Une introduction aux subventions intergouvernementales

Notre article vise principalement à donner des notions élémentaires sur les fondements de la théorie des subventions intergouvernementales, qui pourront être utiles aux nouveaux venus dans ce domaine actif de la recherche. En outre, nous donnons un aperçu sélectif des récents articles théoriques sur les subventions, en soulignant particulièrement les jeux non coopératifs entre divers niveaux de gouvernement dans un système fédéral. Les parties de notre article correspondent à des sujets généraux : les subventions de péréquation, les subventions liées au partage des recettes et les subventions conditionnelles. Pour rehausser la valeur pédagogique de cet article, nous fournissons pour chaque sujet une étude mathématique simple et unifiée (dans la mesure du possible) qui accompagnera une description discursive des points principaux relevés dans la documentation.The principal aim of our paper is to provide a primer on the foundations of the theory of intergovernmental grants, suitable for newcomers to this active field of research. In addition, we provide a selective survey of recent theoretical papers on grants, focusing particularly on non-cooperative games between different levels of government in a federal system. The sections of the paper correspond to broad topics: equalization grants, revenue-sharing grants, and conditional grants. To enhance the paper's pedagogical value, we provide a simple and (as much as possible) unifïed mathematical treatment of each topic to accompany a discursive description of the main insights found in the literature

Une introduction aux subventions intergouvernementales

The principal aim of our paper is to provide a primer on the foundations of the theory of intergovernmental grants, suitable for newcomers to this active field of research. In addition, we provide a selective survey of recent theoretical papers on grants, focusing particularly on non-cooperative games between different levels of government in a federal system. The sections of the paper correspond to broad topics: equalization grants, revenue-sharing grants, and conditional grants. To enhance the paper's pedagogical value, we provide a simple and (as much as possible) unifïed mathematical treatment of each topic to accompany a discursive description of the main insights found in the literature. Notre article vise principalement à donner des notions élémentaires sur les fondements de la théorie des subventions intergouvernementales, qui pourront être utiles aux nouveaux venus dans ce domaine actif de la recherche. En outre, nous donnons un aperçu sélectif des récents articles théoriques sur les subventions, en soulignant particulièrement les jeux non coopératifs entre divers niveaux de gouvernement dans un système fédéral. Les parties de notre article correspondent à des sujets généraux : les subventions de péréquation, les subventions liées au partage des recettes et les subventions conditionnelles. Pour rehausser la valeur pédagogique de cet article, nous fournissons pour chaque sujet une étude mathématique simple et unifiée (dans la mesure du possible) qui accompagnera une description discursive des points principaux relevés dans la documentation.

Prion protein gene mutation detection using long-read Nanopore sequencing

Prion diseases are fatal neurodegenerative conditions that affect humans and animals. Rapid and accurate sequencing of the prion gene PRNP is paramount to human prion disease diagnosis and for animal surveillance programmes. Current methods for PRNP genotyping involve sequencing of small fragments within the protein-coding region. The contribution of variants in the non-coding regions of PRNP including large structural changes is poorly understood. Here, we used long-range PCR and Nanopore sequencing to sequence the full length of PRNP, including its regulatory region, in 25 samples from blood and brain of individuals with inherited or sporadic prion diseases. Nanopore sequencing detected the same variants as identified by Sanger sequencing, including repeat expansions/deletions. Nanopore identified additional single-nucleotide variants in the non-coding regions of PRNP, but no novel structural variants were discovered. Finally, we explored somatic mosaicism of PRNP's octapeptide repeat region, which is a hypothetical cause of sporadic prion disease. While we found changes consistent with somatic mutations, we demonstrate that they may have been generated by the PCR. Our study illustrates the accuracy of Nanopore sequencing for rapid and field prion disease diagnosis and highlights the need for single-molecule sequencing methods for the detection of somatic mutations

Des equations de Dirac et de Schrodinger pour la transformation de Fourier

Dyson a associe aux determinants de Fredholm des noyaux de Dirichlet pairs (resp. impairs) une equation de Schrodinger sur un demi-axe et a employe les methodes du scattering inverse de Gel'fand-Levitan et de Marchenko, en tandem, pour etudier l'asymptotique de ces determinants. Nous avons propose suite a notre mise-au-jour de l'operateur conducteur de chercher a realiser la transformation de Fourier elle-meme comme un scattering, et nous obtenons ici dans ce but deux systemes de Dirac sur l'axe reel tout entier et qui sont associes intrinsequement, respectivement, aux transformations en cosinus et en sinus. (Dyson has associated with the Fredholm determinants of the even (resp. odd) Dirichlet kernels a Schrodinger equation on the half-axis and has used, in tandem, the Gel'fand-Levitan and Marchenko methods of inverse scattering theory to study the asymptotics of these determinants. We have proposed following our unearthing of the conductor operator to seek to realize the Fourier transform itself as a scattering, and we obtain here to this end two Dirac systems on the entire real axis which are intrinsically associated, respectively, to the cosine and to the sine transforms.)Comment: 8 pages, with a summary in English. One or two things adde

The TatC component of the twin-arginine protein translocase functions as an obligate oligomer

The Tat protein export system translocates folded proteins across the bacterial cytoplasmic membrane and the plant thylakoid membrane. The Tat system in Escherichia coli is composed of TatA, TatB and TatC proteins. TatB and TatC form an oligomeric, multivalent receptor complex that binds Tat substrates, while multiple protomers of TatA assemble at substrate-bound TatBC receptors to facilitate substrate transport. We have addressed whether oligomerisation of TatC is an absolute requirement for operation of the Tat pathway by screening for dominant negative alleles of tatC that inactivate Tat function in the presence of wild-type tatC. Single substitutions that confer dominant negative TatC activity were localised to the periplasmic cap region. The variant TatC proteins retained the ability to interact with TatB and with a Tat substrate but were unable to support the in vivo assembly of TatA complexes. Blue-native PAGE analysis showed that the variant TatC proteins produced smaller TatBC complexes than the wild-type TatC protein. The substitutions did not alter disulphide crosslinking to neighbouring TatC molecules from positions in the periplasmic cap but abolished a substrate-induced disulphide crosslink in transmembrane helix 5 of TatC. Our findings show that TatC functions as an obligate oligomer.</p

Predictive ability of an early diagnostic guess in patients presenting with chest pain; a longitudinal descriptive study

The intuitive early diagnostic guess could play an important role in reaching a final diagnosis. However, no study to date has attempted to quantify the importance of general practitioners' (GPs) ability to correctly appraise the origin of chest pain within the first minutes of an encounter. The validation study was nested in a multicentre cohort study with a one year follow-up and included 626 successive patients who presented with chest pain and were attended by 58 GPs in Western Switzerland. The early diagnostic guess was assessed prior to a patient's history being taken by a GP and was then compared to a diagnosis of chest pain observed over the next year. Using summary measures clustered at the GP's level, the early diagnostic guess was confirmed by further investigation in 51.0% (CI 95%; 49.4% to 52.5%) of patients presenting with chest pain. The early diagnostic guess was more accurate in patients with a life threatening illness (65.4%; CI 95% 64.5% to 66.3%) and in patients who did not feel anxious (62.9%; CI 95% 62.5% to 63.3%). The predictive abilities of an early diagnostic guess were consistent among GPs. The GPs early diagnostic guess was correct in one out of two patients presenting with chest pain. The probability of a correct guess was higher in patients with a life-threatening illness and in patients not feeling anxious about their pain

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success

Mortalidad de aves marinas producida por luces artificiales terrestres

Artificial lights at night cause high mortality of seabirds, one of the most endangered groups of birds globally. Fledglings of burrow-nesting seabirds, and to a lesser extent adults, are attracted to and then grounded (i.e., forced to land) by lights when they fly at night. We reviewed the current state of knowledge of seabird attraction to light to identify information gaps and propose measures to address the problem. Although species in families such as Alcidae and Anatidae can be grounded by artificial light, the most affected seabirds are petrels and shearwaters (Procellariiformes). At least 56 species of Procellariiformes, more than one-third of them (24) threatened, are subject to grounding by lights. Seabirds grounded by lights have been found worldwide, mainly on oceanic islands but also at some continental locations. Petrel breeding grounds confined to formerly uninhabited islands are particularly at risk from light pollution due to tourism and urban sprawl. Where it is impractical to ban external lights, rescue programs of grounded birds offer the most immediate and employed mitigation to reduce the rate of light-induced mortality and save thousands of birds every year. These programs also provide useful information for seabird management. However, these data are typically fragmentary, biased, and uncertain and can lead to inaccurate impact estimates and poor understanding of the phenomenon of seabird attraction to lights. We believe the most urgently needed actions to mitigate and understand light-induced mortality of seabirds are estimation of mortality and effects on populations; determination of threshold light levels and safe distances from light sources; documentation of the fate of rescued birds; improvement of rescue campaigns, particularly in terms of increasing recovery rates and level of care; and research on seabird-friendly lights to reduce attraction.RESUMEN: Las luces artificiales nocturnas causan una mortalidad alta de aves marinas, uno de los grupos de aves en mayor peligro de extinción a nivel mundial. Los polluelos de aves marinas que anidan en madrigueras, y en menor medida los adultos, son atraídos y forzados a aterrizar por las luces cuando vuelan de noche. Revisamos el estado actual del conocimiento sobre la atracción de las aves marinas por la luz para identificar vacíos de información y proponer medidas para resolver el problema. Aunque las especies de familias como Alcidae y Anatidae pueden ser forzadas a aterrizar por la luz artificial, las aves marinas más afectadas son los petreles y las pardelas (Procellariiformes). Por lo menos 56 especies de Procellariiformes, más de un tercio (24) de ellas amenazadas, son propensas al aterrizaje atraídas por las luces. Las aves marinas forzadas a aterrizar han sido halladas en todo el mundo, principalmente en islas oceánicas, pero también en algunas localidades continentales. Los sitios de anidación de los petreles confinados anteriormente a islas deshabitadas están particularmente en riesgo de sufrir contaminación lumínica debido al turismo y al crecimiento urbano. En donde no es práctico prohibir las luces externas, los programas de rescate de las aves accidentadas ofrecen la mitigación más inmediata y empleada para reducir la tasa de mortalidad inducida por la luz y salvar a miles de aves cada año. Estos programas también proporcionan información útil para el manejo de aves marinas. Sin embargo, estos datos están típicamente fragmentados, sesgados y son inciertos, y pueden llevar a estimaciones inexactas del impacto y a un entendimiento pobre del fenómeno de la atracción de las aves marinas por la luz. Creemos que las acciones necesarias de mayor urgencia para mitigar y entender la mortalidad de aves marinas producida por la luz son: la estimación de la mortalidad y los efectos sobre la población; la determinación de umbrales de niveles de luz y de distancias seguras a las fuentes de luz; el estudio del destino de las aves rescatadas; la mejora de las campañas de rescate, particularmente en términos de incrementar las tasas de recogida y el nivel de cuidado; y la investigación sobre las características de la luz para reducir la atracción de las aves marinas.This research was supported by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme (Project ID: 330655 FP7-PEOPLE-2012-IOF)info:eu-repo/semantics/publishedVersio

Genetic and phenotypic spectrum associated with IFIH1 gain-of-function

IFIH1 gain-of-function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate