A class of Discontinuous Galerkin methods for nonlinear variational problems

In the context of Discontinuous Galerkin methods, we study approximations of nonlinear variational problems associated with convex energies. We propose element-wise nonconforming finite element methods to discretize the continuous minimisation problem. Using $\Gamma$-convergence arguments we show that the discrete minimisers converge to the unique minimiser of the continuous problem as the mesh parameter tends to zero, under the additional contribution of appropriately defined penalty terms at the level of the discrete energies. We finally substantiate the feasibility of our methods by numerical examples

Cells exploit a phase transition to mechanically remodel the fibrous extracellular matrix

Through mechanical forces, biological cells remodel the surrounding collagen network, generating striking deformation patterns. Tethers—tracts of high densification and fibre alignment—form between cells, thinner bands emanate from cell clusters. While tethers facilitate cell migration and communication, how they form is unclear. Combining modelling, simulation and experiment, we show that tether formation is a densification phase transition of the extracellular matrix, caused by buckling instability of network fibres under cell-induced compression, featuring unexpected similarities with martensitic microstructures. Multiscale averaging yields a two-phase, bistable continuum energy landscape for fibrous collagen, with a densified/aligned second phase. Simulations predict strain discontinuities between the undensified and densified phase, which localizes within tethers as experimentally observed. In our experiments, active particles induce similar localized patterns as cells. This shows how cells exploit an instability to mechanically remodel the extracellular matrix simply by contracting, thereby facilitating mechanosensing, invasion and metastasis

Programmed inappropriate ICD ventricular defibrillation for cardioversion of persistent atrial fibrillation

In this report we briefly describe a patient with a dual chamber implantable cardioverter defibrillator in the context of severe ischemic cardiomyopathy who developed persistent atrial fibrillation. After appropriate anticoagulation and under mild sedation the patient was successfully cardioverted to sinus rhythm after a programmed ventricular synchronized defibrillation using his defibrillator. Programmed internal cardioversion of persistent atrial fibrillation in patients who have an implantable cardioverter defibillator without atrial defibrillation capabilities could be an effective and safe therapeutic option. Unlike external electrical cardioversion, this strategy does not interfere with the implantable cardioverter defibrillator, is more effective, and obviates the need of general anesthesia. This strategy should be further evaluated in clinical trials

The Prevalence of Immunologic Injury in Renal Allograft Recipients with De Novo Proteinuria

Post-transplant proteinuria is a common complication after renal transplantation; it is associated with reduced graft and recipient survival. However, the prevalence of histological causes has been reported with considerable variation. A clinico-pathological re-evaluation of post-transplant proteinuria is necessary, especially after dismissal of the term “chronic allograft nephropathy,” which had been considered to be an important cause of proteinuria. Moreover, urinary protein can promote interstitial inflammation in native kidney, whether this occurs in renal allograft remains unknown. Factors that affect the graft outcome in patients with proteinuria also remain unclear. Here we collected 98 cases of renal allograft recipients who developed proteinuria after transplant, histological features were characterized using Banff scoring system. Cox proportional hazard regression models were used for graft survival predictors. We found that transplant glomerulopathy was the leading (40.8%) cause of post-transplant proteinuria. Immunological causes, including transplant glomerulopathy, acute rejection, and chronic rejection accounted for the majority of all pathological causes of proteinuria. Nevertheless, almost all patients that developed proteinuria had immunological lesions in the graft, especially for interstitial inflammation. Intraglomerular C3 deposition was unexpectedly correlated with the severity of proteinuria. Moreover, the severity of interstitial inflammation was an independent risk factor for graft loss, while high level of hemoglobin was a protective factor for graft survival. This study revealed a predominance of immunological parameters in renal allografts with post-transplant proteinuria. These parameters not only correlate with the severity of proteinuria, but also with the outcome of the graft

The role of molecular genetics in diagnosing familial hematuria(s)

Familial microscopic hematuria (MH) of glomerular origin represents a heterogeneous group of monogenic conditions involving several genes, some of which remain unknown. Recent advances have increased our understanding and our ability to use molecular genetics for diagnosing such patients, enabling us to study their clinical characteristics over time. Three collagen IV genes, COL4A3, COL4A4, and COL4A5 explain the autosomal and X-linked forms of Alport syndrome (AS), and a subset of thin basement membrane nephropathy (TBMN). A number of X-linked AS patients follow a milder course reminiscent of that of patients with heterozygous COL4A3/COL4A4 mutations and TBMN, while at the same time a significant subset of patients with TBMN and familial MH progress to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). A mutation in CFHR5, a member of the complement factor H family of genes that regulate complement activation, was recently shown to cause isolated C3 glomerulopathy, presenting with MH in childhood and demonstrating a significant risk for CKD/ESKD after 40 years old. Through these results molecular genetics emerges as a powerful tool for a definite diagnosis when all the above conditions enter the differential diagnosis, while in many at-risk related family members, a molecular diagnosis may obviate the need for another renal biopsy

Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using Next Generation Sequencing (NGS) for five genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, nine of them novel. In five families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, eight (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-yrs, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies

«La relation de limitation et d’exception dans le français d’aujourd’hui : excepté, sauf et hormis comme pivots d’une relation algébrique »

L’analyse des emplois prépositionnels et des emplois conjonctifs d’ “excepté”, de “sauf” et d’ “hormis” permet d’envisager les trois prépositions/conjonctions comme le pivot d’un binôme, comme la plaque tournante d’une structure bipolaire. Placées au milieu du binôme, ces prépositions sont forcées par leur sémantisme originaire dûment métaphorisé de jouer le rôle de marqueurs d’inconséquence systématique entre l’élément se trouvant à leur gauche et celui qui se trouve à leur droite. L’opposition qui surgit entre les deux éléments n’est donc pas une incompatibilité naturelle, intrinsèque, mais extrinsèque, induite. Dans la plupart des cas (emplois limitatifs), cette opposition prend la forme d’un rapport entre une « classe » et le « membre (soustrait) de la classe », ou bien entre un « tout » et une « partie » ; dans d’autres (emplois exceptifs), cette opposition se manifeste au contraire comme une attaque de front portée par un « tout » à un autre « tout ». De plus, l’inconséquence induite mise en place par la préposition/conjonction paraît, en principe, tout à fait insurmontable. Dans l’assertion « les écureuils vivent partout, sauf en Australie » (que l’on peut expliciter par « Les écureuils vivent partout, sauf [qu’ils ne vivent pas] en Australie »), la préposition semble en effet capable d’impliquer le prédicat principal avec signe inverti, et de bâtir sur une telle implication une sorte de sous énoncé qui, à la rigueur, est totalement inconséquent avec celui qui le précède (si « les écureuils ne vivent pas en Australie », le fait qu’ils « vivent partout » est faux). Néanmoins, l’analyse montre qu’alors que certaines de ces oppositions peuvent enfin être dépassées, d’autres ne le peuvent pas. C’est, respectivement, le cas des relations limitatives et des relations exceptives. La relation limitative, impliquant le rapport « tout » - « partie », permet de résoudre le conflit dans les termes d’une somme algébrique entre deux sous énoncés pourvus de différent poids informatif et de signe contraire. Les valeurs numériques des termes de la somme étant déséquilibrées, le résultat est toujours autre que zéro. La relation exceptive, au contraire, qui n’implique pas le rapport « tout » - « partie », n’est pas capable de résoudre le conflit entre deux sous énoncés pourvus du même poids informatif et en même temps de signe contraire : les valeurs numériques des termes de la somme étant symétriques et égales, le résultat sera toujours équivalent à zéro