Comment lutter contre la fragmentation du système bancaire de la zone euro

Le système bancaire de la zone euro a été fortement touché par deux crises : celle des subprime puis celle des dettes souveraines. Il s'en est suivi un processus de fragmentation du système bancaire qui s'est traduit par des difficultés de financement pour les banques des pays en crise et par une hétérogénéité des conditions de financement – taux des prêts aux ménages et aux entreprises de la zone euro. Si la BCE est parvenue à éviter une crise systémique majeure, cette situation a perturbé la transmission de la politique monétaire au sein de la zone euro. Les mesures mises en oeuvre par la BCE au cours de la crise visent donc à la fois à contrer les risques déflationnistes mais également à restaurer les canaux de transmission de la politique monétaire dans les pays en crise. Bien que la menace déflationniste soit encore prégnante, il semble que les politiques non-conventionnelles ont eu les effets indirects escomptés sur l'efficacité de l'instrument conventionnel de la politique monétaire. Il reste qu'à plus long terme, des mécanismes doivent être envisagés pour renforcer l'intégration financière et rompre le lien entre crise de dette souveraine et crise bancaire. C'est précisément l'objet de l'Union bancaire européenne qui attribue à la BCE de nouveaux pouvoirs en matière de supervision bancaire. Si beaucoup d'experts s'accordent à dire que l'Union bancaire est une grande avancée dans l'approfondissement de l'Europe, il n'en demeure pas moins que plusieurs zones d'ombre subsistent. Les progrès ainsi accomplis ne doivent pas faire oublier que la stabilité bancaire et financière n'est pas complètement assurée et qu'elle ne le sera pas tant que la fragmentation bancaire subsistera entre les pays du coeur et ceux de la périphérie de la zone euro

Matter Power Spectrum Covariance Matrix from the DEUS-PUR {\Lambda}CDM simulations: Mass Resolution and non-Gaussian Errors

The upcoming generation of galaxy surveys will probe the distribution of matter in the universe with unprecedented accuracy. Measurements of the matter power spectrum at different scales and redshifts will provide stringent constraints on the cosmological parameters. However, on non-linear scales this will require an accurate evaluation of the covariance matrix. Here, we compute the covariance matrix of the 3D matter density power spectrum for the concordance $\Lambda$CDM cosmology from an ensemble of N-body simulations of the Dark Energy Universe Simulation - Parallel Universe Runs (DEUS-PUR). This consists of 12288 realisations of a $(656\,h^{-1}\,\textrm{Mpc})^3$ simulation box with $256^3$ particles. We combine this set with an auxiliary sample of 96 simulations of the same volume with $1024^3$ particles. We find N-body mass resolution effect to be an important source of systematic errors on the covariance at high redshift and small intermediate scales. We correct for this effect by introducing an empirical statistical method which provide an accurate determination of the covariance matrix over a wide range of scales including the Baryon Oscillations interval. Contrary to previous studies that used smaller N-body ensembles, we find the power spectrum distribution to significantly deviate from expectations of a Gaussian random density field at $k\gtrsim 0.25\,h\,\textrm{Mpc}^{-1}$ and $z<0.5$. This suggests that in the case of finite volume surveys an unbiased estimate of the ensemble averaged band power at these scales and redshifts may require a careful assessment of non-Gaussian errors more than previously considered.Comment: 9 pages, 8 figures, accepted for publication in MNRAS, covariance matrices available upon request to the author

Politiques monétaires : est-ce le début de la fin ?

Depuis 2009, les principales banques centrales mettent en oeuvre des politiques monétaires expansionnistes afin de stimuler l'activité économique, réduire les risques de spirale déflationniste et soutenir le système financier. Ces politiques se sont traduites par des taux d'intérêt fixés à leur plus bas niveau ou presque et par des mesures non conventionnelles. L'amélioration récente du climat conjoncturel et la volonté affichée des banques centrales d'organiser le retrait progressif des mesures non conventionnelles posent la question d'une éventuelle normalisation des politiques monétaires. Pour autant, toute hausse des taux d'intérêt d'ici 2014 est exclue. En effet, le risque inflationniste est inexistant et la croissance anticipée trop modérée pour entraîner une baisse rapide du taux de chômage. Or, la Réserve fédérale et la Banque d'Angleterre ont conditionné un relèvement du taux d'intérêt à une cible de taux de chômage. Cette politique de communication (forward guidance ou orientation prospective) relative aux taux d'intérêt a pour objectif d'ancrer les anticipations de taux et de fournir par ce biais un soutien à la croissance. Cette stratégie accompagne l'ensemble des mesures non conventionnelles de nature plus quantitatives telles que les programmes d'achat de titre ou les opérations exceptionnelles de refinancement du système bancaire. La normalisation des opérations de politique monétaire passe par un retrait progressif de ces mesures non conventionnelles. Mais l'annonce de Ben Bernanke d'un éventuel ralentissement progressif du rythme des achats de titres par la Réserve fédérale a provoqué de la volatilité sur les marchés et une augmentation rapide des taux à long terme. Dès lors, les banques centrales doivent faire preuve d'une grande prudence afin d'éviter une normalisation trop hâtive des politiques monétaires. Ceci d'autant plus que les risques associés à ces mesures (développement de nouvelles bulles, indépendance des banques centrales ou risques inflationnistes) ne paraissent pas être aujourd'hui la principale menace dans les pays industrialisés

