Widespread Frequent Methane Emissions From the Oil and Gas Industry in the Permian Basin.

Emissions of methane (CH4) in the Permian basin (USA) have been derived for 2019 and 2020 from satellite observations of the Tropospheric Monitoring Instrument (TROPOMI) using the divergence method, in combination with a data driven method to estimate the background column densities. The resulting CH4 emission data, which have been verified using model data with known emissions, have a spatial resolution of approximately 10 km. The CH4 emissions show moderate spatial correlation with the locations of oil and gas production and drilling activities in the Permian basin, as well as with emissions of nitrogen oxides (NOx). Analysis of the emission maps and time series indicates that a significant fraction of methane emissions in the Permian basin is from frequent widespread emissions sources, rather than from a few infrequent very large unplanned releases, which is important considering possible CH4 emission mitigation strategies. In addition to providing spatially resolved emissions, the divergence method also provides the total emissions of the Permian basin and its main sub-basins. The total CH4 emission of the Permian is estimated as 3.0 ± 0.7 Tg yr-1 for 2019, which agrees with other independent estimates based on TROPOMI data. For the Delaware sub-basin, it is estimated as 1.4 ± 0.3 Tg yr-1 for 2019, and for the Midland sub-basin 1.2 ± 0.3 Tg yr-1. In 2020 the emissions are 9% lower compared to 2019 in the entire Permian basin, and respectively 19% and 27% for the Delaware and Midland sub-basins.

Towards a classification of bifurcations in Vlasov equations.

We propose a classification of bifurcations of Vlasov equations, based on the strength of the resonance between the unstable mode and the continuous spectrum on the imaginary axis. We then identify and characterize a new type of generic bifurcation where this resonance is weak, but the unstable mode couples with a stable mode and a Casimir invariant of the system to form a size-3 Jordan block. We derive a three-dimensional reduced noncanonical Hamiltonian system describing this bifurcation. Comparison of the reduced dynamics with direct numerical simulations on a test case gives excellent agreement. We finally discuss the relevance of this bifurcation to specific physical situations.

Balance of Emission and Dynamical Controls on Ozone During the Korea-United States Air Quality Campaign From Multiconstituent Satellite Data Assimilation.

Global multiconstituent concentration and emission fields obtained from the assimilation of the satellite retrievals of ozone, CO, NO2, HNO3, and SO2 from the Ozone Monitoring Instrument (OMI), Global Ozone Monitoring Experiment 2, Measurements of Pollution in the Troposphere, Microwave Limb Sounder, and Atmospheric Infrared Sounder (AIRS)/OMI are used to understand the processes controlling air pollution during the Korea-United States Air Quality (KORUS-AQ) campaign. Estimated emissions in South Korea were 0.42 Tg N for NO x and 1.1 Tg CO for CO, which were 40% and 83% higher, respectively, than the a priori bottom-up inventories, and increased mean ozone concentration by up to 7.5 ± 1.6 ppbv. The observed boundary layer ozone exceeded 90 ppbv over Seoul under stagnant phases, whereas it was approximately 60 ppbv during dynamical conditions given equivalent emissions. Chemical reanalysis showed that mean ozone concentration was persistently higher over Seoul (75.10 ± 7.6 ppbv) than the broader KORUS-AQ domain (70.5 ± 9.2 ppbv) at 700 hPa. Large bias reductions (>75%) in the free tropospheric OH show that multiple-species assimilation is critical for balanced tropospheric chemistry analysis and emissions. The assimilation performance was dependent on the particular phase. While the evaluation of data assimilation fields shows an improved agreement with aircraft measurements in ozone (to less than 5 ppbv biases), CO, NO2, SO2, PAN, and OH profiles, lower tropospheric ozone analysis error was largest at stagnant conditions, whereas the model errors were mostly removed by data assimilation under dynamic weather conditions. Assimilation of new AIRS/OMI ozone profiles allowed for additional error reductions, especially under dynamic weather conditions. Our results show the important balance of dynamics and emissions both on pollution and the chemical assimilation system performance.

Mercury Isotopic Fractionation during Pedogenesis in a Tropical Forest Soil Catena (French Guiana): Deciphering the Impact of Historical Gold Mining.

We used natural mercury (Hg) stable isotopes to investigate the Hg cycle in a rainforest soil catena (French Guiana) partially gold-mined during the early 1950s. Litterfall showed homogeneous Δ199Hg values [-0.18 ± 0.05‰, i.e., a modern gaseous elemental Hg (GEM) isotopic signature]. After litter decomposition, Hg bound to organic matter (OM) is mixed with Hg from pristine (-0.55 ± 0.22‰) or gold-mined (-0.09 ± 0.16‰) mineral materials. Negative Δ199Hg values in deep pristine mineral horizons (-0.60 ± 0.16‰) suggest the transfer of Hg bound to dissolved OM depleted in odd isotopes due to mass-independent fractionation during Hg abiotic reduction. Perennial palm tree leaves collected above gold-mined and pristine soil recorded contrasting Δ199Hg signatures likely resulting from GEM re-emission processes from soils and leaf surfaces. Upslope, soil δ202Hg signatures showed a negative shift (ε ∼ -1‰) with depth attributed to mass-dependent fractionation during Hg sorption and complexation onto iron oxides and dissolved OM. Downslope, higher δ202Hg values in soils resulted from hydromorphy [lower humification, greater Hg(II) reduction, etc.]. The unique Hg isotopic signatures of Amazonian soils probably result in multistep fractionation processes during pedogenesis (millions of years) and in a potentially different Hg isotopic signature of preanthropogenic background GEM.

Particle Interactions Mediated by Dynamical Networks: Assessment of Macroscopic Descriptions.

We provide a numerical study of the macroscopic model of Barré et al. (Multiscale Model Simul, 2017, to appear) derived from an agent-based model for a system of particles interacting through a dynamical network of links. Assuming that the network remodeling process is very fast, the macroscopic model takes the form of a single aggregation-diffusion equation for the density of particles. The theoretical study of the macroscopic model gives precise criteria for the phase transitions of the steady states, and in the one-dimensional case, we show numerically that the stationary solutions of the microscopic model undergo the same phase transitions and bifurcation types as the macroscopic model. In the two-dimensional case, we show that the numerical simulations of the macroscopic model are in excellent agreement with the predicted theoretical values. This study provides a partial validation of the formal derivation of the macroscopic model from a microscopic formulation and shows that the former is a consistent approximation of an underlying particle dynamics, making it a powerful tool for the modeling of dynamical networks at a large scale.

Bifurcations and Singularities for Coupled Oscillators with Inertia and Frustration.

We prove that any nonzero inertia, however small, is able to change the nature of the synchronization transition in Kuramoto-like models, either from continuous to discontinuous or from discontinuous to continuous. This result is obtained through an unstable manifold expansion in the spirit of Crawford, which features singularities in the vicinity of the bifurcation. Far from being unwanted artifacts, these singularities actually control the qualitative behavior of the system. Our numerical tests fully support this picture.

Trapping scaling for bifurcations in the Vlasov systems.

We study nonoscillating bifurcations of nonhomogeneous steady states of the Vlasov equation, a situation occurring in galactic models, or for Bernstein-Greene-Kruskal modes in plasma physics. Through an unstable manifold expansion, we show that in one spatial dimension the dynamics is very sensitive to the initial perturbation: the instability may saturate at small amplitude-generalizing the "trapping scaling" of plasma physics-or may grow to produce a large-scale modification of the system. Furthermore, resonances are strongly suppressed, leading to different phenomena with respect to the homogeneous case. These analytical findings are illustrated and extended by direct numerical simulations with a cosine interaction potential.

Nonequilibrium phase transition with gravitational-like interaction in a cloud of cold atoms.

