'Fracking':Promoter and destroyer of 'the good life'

When discussing the effects of resource extraction in rural communities, academics commonly focus on specific and concrete impacts that fall nicely into the categories of environmental, economic, and social – for example, effects on water quality, jobs, and roads. A less common way of conceptualising effects of extractive industries, but more akin to way in which rural residents discuss and experience the complex set of effects, is changes to way of life. A growing literature explores effects on ‘wellbeing’ and ‘the good life’ as important determinants of responses to development projects, and as necessary considerations for policies regulating such development. One approach to conceptualising the good life – Aristotle’s ideas of eudaimonia (human flourishing) and the pursuit of eudaimonia (perfectionism) – remains underdeveloped as a means for characterising how rural residents respond to natural resource extraction. We use the example of unconventional gas development (UGD) to illustrate how definitions of human flourishing – and perfectionist pursuit of that flourishing – strongly motivate support for and opposition to a contentious extractive industry in the rural communities where development is occurring or is likely to occur (e.g., through commitments to: a rural way of life, retaining local population, beauty, peace, and/or quiet). Approximately fifty interviews across six US and three Canadian communities support this vital role for conceptions of human flourishing. The import of human flourishing to members of the public, and of them pursuing that flourishing through perfectionism, has crucial implications for communication and policy related to extractive development. Policy makers need to consider how the public’s definitions for flourishing shape their support/opposition, and not just to focus on the economic and environmental impacts commonly discussed in policy discourse

Tardive Reactivation of Progressive Multiple Sclerosis During Treatment with Biotin

International audienceMultiple sclerosis (MS) is a common autoimmune disease of the central nervous system, causing neurological disability in young adults. A growing understanding of its immunopathogenesis has led to an expanding array of therapies. Notable new advances in disease-modifying therapies for relapsing forms of multiple sclerosis that are based on anti-inflammatory activity have recently been developed. Management of progressive MS is still challenging. Data published in 2014 suggested that daily high doses of biotin, a vitamin involved in myelin synthesis, might have a beneficial impact on disability and progression in progressive MS. However, some patients worsened while on biotin without any clear explanation for this effect. We report the case of a 41-year-old patient suffering from primary progressive (PP) MS who presented after 16 months of treatment with high doses of biotin (QIZENDAY) with worsening of his Expanding Disability Status Scale (EDSS) score and the appearance of a symptomatic new T2 pseudo-tumoural lesion on brain magnetic resonance imaging (MRI), suggestive of tardive inflammatory reactivation possibly due to the biotin. The newer and more effective therapies for MS are, however, associated with risks that necessitate an active management strategy and continuous vigilance. Physicians should be aware of iatrogenic neurological complications and the possible paradoxical effects of biotin. Future treatment approaches to progressive MS must include identification of a biomarker of disease activity. The study of neurofilaments in the cerebrospinal fluid (CSF) and the serum could be of interest when determining the optimal treatment strategy

Trial of Lixisenatide in Early Parkinson’s Disease

International audienceBackground: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease.Methods: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period. The primary end point was the change from baseline in scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability), which was assessed in patients in the on-medication state at 12 months. Secondary end points included other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent.Results: A total of 156 persons were enrolled, with 78 assigned to each group. MDS-UPDRS part III scores at baseline were approximately 15 in both groups. At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P = 0.007). At 14 months, after a 2-month washout period, the mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) with lixisenatide and 20.6 (95% CI, 18.5 to 22.8) with placebo. Other results relative to the secondary end points did not differ substantially between the groups. Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%.Conclusions: In participants with early Parkinson's disease, lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months in a phase 2 trial but was associated with gastrointestinal side effects. Longer and larger trials are needed to determine the effects and safety of lixisenatide in persons with Parkinson's disease

Les textes médiévaux face à l'édition scientifique contemporaine.

Le texte médiéval est soumis, dans sa construction et sa diffusion, à un travail éditorial qui en modifie nécessairement la nature et la réception. Face à la mouvance du texte au Moyen Âge et devant l’hétérogénéité des pratiques éditoriales médiévales, quels ont été les partis-pris scientifiques de l’édition de ces trente dernières années ? Depuis le xixe siècle, la philologie a connu de nombreuses évolutions : comment le travail éditorial a-t-il intégré, adapté ou rejeté les acquis de ses prédécesseurs ? Par ailleurs, Internet est depuis ces quinze dernières années l’un des principaux vecteurs de transformation de l’édition de textes médiévaux et les enjeux de cette révolution éditoriale n’ont pas encore fait l’objet d’un bilan. La dématérialisation du livre suppose nécessairement une construction et une transmission différente du texte. On pourra notamment se demander dans quelle mesure cet outil parvient ou non à pallier les limites techniques du livre imprimé et à renouveler l’approche de l’objet manuscrit dans ce qu’il a de plus singulier. Cependant, l’édition sur Internet, la numérisation du patrimoine manuscrit et tous les outils électroniques de ressources textuelles qui se développent aujourd’hui n’imposent-ils pas un nouveau mirage ? Le sentiment d’un accès apparemment illimité et sans contrainte à l’objet manuscrit ne produit-il pas de nouveaux écarts interprétatifs entre le texte édité et le manuscrit ? Les contribution qui forment la partie « Études et travaux » de ce premier numéro en ligne de Perspectives médiévales apportent des éléments de réponse et des éclairages à ces questionnement qui traversent l’histoire et les pratiques contemporaines de l’édition des textes médiévaux. Sébastien Douche

Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

International audienceAbstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE -ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1 -LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1- LoF variants, stratified by APOE-ε4 , derived from the Rotterdam study ( N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1- LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE -ε4-stratified SORL1- LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1- LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE -ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1- LoF variant carriers in case-control study data. Conclusions We conclude that SORL1- LoF variants should be interpreted in light of APOE genotypes for future clinical applications

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed