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In the last 20 years many discretization schemes have been developed to approximate the Darcy fluxes on polyhedral cells in heterogeneous anisotropic porous media. Among them, we can distinguished cell based approaches like the Two Point Flux Approximation (TPFA) or the Multi Point Flux Approximation (MPFA) schemes, face based approaches like the Hybrid Finite Volume (HFV) scheme belonging to the family of Hybrid Mimetic Mixed methods and nodal based discretizations like the Vertex Approximate Gradient (VAG) scheme. They all have their own drawbacks and advantages which typically depend on the type of cells and on the anisotropy of the medium. In this work, we propose a new methodology to combine the VAG and HFV discretizations on arbitrary subsets of cells or faces in order to choose the best suited scheme in different parts of the mesh. In our approach the TPFA discretization is considered as an HFV discretization for which the face unknowns can be eliminated. The coupling strategy is based on a node to face interpolation operator at the interfaces which must be chosen to ensure the consistency, the coercivity and the limit conformity properties of the combined discretization. The convergence analysis is performed in the gradient discretization framework and convergence is proved for arbitrary cell or face partitions of the mesh. For face partitions, an additional stabilisation local to the cell is required to ensure the coercivity while for cell partitions no additional stabilisation is needed. The framework preserves at the interface the discrete conservation properties of the VAG and HFV schemes with fluxes based on local to each cell transmissibility matrices. This discrete conservative form allows to naturally extend the VAG and HFV discretizations of two-phase Darcy flow models to the combined VAG–HFV schemes. The efficiency of our approach is tested for single phase and immiscible two-phase Darcy flows on 3D meshes using a combination of the HFV and VAG discretizations as well as for non-isothermal compositional liquid gas Darcy flows on a vertical 2D cross-section of the Bouillante geothermal reservoir (Guadeloupe) using a combination of the TPFA and VAG discretizations.

•Migraineurs report higher level of multimodal sensory hypersensitivity and higher level of attentional difficulties than control participants.•Sensory hypersensitivity significantly correlates with attentional difficulties in migraineurs, but not with migraine disability or levels of anxiety and depression.•Ictal and interictal sensory sensitivity significantly correlate in migraineurs within visual, auditory and olfactory modalities.

A model coupling a three dimensional gas liquid compositional Darcy flow and a one dimensional compositional free gas flow is presented. The coupling conditions at the interface between the gallery and the porous medium account for the molar normal fluxes continuity for each component, the gas liquid thermodynamical equilibrium, the gas pressure continuity and the gas and liquid molar fractions continuity. This model is applied to the simulation of the mass exchanges at the interface between the repository and the ventilation excavated gallery in a nuclear waste geological repository. The spatial discretization is essentially nodal and based on the vertex approximate gradient (VAG) scheme. Compared with classical nodal approaches such as the Control Volume Finite Element method, the VAG scheme has the advantage to avoid the mixture of different material properties and models in the control volumes located at the interfaces. The discrete model is validated using a quasi analytical solution for the stationary state, and the convergence of the VAG discretization is analysed for a simplified model coupling the Richards approximation in the porous medium and the gas pressure equation in the gallery.

In this article, we introduce a new coupling algorithm between the reservoir multiphase Darcy flow simulator and the geomechanical code accounting for the compaction of the porous medium. The coupling is defined on time periods in such a way that the reservoir unknowns are computed for time steps which are small enough subdivisions of the time period whereas the mechanical problem is solved at the end of the period. Our new approach is based on a nonlinear preconditioned conjugate gradient method which is applied to the mechanical displacement variable. This algorithm is compared, on a one dimensional example, to the staggered coupling algorithm with a porous medium compressibility as relaxation parameter. The main conclusion is that the preconditioned conjugate gradient method is much more robust and converge much faster than the staggered algorithm, while the additional cost per iteration should remain in practical situations very small.