We propose to use a cloud of laser-cooled atoms in a quasi-two-dimensional trap to investigate a nonequilibrium collapse phase transition in the presence of a gravitational-like interaction. Using theoretical arguments and numerical simulations, we show that, like in two-dimensional gravity, a transition to a collapsed state occurs below a critical temperature. In addition and as a signature of the nonequilibrium nature of the system, persistent particle currents, dramatically increasing close to the phase transition, are observed.

The cost of headache disorders in Europe: the Eurolight project.

BACKGROUND AND PURPOSE: Headache disorders are very common, but their monetary costs in Europe are unknown. We performed the first comprehensive estimation of how economic resources are lost to headache in Europe. METHODS: From November 2008 to August 2009, a cross-sectional survey was conducted in eight countries representing 55% of the adult EU population. Participation rates varied between 11% and 59%. In total, 8412 questionnaires contributed to this analysis. Using bottom-up methodology, we estimated direct (medications, outpatient health care, hospitalization and investigations) and indirect (work absenteeism and reduced productivity at work) annual per-person costs. Prevalence data, simultaneously collected and, for migraine, also derived from a systematic review, were used to impute national costs. RESULTS: Mean per-person annual costs were €1222 for migraine (95% CI 1055-1389; indirect costs 93%), €303 for tension-type headache (TTH, 95% CI 230-376; indirect costs 92%), €3561 for medication-overuse headache (MOH, 95% CI 2487-4635; indirect costs 92%), and €253 for other headaches (95% CI 99-407; indirect costs 82%). In the EU, the total annual cost of headache amongst adults aged 18-65 years was calculated, according to our prevalence estimates, at €173 billion, apportioned to migraine (€111 billion; 64%), TTH (€21 billion; 12%), MOH (€37 billion; 21%) and other headaches (€3 billion; 2%). Using the 15% systematic review prevalence of migraine, calculated costs were somewhat lower (migraine €50 billion, all headache €112 billion annually). CONCLUSIONS: Headache disorders are prominent health-related drivers of immense economic losses for the EU. This has immediate implications for healthcare policy. Health care for headache can be both improved and cost saving.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

The Eurolight project: the impact of primary headache disorders in Europe. Description of methods.

The Eurolight project is the first at European Union level to assess the impact of headache disorders, and also the first of its scale performed by collaboration between professional and lay organizations and individuals. Here are reported the methods developed for it. The project took the form of surveys, by structured questionnaire, conducted in ten countries of Europe which together represented 60% of the adult population of the European Union. In Lithuania, the survey was population-based. Elsewhere, truly population-based studies were impractical for reasons of cost, and various compromises were developed. Closest to being population-based were the surveys in Germany, Luxembourg, the Netherlands, Italy and Spain. In Austria, France and UK, samples were taken from health-care settings. In addition in the Netherlands, Spain and Ireland, samples were drawn from members of national headache patient organizations and their relatives. Independent double data-entry was performed prior to analysis. Returned questionnaires from 9,269 respondents showed a moderate female bias (58%); of respondents from patients' organizations (n = 992), 61% were female. Mean age of all respondents was 44 years; samples from patients' organizations were slightly older (mean 47 years). The different sampling methods worked with differing degrees of effectiveness, as evidenced by the responder-rates, which varied from 10.8 to 90.7%. In the more population-based surveys, responder-rates varied from 11.3 to 58.8%. We conclude that the methodology, although with differences born of necessity in the ten countries, was sound overall, and will provide robust data on the public ill-health that results from headache in Europe.

Can oral vitamin K before elective surgery substitute for preoperative heparin bridging in patients on vitamin K antagonists?

BACKGROUND: After a vitamin K antagonist (VKA) overdose, 1-2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range. OBJECTIVE: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to < or = 1.5 before elective surgery. METHODS: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day -5 before surgery (group H) or to VKA treatment until day -2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days -5/-2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC). RESULTS: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days -1 and 0 than in group H. An INR < or = 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients. CONCLUSIONS: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants.