A PNPLA8 frameshift variant in Australian shepherd dogs with hereditary ataxia

Hereditary ataxias are common among canine breeds with various molecular etiology. We identified a hereditary ataxia in young‐adult Australian Shepherd dogs characterized by uncoordinated movements and spasticity, worsening progressively and leading to inability to walk. Pedigree analysis suggested an autosomal recessive transmission. By whole genome sequencing and variant filtering of an affected dog we identified a PNPLA8:c.1169_1170dupTT variant. This variant, located in PNPLA8 (Patatin Like Phospholipase Domain Containing 8), was predicted to induce a PNPLA8:p.(His391PhefsTer394) frameshift, leading to a premature stop codon in the protein. The truncated protein was predicted to lack the functional patatin catalytic domain of PNPLA8, a calcium‐independent phospholipase. PNPLA8 is known to be essential for maintaining mitochondrial energy production through tailoring mitochondrial membrane lipid metabolism and composition. The Australian Shepherd ataxia shares molecular and clinical features with Weaver syndrome in cattle and the mitochondrial‐related neurodegeneration associated with PNPLA8 loss‐of‐function variants in humans. By genotyping a cohort of 85 control Australian Shepherd dogs sampled in France, we found a 4.7% carrier frequency. The PNPLA8:c.[1169_1170dupTT] allele is easily detectable with a genetic test to avoid at‐risk matings

Clinical findings and outcome in feline tetanus: a multicentric retrospective study of 27 cases and review of the literature.

Tetanus is a toxigenic illness caused by the action of Clostridium tetani neurotoxin (TeNT), which results in partial or generalized muscle stiffness in infected mammals and birds. The disease is rarely reported in cats due to their innate resistance to the toxin. This multicentric retrospective study aimed to describe a significant population of cats with a diagnosis of tetanus and report their signalment, clinical and neurological signs, diagnostic findings, treatment, and outcome. A retrospective search through medical records from 11 referral centers in Europe resulted in the identification of 27 cases of feline tetanus from July 2005 to April 2023. These cases were further compared with previously reported cases in the veterinary literature. Young cats were more commonly represented than older cats, with a median age of 4 years. Clinical signs were initially characterized by a lame and/or stiff limb, near the primary injury site, in 17/26 (65%) cats. Signs were focal or multifocal in 21/27 (78%) cats of this study and one typical sign was the inability to flex the most severely affected limbs. Electrodiagnostic studies revealed characteristic changes, such as continuous spontaneous motor unit discharges in both agonist and antagonist muscles. Such studies are particularly useful in focal and multifocal cases and should be performed to further support the diagnosis. The toxin was successfully identified in one case using the mouse bioassay. Treatment included antibiotherapy (metronidazole) in most cases, muscle relaxants, appropriate nursing cares and handling of potential complications. Overall, the outcome appeared to be positive, with only 1/27 (3.7%) cats being euthanized due to financial restrains. 23/25 (92%) cats returned to an independent ambulatory capacity on all limbs within a median delay of 25 days. Mild to moderate long-term sequelae were reported in eight (30%) cats. This multicentric study is the first to bring together such a large number of cats affected with tetanus. Presentation of the disease in cats differs from that observed in humans and dogs, with most cats being locally affected. Compared to previous reports of tetanus, this series of cats had a better outcome overall, especially for cats affected with generalized tetanus

A Phase 1b Study of Telisotuzumab Vedotin in Combination With Nivolumab in Patients With NSCLC