This paper presents a finite volume discretization of two-phase Darcy flows in discrete fracture networks taking into account the mass exchange between the matrix and the fracture. We consider the asymptotic model for which the fractures are represented as interfaces of codimension one immersed in the matrix domain, leading to the so called hybrid dimensional Darcy flow model. The pressures at the interfaces between the matrix and the fracture network are continuous corresponding to a ratio between the normal permeability of the fracture and the width of the fracture assumed to be large compared with the ratio between the permeability of the matrix and the size of the domain. The discretization is an extension of the Vertex Approximate Gradient (VAG) scheme to the case of hybrid dimensional Darcy flow models. Compared with Control Volume Finite Element (CVFE) approaches, the VAG scheme has the advantage to avoid the mixing of the fracture and matrix rocktypes at the interfaces between the matrix and the fractures, while keeping the low cost of a nodal discretization on unstructured meshes. The convergence of the scheme is proved under the assumption that the relative permeabilities are bounded from below by a strictly positive constant. This assumption is needed in the convergence proof in order to take into account discontinuous capillary pressures in particular at the matrix fracture interfaces. The efficiency of our approach compared with CVFE discretizations is shown on two numerical examples of fracture networks in 2D and 3D.

Ziel der Arbeit ist es, Unterschiede in Zusammensetzung und Schweregrad pädiatrischer Notfälle zwischen Luftrettung und bodengebundenem Rettungsdienst darzustellen und ihre Auswirkung auf Aus- und Weiterbildung der Notärzte zu diskutieren.In einer retrospektiven Untersuchung über 3 Jahre (2001–2003) werden 9274 durch Luftrettungsmittel der ADAC-Luftrettung versorgte Kindernotfälle mit 4344 Kindernotfällen, die durch bodengebundene arztbesetzte Rettungsmittel im Saarland versorgt wurden, verglichen.Im Luftrettungsdienst sind Kindernotfälle im Vergleich zum bodengebundenen Notarztdienst häufiger (12,9% vs. 6,4%), traumatologische Notfallbilder überwiegen (59,9% vs. 35,6%) und der Anteil schwerer Verletzungen/Erkrankungen ist größer (30,5% vs. 15,0%). Unabhängig vom Rettungsmittel konzentrieren sich Kindernotfälle auf wenige Notfallbilder: In der Altersgruppe der Kleinkinder ist mehr als jeder dritte Notfall ein Krampfanfall. Es folgen Atemwegserkrankungen und Intoxikationen — deutlich häufiger im bodengebundenen Rettungsdienst. Führendes Verletzungsmuster bei pädiatrischen Traumen ist das Schädel-Hirn-Trauma (SHT), gefolgt von Extremitäten- und Torsoverletzungen. Schwere Verletzungen aller Körperregionen sind häufiger bei Patienten der Luftrettung zu finden.Die Aus- und Weiterbildung der Notärzte sollte neben dem „pediatric life support“ (PLS) eine gezielte Wissensvermittlung zu wenigen spezifischen pädiatrischen Krankheitsbildern umfassen. Für die in der Luftrettung eingesetzten Notärzte ist darüber hinaus ein intensives Training in der pädiatrischen Traumaversorgung notwendig.The aim of this study was to demonstrate differences in structure and severity of pediatric emergencies treated by aeromedical (air rescue) or ground ambulances services. Conclusions for the training of emergency physicians are discussed.In a 3-year study period, a total of 9,274 pediatric emergencies covered by the ADAC air rescue service are compared to 4,344 pediatric patients of ground ambulance services in Saarland.In aeromedical services pediatric emergencies are more frequent (12.9% vs. 6.4%), trauma predominates (59.9% vs. 35.6%) and severe injuries or diseases occur more frequently (30.5% vs. 15.0%). In both groups pediatric emergency cases are concentrated into very few diagnostic groups: more than one third of the cases involving pre-school children is due to convulsions. Respiratory diseases and intoxication are the next most frequent causes and are more common in ground ambulance patients. Head trauma is the most common diagnosis in cases of pediatric trauma, followed by musculoskeletal and thoracoabdominal trauma. All types of severe trauma are more frequent in pediatric patients of the aeromedical services.Training of emergency physicians should include pediatric life support and specific information about frequent pediatric emergency situations. For emergency physicians in aeromedical services, an intensive training in pediatric trauma life support is also necessary.

The simulation of sedimentary basins aims at reconstructing its historical evolution in order to provide quantitative predictions about phenomena leading to hydrocarbon accumulations. The kernel of this simulation is the numerical solution of a complex system of partial differential equations of mixed parabolic–hyperbolic type. A discretisation and linearisation of this system leads to large ill-conditioned nonsymmetric linear systems with three unknowns per mesh element. The preconditioning which we will present for these systems consists in three stages: (i) a local decoupling of the equations which (in addition) aims at concentrating the elliptic part of the system in the “pressure block”; (ii) an efficient preconditioning of the pressure block using AMG; (iii) the “recoupling” of the equations. In all our numerical tests on real case studies we observed a reduction of the CPU-time for the linear solver (up to a factor 4.3 with respect to the current preconditioner ILU(0)) and almost no degradation with respect to physical and numerical parameters.

AbstractIn this paper, we consider a dead-oil model where the capillary pressure is neglected. In a multidimensional space and for a phase-by-phase upstream weigthing cell-centered finite volume scheme, we prove the pressure estimates, the existence of solutions to the discrete equations and the stability of the saturation calculation. This is done in the explicit case as well as in the implicit case. Some numerical tests show the convergence of the scheme.

: Summary. Wavelet methods allow to combine high order accuracy, multilevel preconditioning techniques and adaptive approximation, in order to solve efficiently elliptic operator equations. One of the main difficulty in this context is the efficient treatment of non-homogeneous boundary conditions. In this paper, we propose a strategy that allows to append such conditions in the setting of space refinement (i.e. adaptive) discretizations of second order problems. Our method is based on the use of compatible multiscale decompositions for both the domain and its boundary, and on the possibility of characterizing various function spaces from the numerical properties of these decompositions. In particular, this allows the construction of a lifting operator which is stable for a certain range of smoothness classes, and preserves the compression of the solution in the wavelet basis. An explicit construction of the wavelet bases and the lifting is proposed on fairly general domains, based on conforming domain decomposition techniques.

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Background & Aims: Trefoil factors (TFFs) are secreted gastrointestinal proteins that have been shown to protect and promote healing of the gastrointestinal tract. Moreover, pS2/TFF1 is essential for normal differentiation of the gastric mucosa because deficient mice develop antropyloric adenomas. To date, it is unclear how TFFs mediate their functions. Methods: Using the yeast 2-hybrid system, we attempted to identify murine TFF1 interacting proteins by screening a stomach and duodenum complementary DNA (cDNA) expression library. Results: Four positive clones were isolated. Sequence and expression studies showed that they corresponded to the murine counterpart of human cDNA sequences encoding carboxy-terminal fragments of mMuc2 (489 residues) and mMuc5AC (427, 430, and 894 residues) mucin proteins. Mutagenesis experiments showed that TFF1 interacts with the 2 mucins through binding with their VWFC1 and VWFC2 (von Willebrand factor C) cysteine-rich domains. Conclusions: These results show that the gastrointestinal protective effect of TFF1, and presumably of the other TFFs, is caused at least partially by their participation, via mucin binding, in the correct organization of the mucous layer that protects the apical side of the mucosa from deleterious luminal agents. GASTROENTEROLOGY 2000;118:70-80

This paper aims at proving that, contrary to previous contributions to the subject, Hillsconception of the nonlinear self-consistent scheme, which has been applied in the past toelastoplasticity and to viscoplasticity, can still be adopted with success for elastoviscoplasticity.After a qualitative presentation of the main arguments for this statement, a new Hill-typeapproach is proposed for rate-dependent elastoplastic heterogeneous materials. The associatedlinearization procedure relies on an affine formulation instead of Hills incremental one and onthe use of the correspondence principle to solve the concentration problem; this problem isproved to reduce to a linear viscoelastic one with eigenstrain, i.e. to a linear thermoviscoelasticproblem. The full set of equations is reported for the case of the self-consistent scheme andillustrative applications are given for polycrystals: they are shown to be, as expected, alwayssofter than Kröner-type predictions and to take better into account the viscoelastic coupling andthe associated long range memory effect. In conclusion, the connection and differences betweenthe present approach and other ones already proposed for viscoplastic materials is emphasizedand the limits of Hills conception itself are acknowledged and discussed.

Background:SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1gene. While SMN1produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2to increase SMN protein levels. Methods:FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results:In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions:In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.