid for cardiovascular research.

[Epidemiology of age-related macular degeneration].

Abstract: Epidemiology of age-related macular degeneration. The epidemiological studies conducted in the last 30 years have allowed the estimation of the prevalence of age-related macular degeneration (AMD) on the different continents, and the identification of its main risk factors. Thus, the prevalence of AMD increases strongly with age and is more frequent in populations of European ancestry than in those of African ancestry, with an intermediate situation in Asians and Hispanics. More than 50 genetic polymorphisms have been identified as associated with AMD, including 2 major associations with the complement factor H (CFH) and ARMS2 genes. Smoking is a major risk factor, with a 5-fold increased risk in heavy smokers. Finally, the role of nutrition (in particular intakes of antioxidants, lutein and zeaxanthin and omega 3 fatty acids) appears important. The major role played by modifiable factors (in particular smoking and nutrition) opens the way to preventive strategies.

Estimation of extended mixed models using latent classes and latent processes: The R package lcmm

Abstract: The R package lcmm provides a series of functions to estimate statistical models based on linear mixed model theory. It includes the estimation of mixed models and latent class mixed models for Gaussian longitudinal outcomes (hlme), curvilinear and ordinal univariate longitudinal outcomes (lcmm) and curvilinear multivariate outcomes (multlcmm), as well as joint latent class mixed models (Jointlcmm) for a (Gaussian or curvilinear) longitudinal outcome and a time-to-event outcome that can be possibly left-truncated right-censored and defined in a competing setting. Maximum likelihood esimators are obtained using a modified Marquardt algorithm with strict convergence criteria based on the parameters and likelihood stability, and on the negativity of the second derivatives. The package also provides various post-fit functions including goodness-of-fit analyses, classification, plots, predicted trajectories, individual dynamic prediction of the event and predictive accuracy assessment. This paper constitutes a companion paper to the package by introducing each family of models, the estimation technique, some implementation details and giving examples through a dataset on cognitive aging.

Forest biodiversity, ecosystem functioning and the provision of ecosystem services

Abstract: Forests are critical habitats for biodiversity and they are also essential for the provision of a wide range of ecosystem services that are important to human well-being. There is increasing evidence that biodiversity contributes to forest ecosystem functioning and the provision of ecosystem services. Here we provide a review of forest ecosystem services including biomass production, habitat provisioning services, pollination, seed dispersal, resistance to wind storms, fire regulation and mitigation, pest regulation of native and invading insects, carbon sequestration, and cultural ecosystem services, in relation to forest type, structure and diversity. We also consider relationships between forest biodiversity and multifunctionality, and trade-offs among ecosystem services. We compare the concepts of ecosystem processes, functions and services to clarify their definitions. Our review of published studies indicates a lack of empirical studies that establish quantitative and causal relationships between forest biodiversity and many important ecosystem services. The literature is highly skewed; studies on provisioning of nutrition and energy, and on cultural services, delivered by mixed-species forests are under-represented. Planted forests offer ample opportunity for optimising their composition and diversity because replanting after harvesting is a recurring process. Planting mixed-species forests should be given more consideration as they are likely to provide a wider range of ecosystem services within the forest and for adjacent land uses. This review also serves as the introduction to this special issue of Biodiversity and Conservation on various aspects of forest biodiversity and ecosystem services.

Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis.

Abstract: PurposeLenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting.Patients and MethodsThe meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myelome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for pri...

Learning through ferroelectric domain dynamics in solid-state synapses.

Abstract: In the brain, learning is achieved through the ability of synapses to reconfigure the strength by which they connect neurons (synaptic plasticity). In promising solid-state synapses called memristors, conductance can be finely tuned by voltage pulses and set to evolve according to a biological learning rule called spike-timing-dependent plasticity (STDP). Future neuromorphic architectures will comprise billions of such nanosynapses, which require a clear understanding of the physical mechanisms responsible for plasticity. Here we report on synapses based on ferroelectric tunnel junctions and show that STDP can be harnessed from inhomogeneous polarization switching. Through combined scanning probe imaging, electrical transport and atomic-scale molecular dynamics, we demonstrate that conductance variations can be modelled by the nucleation-dominated reversal of domains. Based on this physical model, our simulations show that arrays of ferroelectric nanosynapses can autonomously learn to recognize patterns in a predictable way, opening the path towards unsupervised learning in spiking neural networks.

