Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on metabolic and nutritional aspects. Effects of 3 g/day paracetamol for 14 days on fasting blood glutathione, plasma amino acids and sulfate, urinary paracetamol metabolites, and urinary metabolomic were studied in independently living older persons (five women, five men, mean (+/- SEM) age 74 +/- 1 years). Dietary intakes were recorded before and at the end of the treatment and ingested sulfur amino acids were evaluated. Fasting blood glutathione, plasma amino acids, and sulfate were unchanged. Urinary nitrogen excretion supported a preservation of whole body proteins, but large-scale urinary metabolomic analysis revealed an oxidation of some sulfur-containing compounds. Dietary protein intake was 13% higher at the end than before paracetamol treatment. Final sulfur amino acid intake reached 37 mg/kg/day. The increase in sulfur amino acid intake corresponded to half of the sulfur excreted in urinary paracetamol conjugates. In conclusion, older persons accommodated to long-term paracetamol treatment by increasing dietary protein intake without any mobilization of body proteins, but with decreased anti-oxidative defenses. The extra demand in sulfur amino acids led to a consumption far above the corresponding population-safe recommendation

Diving below the spin-down limit:constraints on gravitational waves from the energetic young pulsar PSR J0537-6910

We present a search for continuous gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537-6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using NICER data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537-6910 has the largest spin-down luminosity of any pulsar and is highly active with regards to glitches. Analyses of its long-term and inter-glitch braking indices provided intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency. We find no signal, however, and report our upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of two and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is limited to less than about 3 x 10⁻⁵, which is the third best constraint for any young pulsar

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

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

Mettre en situation et accompagner la construction de connaissances : un parti pris pour la formation à l’accompagnement de projets en agriculture

This article is about an experiment in agricultural higher education. Faced with change and uncertainty in agriculture, agricultural advisors need to deal with new stakes. For example, the profiles of people who want to set up a farm are changing, which requires to consider new ways of helping them to achieve their goals. How to help students to move towards such changing professions ? We consider that supporting students’ reflexivity is a good way to help them become responsible professionals who act in a relevant way in their working situations. In this paper, we describe a three-week study course that we have been teaching since 2012. Students are asked to help people who want to set up a farm, and to practice their reflexivity about this experiment. We have incrementally designed this study course on the basis of learning through our experience, confronting knowledge about education and participating in practice analysis devices. We describe this study-course as an application of interactive social constructivism. Students’ representations are considered as the starting point of our teaching job, socio-cognitive conflicts are encouraged and students’ reflexivity is fostered by simulating professional situations. This study-course has real strengths, but also some weaknesses that require further research. Thus there are debates about which types of knowledge count, and some students do not manage to really practice reflexivity

Destination Auvergne : des acquis de l'image à une logique de marque ?

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Quel avenir pour l’hébergement touristique rural ?

Le succès des formes d’hébergement spécifiques du tourisme rural en France, gîtes ruraux et chambres d’hôtes, ne se dément pas auprès des clientèles touristiques françaises ou européennes. Pourtant les analystes s’interrogent sur l’avenir de ce type d’hébergement, d’une part en raison de mouvements de retrait observés çà et là après une progression continue du parc de gîtes ruraux, d’autre part en raison d’une progression très vive du nombre de chambres d’hôtes, qui risquerait (paradoxalement) de saturer la demande. Les gîtes et les chambres d’hôtes sont-ils des produits, au sens où les définissent les spécialistes en marketing, lorsqu’ils parlent du couple produit-marché ? Les structures d’hébergement touristique sont-elles des entreprises au sens d’organisations complexes, assemblant des activités diversifiées, employant souvent du personnel salarié, recherchant le profit ? Ou sont-elles des formes d’activité mi-domestique, mi-marchande, majoritairement familiale, consubstantielle d’un projet de vie ? Les hébergeurs, enfin, sont-ils animés de l’esprit d’entreprise ou plutôt d’une passion pour les vieilles pierres ? Sont-ils de vrais professionnels du tourisme ou plus généralement des acteurs de la société civile ? Le questionnement sous-jacent à ce travail de recherche-développement, dont la finalité est d’éclairer la décision publique pour accompagner au mieux le développement touristique, s’appuie sur les concepts structurants de l’économie, du marketing et du management (entreprise, produit touristique, professionnalisme), en les soumettant à l’épreuve des faits. L’avenir n’est pas écrit ; il existe en fait des marges de manœuvre. En effet, malgré l’apparence d’une évolution plutôt lente, caractérisée par une demande soutenue évoluant vers une gamme élevée de qualité et une offre prédéterminée par le profil des propriétaires (dominante d’hébergeurs âgés), le parc connaît des mouvements internes considérables d’entrées et de départs. L’étude évolutive et prospective a permis une clarification des données quantitatives et qualitatives sur le parc d’hébergement rural de Gîtes de France du Massif central (gîtes et chambres) et son évolution passée ou future

Designing Housing Benefits: an Application with French Data

With € 18 billion in public expenditure, individual housing benefits account for almost half of the budget for housing policies in France. The effectiveness of this aid has, however, been called into question by a series of empirical studies showing that the majority of it is captured by owners in the form of higher rents. In addition, the interaction of housing benefits with other social benefits strongly reduces work incentives for low-income households. To address these criticisms, we used TAXIPP, the French tax and benefit microsimulation model, to design a reformscenario aimed at restoring the effectiveness of this social policy. We propose combining individual housing benefits with other household assistance measures, in particular the Revenu de solidarité active (RSA – social inclusion benefit) and the Prime pour l’emploi (PPE – earned income tax credit). While respecting the budgetary constraints of the current system, such a reform would considerably simplify the complex architecture of social benefits, reduce the capture of public aid by owners and preserve the gains of a return to paid work while inducing very limited redistributive effects.Élaborer une politique d’aide au logement : microsimulations sur données françaises. Avec 18milliards d’euros de dépenses publiques, les aides personnelles au logement représentent près de la moitié du budget consacré à la politique du logement en France. L’efficacité de ces aides a cependant été remise en cause par une série d’études empiriques qui ont démontré qu’elles étaient en grande partie capturées par les bailleurs sous la forme de loyers plus élevés. Par ailleurs, ces aides pénalisent fortement la reprise d’activité des ménages modestes, en raison de leur mauvaise articulation avec les autres prestations sociales. Pour répondre à ces critiques, nous utilisons le modèle de microsimulation TAXIPP, développé à l’Institut des politiques publiques, pour concevoir un scénario de réforme ayant pour objectif de restaurer l’efficacité de cette politique sociale. Nous proposons de fusionner les aides personnelles au logement avec les autres dispositifs d’aide aux ménages, en particulier le Revenu de solidarité active (RSA) et la Prime pour l’emploi (PPE). En raisonnant à budget constant, une telle réforme permettrait de simplifier considérablement l’architecture des prestations sociales, tout en réduisant la capture des aides par les bailleurs et en préservant les gains à la reprise d’activité.Bozio Antoine, Guillot Malka, Monnet Marion, Romanello Lucile. Designing Housing Benefits: an Application with French Data. In: Économie & prévision, n°211-212, 2017. Evaluation des politiques publiques. Conférence AFSE-DG Trésor du 17 décembre 2015. pp. 163-175

« Cartographier les représentations mentales du risque industriel. Illustration avec les populations de l’estuaire de la Seine – France »

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