128 research outputs found
MPFR: A Multiple-Precision Binary Floating-Point Library With Correct Rounding
This paper presents a multiple-precision binary floating-point library, written in the ISO C language, and based on the GNU MP library. Its particularity is to extend ideas from the IEEE-754 standard to arbitrary precision, by providing correct rounding and exceptions. We demonstrate how these strong semantics are achieved | with no signicant slowdown with respect to other tools | and discuss a few applications where such a library can be useful
Identifying uncertainties in scenarios and models of socio-ecological systems in support of decision-making
There are many sources of uncertainty in scenarios and models of socio-ecological systems, and understanding these uncertainties is critical in supporting informed decision-making about the management of natural resources. Here, we review uncertainty across the steps needed to create socio-ecological scenarios, from narrative storylines to the representation of human and biological processes in models and the estimation of scenario and model parameters. We find that socio-ecological scenarios and models would benefit from moving away from “stylized” approaches that do not consider a wide range of direct drivers and their dependency on indirect drivers. Indeed, a greater focus on the social phenomena is fundamental in understanding the functioning of nature on a human-dominated planet. There is no panacea for dealing with uncertainty, but several approaches to evaluating uncertainty are still not routinely applied in scenario modeling, and this is becoming increasingly unacceptable. However, it is important to avoid uncertainties becoming an excuse for inaction in decision-making when facing environmental challenges.</p
Comprendre la mondialisation II
Après l'économie, nous continuons à explorer les multiples composants de la mondialisation. Des analystes politiques nous éclairent sur les mutations en cours : le rôle des États face à l'émancipation des forces économiques, le jeu des organisations supranationales, l'avenir de la démocratie à l'ère du global, les formes d'appropriation ou de rejet de la mondialisation par les citoyens... Citoyens du monde, mondialité... L'explosion des nouvelles technologies de l'information et de la communi..
The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective
Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30–80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an “off-label” prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD
A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing
Purpose
Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned.
Methods
Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted.
Results
We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency).
Conclusion
The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock
Dupire (M.) et Boutillier (J.-L.). Le pays adioukrou et sa palmeraie, étude socio-économique (L'Homme d'Outre-Mer, fasc. 4, 1958)
Pélissier Paul. Dupire (M.) et Boutillier (J.-L.). Le pays adioukrou et sa palmeraie, étude socio-économique (L'Homme d'Outre-Mer, fasc. 4, 1958). In: Cahiers d'outre-mer. N° 44 - 11e année, Octobre-décembre 1958. pp. 436-437
Les Diola : étude sur l'habitat des riziculteurs de Basse-Casamance
Pélissier Paul. Les Diola : étude sur l'habitat des riziculteurs de Basse-Casamance. In: Cahiers d'outre-mer. N° 44 - 11e année, Octobre-décembre 1958. pp. 334-388
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