Stealth nanoparticles coated with heparin as peptide or protein carriers.

Nanoparticles (prepared from a mixture of polyester and a polycationic polymer) loaded with insulin were prepared by a double emulsion method followed by evaporation solvent. Low molecular weight heparin (LMWH) was bound by electrostatic interactions onto the surface of the particles to confer Stealth properties. These nanoparticles were characterized in vitro (mean diameter, zeta potential, encapsulation efficiency, and release kinetics) and compared with conventional (without LMWH) and unloaded nanoparticles. The pharmacokinetics of insulin were studied after intravenous injection into diabetic rats in the form of Stealth or conventional nanoparticles or as a solution. Stealth nanoparticles allowed an increase in the elimination half-life of insulin, showing that the hydrophilic layer of LMWH was able to limit recognition by the mononuclear phagocytosis system in vivo. However, complement activation studies (CH50) did not reveal significant difference between Stealth and conventional nanoparticles.

Hierarchical models of rigidity percolation.

We introduce models of generic rigidity percolation in two dimensions on hierarchical networks and solve them exactly by means of a renormalization transformation. We then study how the possibility for the network to self organize in order to avoid stressed bonds may change the phase diagram. In contrast to what happens on random graphs and in some recent numerical studies at zero temperature, we do not find a true intermediate phase separating the usual rigid and floppy ones.

Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study.

BACKGROUND: In view of recent substantial changes in the management of orthopedic surgery patients, a study was performed in order to update data on the epidemiology of venous thromboembolism (VTE) in patients undergoing lower limb arthroplasty according to contemporary practise. METHODS: We performed a prospective observational study of a cohort of consecutive patients hospitalized for total hip or knee replacement in June 2003. The primary study outcome was the incidence of symptomatic VTE at 3 months. All events were adjudicated by an independent critical event committee. RESULTS: Data from 1080 patients (mean age 68.0 years) were available; 63.2% were undergoing total hip replacement and 36.8% total knee replacement. Pharmacological thromboprophylaxis was administered for a mean time of 36 days. Injectable antithrombotics were used in more than 99% of patients, irrespective of the type of surgery. The incidence of the primary study outcome was 1.8% (20 events; 95% CI: 1.0-2.6%). The incidences were 1.3% and 2.8% in hip and knee surgery patients, respectively. There were two pulmonary embolisms, both in knee surgery patients; neither was fatal. Thirty-five per cent of VTEs occurred after hospital discharge. An age of at least 75 years and the absence of ambulation before hospital discharge were the only significant (P < 0.05) predictors of VTE. The rate of clinically significant bleeding was 1.0% and the rate of death was 0.9%. CONCLUSIONS: The incidence of symptomatic VTE after lower limb arthroplasty is low, even if there is still a need to improve thromboprophylaxis, notably in patients undergoing knee arthroplasty.

[A study of action planning in patients with Alzheimer's disease using the zoo map test]. / Etude de la planification de l'action au moyen du test du plan du zoo dans la maladie d'Alzheimer.

INTRODUCTION: Executive dysfunction is regularly reported in patients with Alzheimer's disease. Nevertheless few studies have focused on planning ability in this neurodegenerative disease. OBJECTIVES: This study aimed to investigate the formulation and the execution of plans in Alzheimer's disease using an ecological planning subtask derived from the Behavioural Assessment of the Dysexecutive Syndrome test battery, the "Zoo Map Test". There are two trials. The first trial consists of a "high demand" version of the subtask in which the subjects must plan in advance the order in which they will visit designated locations in a zoo (formulation level). In the second, or "low demand" version, the subject is simply required to follow a concrete externally imposed strategy to reach the locations to visit (execution level). The test was given to 16 patients with Alzheimer's disease and 13 normal elderly subjects. RESULTS: The two way ANOVAs mainly showed more difficulties in patients with Alzheimer's disease than in healthy elderly in both conditions. The difference between formulation and execution was greater in patients with Alzheimer's disease than in healthy elderly. Planning impairments mainly correlated with behavioural changes (in particular motivational changes) observed by patient's relatives. CONCLUSION: These results suggest that patients with Alzheimer's disease have some problems to mentally develop logical strategies and to execute complex predetermined plans, which are partially related to behavioural changes.

Time scale for magnetic reversal and the topological nonconnectivity threshold.

Anisotropic classical Heisenberg models with all-to-all spin coupling display a topological nonconnectivity threshold (TNT) for any number N of spins. Below this threshold, the energy surface is disconnected in two components with positive and negative total magnetizations, respectively, so that magnetization cannot reverse its sign and ergodicity is broken, even at finite N. Here, we solve the model in the microcanonical ensemble, using a recently developed method based on large deviation techniques, and show that a phase transition is present at an energy higher than the TNT energy. In the energy range between the TNT energy and the phase transition, magnetization changes sign stochastically and its behavior can be fully characterized by an average magnetization reversal time. The time scale for magnetic reversal can be computed analytically, using statistical mechanics. Numerical simulations confirm this calculation and further show that the magnetic reversal time diverges with a power law at the TNT threshold, with a size-dependent exponent. This exponent can be computed in the thermodynamic limit N-->(infinity), by the knowledge of entropy as a function of magnetization, and turns out to be in reasonable agreement with finite numerical simulations. We finally generalize our results to other models: Heisenberg chains with distance-dependent coupling, small 3D clusters with nearest-neighbor interactions, metastable states. We conjecture that the power-law divergence of the magnetic reversal time scale might be a universal signature of the presence of a TNT.

Adaptability and "intermediate phase" in randomly connected networks.

We present a simple model that enables us to analytically characterize a floppy to rigid transition and an associated self-adaptive intermediate phase in a random bond network. In this intermediate phase, the network adapts itself to lower the stress due to constraints. Our simulations verify this picture. We use these insights to identify applications of these ideas in computational problems such as vertex cover and K-satisfiability.

[Drug registration file prerequisites for European procedures]. / Le dossier pharmacocinétique des médicaments requis dans les procédures européennes.

The pharmacokinetic content of the drug registration file is now well standardized. The objectives of the pharmacokinetic documentation is to provide evidence supporting the dosing regimen in patients, to take into account the pathophysiological states of the populations at risk and to anticipate drug-drug interactions. Recommendations on study design and evaluation of parameters of interest are listed in various documents Issued by the Committee for Proprietary Medicinal Products and the International conferences on Harmonization, i.e. the Concept Papers, the Points to Consider and Notes for Guidance. The pharmacokinetic data of the registration file are used to document many sections of the Summary of the Product Characteristics.

Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime--a population study in 25 elderly patients.

OBJECTIVE: To develop a pharmacostatistical model to simultaneously characterise the pharmacokinetics of cefotaxime and its main metabolite, desacetylcefotaxime, in elderly patients. METHODS: Cefotaxime, 1 g, was infused three times daily to 25 elderly patients, 66-93 years old. Cefotaxime and desacetylcefotaxime plasma concentrations (289 and 304 samples, respectively), along with demographic and physiological characteristics, were analysed using a population approach. RESULTS: Cefotaxime pharmacokinetics was best described by a two-compartment open model in which desacetylcefotaxime was produced from the central compartment. The final parameter estimates were derived from simultaneous fit of parent/metabolite data. Cefotaxime clearance, mean 5.5 l/h, was positively influenced by body weight and serum protein concentration and negatively influenced by serum creatinine and age. In contrast, desacetylcefotaxime elimination was only decreased by age. The mean terminal half-lives of cefotaxime and desacetylcefotaxime were 1.7 h and 2.6 h, respectively. The stability and predictive performance of the final population pharmacokinetic model was assessed using 200 bootstrap samples of the original data. CONCLUSION: Cefotaxime and desacetylcefotaxime elimination decreased with increasing age above 60 years. This decreased elimination was related to individual characteristics that are typically related to renal function.