The national healthcare system claims databases in France, SNIIRAM and EGB: Powerful tools for pharmacoepidemiology.

Abstract: The French health care system is based on universal coverage by one of several health care insurance plans. The SNIIRAM database merges anonymous information of reimbursed claims from all these plans, linked to the national hospital-discharge summaries database system (PMSI) and the national death registry. It now covers 98.8% of the French population, over 66 million persons, from birth (or immigration) to death (or emigration), making it possibly the world's largest continuous homogeneous claims database. The database includes demographic data; health care encounters such as physician or paramedical visits, medicines, medical devices, and lab tests (without results); chronic medical conditions (ICD10 codes); hospitalisations with ICD10 codes for primary, linked and associated diagnoses, date and duration, procedures, diagnostic-related groups, and cost coding; date but currently not cause of death. The power of the database is correlatively great, and its representativeness is near perfect, since it essentially includes the whole country's population. The main difficulty in using the database, beyond its sheer size and complexity, is the administrative process necessary to access it. Recent legislative advances are making this easier. EGB (Echantillon Generaliste de Beneficiaires) is the 1/97th random permanent representative sample of SNIIRAM, with planned 20-year longitudinal data (10 years at this time). Access time is 1 to 3 months, but its power is less (780 000 subjects). This is enough to study common issues with older drugs but may be limited for new products or rare events.

The age of the hominin fossils from Jebel Irhoud, Morocco, and the origins of the Middle Stone Age

Abstract: The timing and location of the emergence of our species and of associated behavioural changes are crucial for our understanding of human evolution. The earliest fossil attributed to a modern form of Homo sapiens comes from eastern Africa and is approximately 195 thousand years old, therefore the emergence of modern human biology is commonly placed at around 200 thousand years ago. The earliest Middle Stone Age assemblages come from eastern and southern Africa but date much earlier. Here we report the ages, determined by thermoluminescence dating, of fire-heated flint artefacts obtained from new excavations at the Middle Stone Age site of Jebel Irhoud, Morocco, which are directly associated with newly discovered remains of H. sapiens. A weighted average age places these Middle Stone Age artefacts and fossils at 315 ± 34 thousand years ago. Support is obtained through the recalculated uranium series with electron spin resonance date of 286 ± 32 thousand years ago for a tooth from the Irhoud 3 hominin mandible. These ages are also consistent with the faunal and microfaunal assemblages and almost double the previous age estimates for the lower part of the deposits. The north African site of Jebel Irhoud contains one of the earliest directly dated Middle Stone Age assemblages, and its associated human remains are the oldest reported for H. sapiens. The emergence of our species and of the Middle Stone Age appear to be close in time, and these data suggest a larger scale, potentially pan-African, origin for both.

Historic global biomass burning emissions for CMIP6 (BB4CMIP) based on merging satellite observations with proxies and fire models (1750-2015)

Abstract: Fires have influenced atmospheric composition and climate since the rise of vascular plants, and satellite data have shown the overall global extent of fires. Our knowledge of historic fire emissions has progressively improved over the past decades due mostly to the development of new proxies and the improvement of fire models. Currently, there is a suite of proxies including sedimentary charcoal records, measurements of fire-emitted trace gases and black carbon stored in ice and firn, and visibility observations. These proxies provide opportunities to extrapolate emission estimates back in time based on satellite data starting in 1997, but each proxy has strengths and weaknesses regarding, for example, the spatial and temporal extents over which they are representative. We developed a new historic biomass burning emissions dataset starting in 1750 that merges the satellite record with several existing proxies and uses the average of six models from the Fire Model Intercomparison Project (FireMIP) protocol to estimate emissions when the available proxies had limited coverage. According to our approach, global biomass burning emissions were relatively constant, with 10-year averages varying between 1.8 and 2.3 PgC yr-1. Carbon emissions increased only slightly over the full time period and peaked during the 1990s after which they decreased gradually. There is substantial uncertainty in these estimates, and patterns varied depending on choices regarding data representation, especially on regional scales. The observed pattern in fire carbon emissions is for a large part driven by African fires, which accounted for 58% of global fire carbon emissions. African fire emissions declined since about 1950 due to conversion of savanna to cropland, and this decrease is partially compensated for by increasing emissions in deforestation zones of South America and Asia. These global fire emission estimates are mostly suited for global analyses and will be used in the Coupled Model Intercomparison Project Phase 6 (CMIP6) simulations.

3FHL: The Third Catalog of Hard Fermi-LAT Sources

Abstract: We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard Fermi-LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV–2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift (z > 2). Eight percent of the sources have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 ×10 −11 ph cm −2 s −1 , respectively (this is approximately 0.5 % and 1 % of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ-ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10 −12 erg cm −2 s −1 , the energy range above 10 GeV has twice as many sources as above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.

Hydrolysis of Ammonia-Borane over Ni/ZIF-8 Nanocatalyst: High Efficiency, Mechanism, and Controlled Hydrogen Release

Abstract: Non-noble metal nanoparticles are notoriously difficult to prepare and stabilize with appropriate dispersion, which in turn severely limits their catalytic functions. Here, using zeolitic imidazolate framework (ZIF-8) as MOF template, catalytically remarkably efficient ligand-free first-row late transition-metal nanoparticles are prepared and compared. Upon scrutiny of the catalytic principles in the hydrolysis of ammonia-borane, the highest total turnover frequency among these first-row late transition metals is achieved for the templated Ni nanoparticles with 85.7 molH2 molcat–1 min–1 at room temperature, which overtakes performances of previous non-noble metal nanoparticles systems, and is even better than some noble metal nanoparticles systems. Mechanistic studies especially using kinetic isotope effects show that cleavage by oxidative addition of an O–H bond in H2O is the rate-determining step in this reaction. Inspired by these mechanistic studies, an attractive and effective “on–off” control of hyd...

In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for in vivo bone regeneration applications.

Abstract: Bioprinting has emerged as a novel technological approach with the potential to address unsolved questions in the field of tissue engineering. We have recently shown that Laser Assisted Bioprinting (LAB), due to its unprecedented cell printing resolution and precision, is an attractive tool for the in situ printing of a bone substitute. Here, we show that LAB can be used for the in situ printing of mesenchymal stromal cells, associated with collagen and nano-hydroxyapatite, in order to favor bone regeneration, in a calvaria defect model in mice. Also, by testing different cell printing geometries, we show that different cellular arrangements impact on bone tissue regeneration. This work opens new avenues on the development of novel strategies, using in situ bioprinting, for the building of tissues, from the ground up.

A seven-planet resonant chain in TRAPPIST-1

Abstract: The TRAPPIST-1 system is the first transiting planet system found orbiting an ultra-cool dwarf star. At least seven planets similar to Earth in radius and in mass were previously found to transit this host star. Subsequently, TRAPPIST-1 was observed as part of the K2 mission and, with these new data, we report the measurement of an 18.764 d orbital period for the outermost planet, TRAPPIST-1h, which was unconstrained until now. This value matches our theoretical expectations based on Laplace relations and places TRAPPIST-1h as the seventh member of a complex chain, with three-body resonances linking every member. We find that TRAPPIST-1h has a radius of 0.715 Earth radii and an equilibrium temperature of 169 K, placing it at the snow line. We have also measured the rotational period of the star at 3.3 d and detected a number of flares consistent with an active, middle-aged, late M dwarf.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

Abstract: Background An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). Methods Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. Key Results Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. Conclusions and Inferences The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.