Introduction: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated. Methods: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity. Results: As of January 2020, a total of 37 patients received treatment with Teliso-V (safety population) in combination with nivolumab; 27 patients (efficacy population) were c-Met immunohistochemistry-positive. Programmed death-ligand 1 (PD-L1) status was evaluated in the efficacy population (PD-L1-positive [PD-L1+]: n = 15; PD-L1-negative [PD-L1-]: n = 9; PD-L1-unknown: n = 3). The median age was 67 years and 74% (20 of 27) of patients were naive to immune checkpoint inhibitors. The most common any-grade treatment-related adverse events were fatigue (27%) and peripheral sensory neuropathy (19%). The pharmacokinetic profile of Teliso-V plus nivolumab was similar to Teliso-V monotherapy. The objective response rate was 7.4%, with two patients (PD-L1+, c-Met immunohistochemistry H-score 190, n = 1; PD-L1-, c-Met H-score 290, n = 1) having a confirmed partial response. Overall median progression-free survival was 7.2 months (PD-L1+: 7.2 mo; PD-L1-: 4.5 mo; PD-L1-unknown: not reached). Conclusions: Combination therapy with Teliso-V plus nivolumab was well tolerated in patients with c-Met+ NSCLC with limited antitumor activity

Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa

BACKGROUND: Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI). We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa. METHODS: We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosa monomicrobial nBSI. RESULTS: The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiologic Score (SAPS II), were calculated daily from 2 days prior through 2 days after the first positive blood culture. Calculation of the area under the receiver operating characteristic (ROC) curve confirmed that APACHE II and SAPS II at day -1 and SOFA at day +1 were better predictors of outcome than days -2, 0 and day 2 of BSI. By stepwise logistic regression analysis of these three scoring systems, SAPS II (OR: 13.03, CI95% 2.51–70.49) and APACHE II (OR: 12.51, CI95% 3.12–50.09) on day -1 were the best predictors for mortality. CONCLUSION: SAPS II and APACHE II are more accurate than the SOFA score for predicting mortality in this group of patients at day -1 of BSI

Alix is required for activity-dependent bulk endocytosis at brain synapses

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activitydependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrinindependent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons, we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ADBE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix leads to abnormal synaptic recovery during physiological or pathological repeated stimulations

The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope glycoproteins are both important to regulate a common Env intracellular trafficking

BACKGROUND: Retrovirus particles emerge from the assembly of two structural protein components, Gag that is translated as a soluble protein in the cytoplasm of the host cells, and Env, a type I transmembrane protein. Because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking. RESULTS: We used a CD25 (Tac) chimera-based approach to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey virus Env proteins. We found that the cytoplasmic tails (CTs) of both Env conserved two major signals that control a complex intracellular trafficking. A dileucine-based motif controls the sorting of the chimeras from the trans-Golgi network (TGN) toward endosomal compartments. Env proteins then follow a retrograde transport to the TGN due to the action of a tyrosine-based motif. Mutation of either motif induces the mis-localization of the chimeric proteins and both motifs are found to mediate interactions of the viral CTs with clathrin adaptors. CONCLUSION: This data reveals the unexpected complexity of the intracellular trafficking of retrovirus Env proteins that cycle between the TGN and endosomes. Given that Gag proteins hijack endosomal host proteins, our work suggests that the endosomal pathway may be used by retroviruses to ensure proper encountering of viral structural Gag and Env proteins in cells, an essential step of virus assembly

Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links

BACKGROUND: Evidence for an increased prevalence of candidaemia and for high associated mortality in the 1990s led to a number of different recommendations concerning the management of at risk patients as well as an increase in the availability and prescription of new antifungal agents. The aim of this study was to parallel in our hospital candidemia incidence with the nature of prescribed antifungal drugs between 1993 and 2003. METHODS: During this 10-year period we reviewed all cases of candidemia, and collected all the data about annual consumption of prescribed antifungal drugs RESULTS: Our centralised clinical mycology laboratory isolates and identifies all yeasts grown from blood cultures obtained from a 3300 bed teaching hospital. Between 1993 and 2003, 430 blood yeast isolates were identified. Examination of the trends in isolation revealed a clear decrease in number of yeast isolates recovered between 1995–2000, whereas the number of positive blood cultures in 2003 rose to 1993 levels. The relative prevalence of Candida albicans and C. glabrata was similar in 1993 and 2003 in contrast to the period 1995–2000 where an increased prevalence of C. glabrata was observed. When these quantitative and qualitative data were compared to the amount and type of antifungal agents prescribed during the same period (annual mean defined daily dose: 2662741; annual mean cost: 615629 €) a single correlation was found between the decrease in number of yeast isolates, the increased prevalence of C. glabrata and the high level of prescription of fluconazole at prophylactic doses between 1995–2000. CONCLUSION: Between 1993 and 2000, the number of cases of candidemia halved, with an increase of C. glabrata prevalence. These findings were probably linked to the use of Fluconazole prophylaxis. Although it is not possible to make any recommendations from this data the information is nevertheless interesting and may have considerable implications with the introduction of new antifungal drugs