Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia : The CREAM Consortium

Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).Peer reviewe

Carbone des sols en Afrique

Les sols sont une ressource essentielle à préserver pour la production d’aliments, de fibres, de biomasse, pour la filtration de l’eau, la préservation de la biodiversité et le stockage du carbone. En tant que réservoirs de carbone, les sols sont par ailleurs appelés à jouer un rôle primordial dans la lutte contre l’augmentation de la concentration de gaz à effet de serre. Ils sont ainsi au centre des objectifs de développement durable (ODD) des Nations unies, notamment les ODD 2 « Faim zéro », 13 « Lutte contre le changement climatique », 15 « Vie terrestre », 12 « Consommation et production responsables » ou encore 1 « Pas de pauvreté ». Cet ouvrage présente un état des lieux des sols africains dans toute leur diversité, mais au-delà, il documente les capacités de stockage de carbone selon les types de sols et leurs usages en Afrique. Il propose également des recommandations autour de l’acquisition et de l’interprétation des données, ainsi que des options pour préserver, voire augmenter les stocks de carbone dans les sols. Tous les chercheurs et acteurs du développement impliqués dans les recherches sur le rôle du carbone des sols sont concernés par cette synthèse collective. Fruit d’une collaboration entre chercheurs africains et européens, ce livre insiste sur la nécessité de prendre en compte la grande variété des contextes agricoles et forestiers africains pour améliorer nos connaissances sur les capacités de stockage de carbone des sols et lutter contre le changement climatique

Particularités des thérapies cognitivo-comportementales et des interventions de psychologie positive dans la prise en charge de la dépression chez les personnes âgées

International audienceSummaryThe increase in psychological and psychiatric consultations by the older adult population, in particular for depressive disorders closely linked with suicide risk [2], calls for effective psychotherapeutic support adapted to the characteristics of this population. Given the lack of research on the effectiveness of psychotherapy for older adults [5], recent studies recognize its success, particularly in the case of cognitive behavioral therapy (CBT) [4]. However, some limitations of CBT with regard to this population require adaptations to their specific needs. Several authors have focused on the adaptation of CBT to the older adult [8], [9], [10], [11]. A complete summary of Evans in 2007 [8] lists the cognitive, sensory and physical disorders which may interfere with therapy and demand particular attention from therapists. The specificity of certain issues, recurring factors or cognitions lead the therapist to adapt the content of the sessions: among other things, issues relating to loss and transition according to Thompson [10], the negative portrayal of old age or anxiety about health [8]. An integrative view appears beneficial in the elderly population. It allows the identification of cognitive schemas, specific to depression in the elderly [17], and typical dysfunctional cognitions, such as the trivialization of depressive symptoms and the inability to change due to aging. An improvement of cognitive restructuring of these cognitions has been proven [18], [19], [20]. At present, adaptations of CBT remain focused on problem areas of the patient, yet work on individual resources would appear to be relevant as a means of optimizing CBT with the older adult.The benefits of positive psychology interventions with the older adultPsychotherapeutic work focusing on positive emotions appears effective [21], [22] and positive psychology interventions (PPIs) are proving to be very promising. Recently, integrated into so-called third wave CBT therapies, these empirically validated approaches focus on positive resources, values and experiences. Their benefits have been shown, particularly in the older adult [24], and demonstrate an improvement in well-being and a decrease in depressive symptoms. However, the few studies in older adults use a limited variety of PPI techniques and are very focused on the past. This should encourage research on existing PPIs to assess and to identify those that are effective, valid and easy to use with the elderly population. Positive psychotherapy (PPT), created by Martin Seligman, is a promising development in this direction. It aims to eliminate psychopathological symptoms and promote happiness and well-being by building positive emotions, reinforcing strength of character and giving meaning to life. Under this approach, emotions and positive forces are as authentic and real as psychopathological symptoms and disorders, and therefore must be fully appreciated. It is complimentary to approaches focusing on the eradication of symptoms. Through more attractive and easy to follow exercises and strategies, it emphasizes the importance of seeking and enhancing positive emotions and strength of character, an important factor in the treatment of the psychopathology [34]. Although not directly concerning the elderly population at present, studies on the effectiveness of PPT show that it is particularly efficient in reducing depressive symptoms and significantly increasing the level of well-being, while reducing the risk of relapse without the need for maintenance sessions.ConclusionWhilst CBT seems effective in the treatment of depression in the older adult, exercises, which are sometimes constraining or even inaccessible, have been adapted to take into account their specificities; it still remains focused on dysfunctions. Yet, work focusing on the resources of the older adult would appear to be useful and efficient. This could be accomplished by PPIs, and in particular PPT, which appear to compliment CBT. The benefits of PPIs and their validity with the elderly population are, therefore, promising areas of research.La population âgée représente aujourd’hui une part de plus en plus considérable des consultations pour troubles dépressifs, d’où l’importance de proposer une prise en charge efficace et optimale. Alors que la thérapie cognitivo-comportementale s’est montrée efficace chez ces patients, elle comporte des limites, d’où la nécessité d’adaptations spécifiques au sujet âgé déprimé. De plus, à l’heure où la psychologie positive et son travail sur les ressources de l’individu s’installent dans les nouvelles techniques thérapeutiques reconnues, des études soulignent leur potentiel important auprès de la population âgée. Ce constat nous interroge sur le rôle des interventions de psychologie positive et de leurs techniques simples et accessibles, qui pourraient apporter des perspectives complémentaires aux thérapies cognitivo-comportementales classiques

