Piecewise linear transformation in diffusive flux discretization

To ensure the discrete maximum principle or solution positivity in finite volume schemes, diffusive flux is sometimes discretized as a conical combination of finite differences. Such a combination may be impossible to construct along material discontinuities using only cell concentration values. This is often resolved by introducing auxiliary node, edge, or face concentration values that are explicitly interpolated from the surrounding cell concentrations. We propose to discretize the diffusive flux after applying a local piecewise linear coordinate transformation that effectively removes the discontinuities. The resulting scheme does not need any auxiliary concentrations and is therefore remarkably simpler, while being second-order accurate under the assumption that the structure of the domain is locally layered.Comment: 11 pages, 1 figures, preprint submitted to Journal of Computational Physic

Solution and Asymptotic Behavior for a Nonlocal Coupled System of Reaction-Diffusion

This paper concerns with existence, uniqueness and asymptotic behavior of the solutions for a nonlocal coupled system of reaction-diffusion. We prove the existence and uniqueness of weak solutions by the Faedo-Galerkin method and exponential decay of solutions by the classic energy method. We improve the results obtained by Chipot-Lovato and Menezes for coupled systems. A numerical scheme is presented

Coupling techniques for nonlinear hyperbolic equations. III. The well-balanced approximation of thick interfaces

We continue our analysis of the coupling between nonlinear hyperbolic problems across possibly resonant interfaces. In the first two parts of this series, we introduced a new framework for coupling problems which is based on the so-called thin interface model and uses an augmented formulation and an additional unknown for the interface location; this framework has the advantage of avoiding any explicit modeling of the interface structure. In the present paper, we pursue our investigation of the augmented formulation and we introduce a new coupling framework which is now based on the so-called thick interface model. For scalar nonlinear hyperbolic equations in one space variable, we observe that the Cauchy problem is well-posed. Then, our main achievement in the present paper is the design of a new well-balanced finite volume scheme which is adapted to the thick interface model, together with a proof of its convergence toward the unique entropy solution (for a broad class of nonlinear hyperbolic equations). Due to the presence of a possibly resonant interface, the standard technique based on a total variation estimate does not apply, and DiPerna's uniqueness theorem must be used. Following a method proposed by Coquel and LeFloch, our proof relies on discrete entropy inequalities for the coupling problem and an estimate of the discrete entropy dissipation in the proposed scheme.Comment: 21 page

How much larger quantum correlations are than classical ones

Considering as distance between two two-party correlations the minimum number of half local results one party must toggle in order to turn one correlation into the other, we show that the volume of the set of physically obtainable correlations in the Einstein-Podolsky-Rosen-Bell scenario is (3 pi/8)^2 = 1.388 larger than the volume of the set of correlations obtainable in local deterministic or probabilistic hidden-variable theories, but is only 3 pi^2/32 = 0.925 of the volume allowed by arbitrary causal (i.e., no-signaling) theories.Comment: REVTeX4, 6 page

Probabilistic analysis of the upwind scheme for transport

We provide a probabilistic analysis of the upwind scheme for multi-dimensional transport equations. We associate a Markov chain with the numerical scheme and then obtain a backward representation formula of Kolmogorov type for the numerical solution. We then understand that the error induced by the scheme is governed by the fluctuations of the Markov chain around the characteristics of the flow. We show, in various situations, that the fluctuations are of diffusive type. As a by-product, we prove that the scheme is of order 1/2 for an initial datum in BV and of order 1/2-a, for all a>0, for a Lipschitz continuous initial datum. Our analysis provides a new interpretation of the numerical diffusion phenomenon

High-resolution Antibody Profiling of KSHV-infectedIndividuals Presenting With and Without Kaposi Sarcoma Reveals Distinct Viral-Exposure Signatures

Kaposi sarcoma-associated herpesvirus (KSHV) is a gamma herpesvirus and the etiologic agent of Kaposi sarcoma (KS), an AIDS-defining cancer affecting immunocompromised individuals. Sub-Saharan Africa (SSA) exhibits a particularly high KSHV prevalence. Immune suppression in addition to KSHV infection is thought to drive KS development. However, cofactors such as prior infections may influence pathogenesis or lack thereof. Elucidation of humoral antibody (Ab) repertoire is vital to discern host-pathogen interactions, define detection and prognostic biomarkers, and contribute to vaccine development strategies. Here, we utilized VirScan, a high-throughput phage display library containing 56-mer, overlapping peptide tiles, spanning the entire proteomes of all known human pathogens coupled with phage immunoprecipitation sequencing (PhIP-seq). We identified and quantified Ab responses against 556 viral organisms. Serum samples (n=106) derived from Sub-Saharan Africans stratified to three groups: (1) KSHV seronegative (n=25), (2) KSHV seropositive (n=22), and (3) KS (n=59) were analyzed. Each group is further stratified based on their HIV serostatus. To compare the humoral responses between groups, we quantified the Ab responses based on (1) breadth (sum of significantly enriched, or reactive peptides) and (2) magnitude (the frequency of which a reactive peptide is targeted). We explored whether peptide-, protein- and organism-level Ab responses can discriminate between symptomatic disease (KS) and asymptomatic infection (ASY). Overall, comparison of the Ab repertoire indicated that HIV or KSHV infection leads to a less diverse Ab response against viral infections. Specifically, while KSHV infection alone displayed a diminished Ab repertoire relative to uninfected controls, HIV co-infection exhibited diminished repertoire to a greater extent, suggestive of HIV’s immunosuppressive qualities, providing an aggregate effect when co-infected with KSHV. Statistical comparison of organismlevel breadth between KS and ASY subjects revealed ~30 differentially recognized organisms. We detected significantly higher breadth of Ab responses to hepatitis B, C, and E viruses. Conversely, ASY individuals presented higher breadth against enteroviruses. Focusing on the protein- and peptide-level responses, pattern recognition and network analyses highlighted Ab responses co-occurring with previously reported discriminative KSHV peptides. Thorough proteome annotations and sequence analyses identified clusters of immunodominant proteins and epitopes unique to, or cross-reactive with other viruses. In conclusion, our data elucidated \u3e1,000 peptide-level Ab responses from \u3e50 potential co-infections that discriminate KS from ASY. To validate these peptides and their predictive, prognostic, and therapeutic value, we will analyze these peptides in larger cohorts and longitudinally

A Very High-Order Accurate Staggered Finite Volume Scheme for the Stationary Incompressible Navier–Stokes and Euler Equations on Unstructured Meshes

International audienceWe propose a sixth-order staggered finite volume scheme based on polynomial reconstructions to achieve high accurate numerical solutions for the incompressible Navier-Stokes and Euler equations. The scheme is equipped with a fixed-point algorithm with solution relaxation to speed-up the convergence and reduce the computation time. Numerical tests are provided to assess the effectiveness of the method to achieve up to sixth-order con-2 Ricardo Costa et al. vergence rates. Simulations for the benchmark lid-driven cavity problem are also provided to highlight the benefit of the proposed high-order scheme

Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study

Abiraterona; Cabazitaxel; Factor pronósticoAbiraterona; Cabazitaxel; Factor pronòsticAbiraterone; Cabazitaxel; Prognostic factorBackground There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker. Patients and methods CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan–Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS. Results The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608). Conclusions High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.This work was supported by Sanofi Genzyme (no grant number). The authors were responsible for all content and editorial decisions and received no honoraria for development of this manuscript

Consensus-based care recommendations for adults with myotonic dystrophy type 1

Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. Summary The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments. Described as “one of the more variable diseases found in medicine,” myotonic dystrophy type 1 (DM1) is an autosomal dominant, triplet-repeat expansion disorder that affects somewhere between 1:3,000 and 1:8,000 individuals worldwide.1 There is a modest association between increased repeat expansion and disease severity, as evidenced by the average age of onset and overall morbidity of the condition. An expansion of over 35 repeats typically indicates an unstable and expanding mutation. An expansion of 50 repeats or higher is consistent with a diagnosis of DM1. DM1 is a multisystem and heterogeneous disease characterized by distal weakness, atrophy, and myotonia, as well as symptoms in the heart, brain, gastrointestinal tract, endocrine, and respiratory systems. Symptoms may occur at any age. The severity of the condition varies widely among affected individuals, even among members of the same family. Comprehensive evidence-based guidelines do not currently exist to guide the treatment of DM1 patients. As a result, the international patient community reports varied levels of care and care quality, and difficulty accessing care adequate to manage their symptoms, unless they have access to multidisciplinary neuromuscular clinics. Consensus-based care recommendations can help standardize and improve the quality of care received by DM1 patients and assist clinicians who may not be familiar with the significant variability, range of symptoms, and severity of the disease. Care recommendations can also improve the landscape for clinical trial success by eliminating some of the inconsistencies in patient care to allow more accurate understanding of the benefit of potential therapies

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder