La règle monétaire de McCallum revue à la lumière de la méthodologie de Litterman

Depuis l’abandon du contrôle des agrégats monétaires par les grandes banques centrales, la règle de McCallum a attiré une attention soutenue dans la littérature macroéconomique. Tant McCallum que ses critiques ont tenté de cerner le caractère stabilisateur de la règle et sa robustesse sous différents régimes et modèles. Dans cet article, nous adoptons une vision pragmatique et tentons de mettre en lumière des facettes empiriques méconnues de la règle de McCallum en utilisant une méthodologie qui allie judicieusement l’utilisation d’un modèle BVAR de l’économie américaine et la théorie du contrôle optimal (Litterman, 1987). Nos résultats montrent i. que la base monétaire est un instrument relativement anémique de la politique monétaire américaine; ii. que son utilisation pour stabiliser le revenu nominal peut mener à des fluctuations difficilement acceptables de l’ensemble des autres variables du système et est donc sujette à la critique de Lucas; iii. qu’il est possible, à l’aide du contrôle optimal, de pousser l’analyse de la règle et de trouver de nouvelles configurations qui ont de meilleures propriétés stabilisatrices des variables objectifs.Since the abandonment of monetary targeting by the Central Banks of major industrial nations, McCallum's rule has attracted renewed attention in the macroeconomic literature. Both McCallum and his critics have investigated the stabilizing properties of the rule and its robustness across regimes and models. In this paper, we adopt the same pragmatic view and seek to discover some unknown empirical properties of McCallum's rule by using a methodology that blends a BVAR model of the U.S. economy to the theory of optimal control (Litterman, 1987). Our results indicate that i. the monetary base is a rather weak instrument of U.S. monetary policy; ii. its use to stabilize nominal income leads to large fluctuations in the other variables of the system subjecting the whole exercise to the Lucas critique; iii. that optimal control analysis can be used to investigate marginally different configurations of McCallum's rule that have better overall stabilizing properties

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

Genome-Wide Association Study and Functional Characterization Identifies Candidate Genes for Insulin-Stimulated Glucose Uptake

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in \u3e55,000 participants from three ancestry groups. We identified ten new loci (P \u3c 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Evaluation of the Statistical Properties of Minimal Sufficient Balance as a Method for Controlling Baseline Covariate Imbalance for Sequential Clinical Trials with a Binary Endpoint

When there is a large number of baseline covariates whose imbalance needs to be controlled in sequential randomized controlled trials, minimization is most commonly used for randomizing treatment assignments. The lack of allocation randomness associated with the minimization method has been the source of controversy. The minimal sufficient balance (MSB) method is an alternative to minimization. It prevents serious imbalance from a large number of covariates while maintaining high levels of allocation randomness. However, a formal comparison between covariate-adaptive methods of randomization has not yet been studied. Using a re-randomization of the rt-PA clinical trial dataset with 1:1 equal allocation, minimization and MSB methods are compared with respect to allocation randomness, effectiveness at balancing covariates across treatment arms, and preservation of the nominal type I error rate. Using a simulated dataset, power and bias in the estimation of treatment effect are studied for completely randomized design, stratified permuted blocks, minimization, and MSB. A novel randomization method, known as allocation ratio preserving Minimal Sufficient Balance (ARP MSB) is presented as an alternative to allocation ratio preserving biased coin minimization (ARP BCM). Using a re-randomization of the rt-PA clinical trial dataset, ARP BCM and ARP MSB are compared with respect to the allocation randomness, effectiveness at balancing covariates across treatment arms, and preservation of the nominal type I error rate in unequal allocation clinical trials. MSB and ARP MSB methods proved to have equal or superior effectiveness at controlling imbalance on a combination of continuous and categorical variables, as well as a far greater proportion of completely random treatment assignments compared to the minimization and ARP BCM methods. MSB, ARP MSB, minimization, and ARP BCM all proved to have similar properties with respect to type I error rate preservation, power, and bias in measuring treatment effects. MSB and ARP MSB, while not presented as optimal methods for controlling covariate imbalances in sequential clinical trials, provide an alternative to the minimization and ARP BCM methods. The arguments in this dissertation should be considered by those who wish to use minimization or ARP BCM for subject allocation in clinical trials

L’inventaire des lieux de mémoire de la Nouvelle-France au Québec

In 1998, the Ministère de la Culture et des Communications du Québec initiated an inventory of architectural and archaeological heritage from the New France period at the instigation of the Commission franco–québécoise des lieux de mémoire communs. This article describes the conceptual issues that arose in the course of a pilot project aimed at exploring innovative approaches to inventory work, be they related to its scientific bases (broader concept of heritage, relationship between historic sites and historic events), realization (international collaboration between Québec and France) or the dissemination of its results (use of information technology)