Determination of Cl-36 in various radioactive waste

International audienceIntroduction In the context of radioactive waste management, Cl-36 is a key radionuclide to be measured due to its long half-life (3.01x105 years) and its high mobility in the environment. In particular, its mass activi-ty must be lower than 5 Bq/g in France in the packages stored in the disposal facility dedicated to low and intermediate level nuclear waste. Presence of Cl-36 in radwaste mostly results from neutron acti-vation of stable chlorine which can be contained as an impurity in fuels, fuel claddings, graphites and construction materials (steels and concretes).Different strategies developed to extract and purify Cl-36 in radioactive waste Cl-36 decays by emitting a beta particle (98.1 % yield - Emax=708.6 keV) and electron capture (1.9 %). Consequently, this radionuclide can be measured by beta counting techniques, mainly liquid scintilla-tion counting (LSC) for routine analysis of radwaste. As LSC has a poor energy resolution, Cl-36 has to be extracted and isolated from matrix and interfering elements through a selective radiochemical method before any LSC measurement. Radiochemical procedures are generally based on chlorine extraction followed by its precipitation with silver as AgCl and dissolution of this AgCl precipitate with ammonia or implementation of ion-exchange chromatography or extraction chromatography [1]. The method based on AgCl precipitation is relevant for radwaste with low beta- and gamma-emitters and with no other halogens such as iodine (which also precipitates with silver). LASE laboratory (Operator Support Analysis Laboratory) has developed an alternative radiochemical protocol in order to achieve higher decontamination factors required for Cl-36 analysis of high level radioactive samples [2]. After chlorine extraction with various decomposition methods, the following selective purification steps are applied: chlorine precipitation with silver, organic synthesis (chlorine fixation on octadecene), purifica-tion of the chlorinated molecule, then its destruction and an ultimate liquid-liquid extraction. Cl-36 is finally measured by LSC whereas stable chlorine is analyzed by ion chromatography to determine the separation yield.The presentation will give an overview of the different strategies developed to extract and purify Cl-36 in various radioactive waste. The validation of the radiochemical method will first be performed using in-house reference samples spiked with Cl-36 and the participation in interlaboratory comparisons. Different methods applied to extract Cl-36 from various radioactive matrices will then be presented. In particular, implementation of micro-wave digestion, pyrolysis or acid digestion or leaching assisted with digital autoradiography will be explained depending on the studied matrices: ion exchange resins, graphites, concretes, irradiated or surface-contaminated steels and magnesium claddings. Finally, the presentation will discuss with the adaptation of the radiochemical procedure to measure Cl-36 by ac-celerator mass spectrometry (AMS) in order to achieve a detection limit lower than 5 Bq/g. ConclusionCl-36 can be determined with accuracy and high sensitivity in different types of radioactive waste. The performances achieved for Cl-36 are largely suitable for the monitoring of nuclear waste in disposal facilities

Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

International audienceFor decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions

Les circuits d'intercomparaisons : des outils d'amélioration pour la maîtrise de la qualité des analyses

International audienceLe Laboratoire d’Analyses en Soutien aux Exploitants (LASE) au CEA Saclay est chargé de la caractérisation d’effluents et déchets nucléaires des producteurs de déchets du CEA de Saclay, notamment des analyses chimiques et radiologiques. Dans ce cadre, les paramètres physico-chimiques et radiologiques sont analysés avec divers appareils analytiques du laboratoire sur des matrices variées composant les déchets nucléaires telles que des effluents, terres, résines, métaux, huiles et bétons.Du fait de la diversité des échantillons et des différents paramètres à analyser, les circuits d’intercomparaisons permettent de valider nos méthodes, qualifier nos appareils, habiliter le personnel et surtout déterminer l’exactitude des mesures en intégrant les différentes étapes du processus analytique, de la préparation des échantillons jusqu’à l’analyse. Les organisateurs d’intercomparaisons remettent des rapports permettant de situer les performances du LASE par rapport aux valeurs de référence ou de consensus et à celles des autres laboratoires participants. Les résultats du LASE sont analysés en termes de z-scores et d’écarts relatifs par rapport aux valeurs de référence de manière à vérifier la justesse des méthodes et les incertitudes associées.Depuis plus de 10 ans, le LASE participe régulièrement à des circuits d’intercomparaisons organisés par des organismes agréés pour différentes matrices dont l’ensemble balaie la majeure partie des techniques analytiques du laboratoire (environ 20 par an). Ces circuits sont principalement réalisés par des organismes français (AGLAE, BIPEA, CETAMA, LNHB) mais également internationaux (NPL, LGC), ou encore lors de projets européens (INSIDER, NKS).Le retour d’expériences important des circuits d’intercomparaisons auxquels le laboratoire participe, nous permet d’améliorer nos méthodes analytiques mais également de prendre des mesures spécifiques en cas d’éventuels problèmes détectés

DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis

Many endocrine disruptors have been proven to impair the meiotic process that is mandatory to produce healthy gametes. Bisphenol A is emblematic as it impairs meiotic prophase I and causes oocyte aneuploidy following in utero exposure. However, the mechanisms underlying these deleterious effects remain poorly understood. Furthermore, the increasing uses of BPA analogs raise concerns for public health. Here, we investigated the effect on oogenesis in mouse of fetal exposure to two BPA analogs, Bisphenol A Diglycidyl Ether (BADGE) or Bisphenol AF (BPAF). These analogs delay meiosis initiation, increase MLH1 foci per cell and induce oocyte aneuploidy. We further demonstrate that these defects are accompanied by a deregulation of gene expression and aberrant mRNA splicing in fetal premeiotic germ cells. Interestingly, we observed an increase in DNA oxidation after exposure to BPA analogs. Specific induction of oxidative DNA damages during fetal germ cell differentiation causes similar defects during oogenesis, as observed in 8-Oxoguanine DNA Glycosylase (OGG1) deficient mice or after in utero exposure to potassium bromate (KBrO3), an inducer of oxidative DNA damages. Moreover, the supplementation of N-acetylcysteine (NAC) with BPA analogs counteracts the bisphenol-induced meiotic effect. Together our results position oxidative stress as a central event that negatively impacts the female meiosis with major consequences on oocyte quality. This could be a common mechanism of action for so called endocrine disruptors pollutants and it could lead to novel strategies for reprotoxic compounds

Up to 5-year retention of abatacept in Belgian patients with moderate-to-severe rheumatoid arthritis: a sub-analysis of the international, observational ACTION study

Favorable efficacy and safety profiles have been demonstrated for abatacept in patients with rheumatoid arthritis (RA) in randomized controlled trials, but these data require validation during long-term follow-ups in routine clinical practice. This study explored long-term safety and retention rates in RA patients treated with intravenous abatacept in the Belgian cohort of the international AbataCepT In rOutiNe clinical practice (ACTION) study (NCT02109666). This non-interventional, observational, longitudinal study included Belgian patients aged ≥ 18 years with moderate-to-severe RA who started intravenous abatacept treatment as first- or second/further-line biologic therapy in routine clinical practice. Between October 2010 and December 2012, 141 patients were enrolled in this cohort, of whom 135 evaluable patients (6 biologic-naïve; 129 previously exposed to ≥ 1 prior biologic disease modifying anti-rheumatic drugs) were eligible for the descriptive analysis; 131/135 were included in the effectiveness analysis. Mean disease duration was 10.5 years (standard deviation 9.7) before abatacept initiation. RA patients presented with high disease activity and comorbidity rate, having failed multiple previous treatment options. In this cohort, the 5-year abatacept retention rate was 34% (95% confidence interval, 23-45%) per protocol, and 51% (95% confidence interval, 40-61%) when temporary discontinuations of abatacept > 84 days (n = 24) were not considered as treatment discontinuations. After 5 years of abatacept treatment, clinical outcomes were favorable [good/moderate European League Against Rheumatism (EULAR) responses in 91.7% patients]. No new safety signals were detected for abatacept in routine clinical practice. In this difficult-to-treat Belgian RA population, high retention rates, good clinical outcomes and favorable safety profile were observed with abatacept.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Data from: Disruptive viability selection on a black plumage trait associated with dominance

Traits used in communication, such as colour signals, are expected to have positive consequences for reproductive success, but their associations with survival are little understood. Previous studies have mainly investigated linear relationships between signals and survival, but both hump-shaped and U-shaped relationships can also be predicted, depending on the main costs involved in trait expression. Furthermore, few studies have taken the plasticity of signals into account in viability selection analyses. The relationship between signal expression and survival is of particular interest in melanin-based traits, because their main costs are still debated. Here, we first determined the main factors explaining variability in a melanin-based trait linked to dominance: the bib size of a colonial bird, the sociable weaver Philetairus socius. We then used these analyses to obtain a measure representative of the individual mean expression of bib size. Finally, we used capture-recapture models to study how survival varied in relation to bib size. Variation in bib size was strongly affected by year and moderately affected by age, body condition and colony size. In addition, individuals bearing small and large bibs had higher survival than those with intermediate bibs, and this U-shaped relationship between survival and bib size appeared to be more pronounced in some years than others. These results constitute a rare example of disruptive viability selection, and point towards the potential importance of social costs incurred by the dominance signalling function of badges of status