Zur Realisierung individualisierter Produkte halten agile Arbeitsweisen vermehrt Einzug in Prozesse von produzierenden Unternehmen. Dabei ist die Durchdringung agiler Arbeitsweisen durch die etablierten Prozesse in den Entwicklungsabteilungen produzierender Unternehmen aktuell sehr gering; ein Großteil der Unternehmen beginnt jedoch die punktuelle Einführung agiler Arbeitsweisen in ausgewählten Pilotprojekten. Die Anwendung agiler Arbeitsweisen führt in den Prozessen der Entwicklung physischer Systeme zu neuen Herausforderungen und unbekannten Entwicklungsrisiken, die den Vorteilen von Agilität gegenüberstehen. Deswegen ist die Einführung agiler Vorgehensweisen in die Prozesse der Entwicklung physischer Systeme ein Problemlösungsprozess. Die Art, nach der Agilität für einen Anwendungsfall gestaltet wird und in diesen eingeführt wird muss demnach zum Anwendungsfall passen und ist stets individuell. Um diese Individualität in der Einführung agiler Arbeitsweisen zu ermöglichen wurden in Vorarbeiten bereits 228 Faktoren identifiziert, die Einfluss auf die agilen Arbeitsweisen verschiedener Organisationeinheiten haben. Die gezielte Beeinflussung ausgewählter Einflussfaktoren durch geeignete agile Methoden führt zu einer Anwendungsfall-spezifischen Gestaltung und Einführung agiler Vorgehensweisen und erhöht die Eignung des Ansatzes im Vergleich zu einer Anpassungs-freien Einführung. Im vorliegenden Beitrag wird eine Verknüpfung der Faktoren erarbeitet, um Schlüsselfaktoren abzuleiten. Durch die gezielte Beeinflussung dieser soll die Veränderung durch die Einführung agiler Methoden hinsichtlich ihrer Ausbreitung in den Entwicklungskontext gezielt verstärkt werden. Analog zum Szenario Management werden bezüglich der Faktoren mittels einer Vernetzungsanalyse verschiedene Kennzahlen ermittelt. Basierend auf der Analyse kann die Tragweite der Einführung von agilen Methoden genauer eingeschätzt werden und die zielgerichtete Auswahl von agilen Methoden für die Einführung in die Prozesse der physischen Produktentwicklung unterstützt werden.

Autism Spectrum Disorder (ASD) is a neuro-developmental diagnosis that occurs around four times more often in males compared to females. Most of what is known about ASD, as well as diagnostic criteria and screening tools are therefore based on male expressions. Little is known if females differ from males and how female specific expressions of ASD looks like. The aim of this study is therefore to investigate the explanations of the male bias and increase the understanding of these sex differences and female expressions of ASD. My research provides a systematic review of 35 articles that has examined these areas. By conducting a thematic analysis I found that females and males diagnosed with ASD in general show similar expressions but that there is small evidence for female specific expressions. By using the theory of gender stereotyping I am discussing these results and argue that research in the area is caught in a looping effect. The reviewed articles use predominantly male samples while researching sex differences and are therefore reproducing the male bias. Because the stereotypical male expressions persist, females need to express more severe symptoms in order to be detected and correctly diagnosed. I suggest that by increasing the number of female participants in research, the female expression of ASD will be better understood which can aid social workers to detect and provide adequate support and interventions for females. / Autismspektrumtillstånd (AST) är en utvecklingsrelaterad neuro-diagnos som förekommer fyra gånger så ofta hos män som hos kvinnor. Det mesta av den nuvarande kunskapen om ASD samt diagnoskriterier och screening-verktyg är därför baserade på manliga uttryck. Huruvida kvinnor skiljer sig från män och hur kvinnliga uttryck ser ut är fortfarande relativt outforskat. Min studies syfte är att undersöka den manliga snedfördelningen som finns i diagnosen för att öka förståelsen för könsskillnader och kvinnliga ASD uttryck. Detta sker genom en systematisk forskningsöversikt av 35 artiklar som avhandlar nämnda områden. Genom att genomföra en tematisk analys fann jag att kvinnor och män överlag uppvisar liknande uttryck men att det trots det finns bevis för vissa kvinnospecifika uttryck. Jag belyser dessa resultat vidare genom en teori om könsstereotyper och argumenterar för att forskningen på området är fast i en looping-effekt. Då de granskade artiklarna använder övervägande manliga forskningsobjekt när de utforskar könsskillnader så återskapas den manliga snedfördelningen. På grund av detta så fortlever den stereotypiska manliga bilden vilket gör att kvinnor behöver uppvisa starkare symptom för att bli upptäckta och få en korrekt diagnos. Jag föreslår därför att forskningen ökar antalet kvinnliga deltagare så att kvinnliga ASD-uttryck kan bli bättre förstådda vilket kan hjälpa professionella i socialt arbete and enklare upptäcka och bistå med adekvata interventioner och stödprogram för dessa kvinnor.

During the last decade, the number of children diagnosed with Autism Spectrum Disorders (ASD) has increased and more and more children with ASD are educated in inclusive classrooms. Although their inclusion can have several benefits, teachers face some challenges. The main reason is these students’ problem behavior or lack of a desirable behavior. The aim of this systematic literature review was to analyze interventions for behavior management of students with ASD, since the ratification of Salamanca Statement and Framework for Action (UNESCO, 1994), in inclusive preschool and primary school classrooms. The aim was also to examine the outcomes of these interventions. Four databases were searched and nine articles were included for data extraction. Results indicated the implementation of different interventions such as function-based interventions, peer support, visual cue cards, structured teaching with graduated guidance, social stories and social scripts. The target behavior was principally assessed through Functional Behavioral Assessment (FBA) or it was not assessed at all. Some interventions were provided by the researcher or the teacher only, some were provided by different people in different phases and some were provided by two or more people together. Interventions’ goals were to decrease problem behavior, to increase desirable behavior and both to decrease problem behavior and to increase desirable behavior. It was observed that all interventions reached their goals, even though at a low level in some cases. In conclusion, this literature review provided a summary of interventions and their outcomes for behavior management of students with ASD in inclusive classrooms with a further purpose to help the teachers identify the strategies most useful for their classroom.

This study investigates the effects of implementing Collaborative Strategic Reading–High School (CSR–HS) on reading comprehension and challenging behavior outcomes for three high school students with Autism Spectrum Disorder (ASD). Using a combined single subject research design consisting of a delayed, concurrent multiple-baseline and an alternating treatments with reversal, three high school students with ASD were paired with neurotypical reading partners to learn and use reading strategies with informational text two to three times per week. The alternating treatment conditions were CSR-HS with choice of text (i.e., CSR-HS-C) and CSR-HS without the opportunity to choose the reading text (i.e., CSR-HS-NC). Daily comprehension checks were collected and visually inspected along with data on occurrences of various challenging behaviors exhibited by each participant during intervention. Fidelity of implementation was also measured. Increased reading comprehension scores and decreased incidences of challenges behaviors were detected for the three participants upon implementation of intervention conditions. As for the influence of the choice component on the measured outcomes, no clear differentiation between conditions was observed in terms of reading comprehension gains and reduction in challenging behavior across the three participants, suggesting that the addition of choice did not show an added value to CSR-HS intervention. / text

Selective eating (SE) refers to an individual narrowing their range of preferred foods, resulting in a restricted food intake, high levels of rigidity and food refusal (Bryant-Waugh, 2000). SE is encompassed in the new Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) (American Psychiatric Association, 2013) category avoidant restrictive food intake disorder (ARFID). Such difficulties are common in children with an autism spectrum disorder (ASD) (Raiten & Massaro, 1986) and neuropsychological differences have been found in children with ASD (Hill, 2004). This research aimed to be the first to investigate whether a distinct neuropsychological profile exists in children and adolescents with SE and furthermore, whether aspects of the profile vary depending on whether the child or adolescent displays elevated autistic traits. A case series of 10 children between the ages of 8 to 13 years old were recruited. A well-established neuropsychological test battery, the Ravello Profile (Rose, Frampton & Lask, 2012), was modified and administered to assess visuospatial processing, central coherence, executive functions (including cognitive flexibility, inhibition and planning) and theory of mind abilities. The results demonstrated a high degree of variability across the group in terms of visuospatial processing and theory of mind, weak central coherence across all participants and otherwise relatively intact abilities in executive function domains. There were no substantive findings in relation to those children with elevated autistic traits although a trend toward visuospatial processing differences did emerge. This exploratory case series was the first attempt to describe a neuropsychological profile in SE, however the small sample size and high variability in the data meant that a distinct neuropsychological profile did not emerge. The results did however provide an initial indication of possible trends in strengths and weaknesses across neuropsychological domains in SE. These findings have implications for the assessment and treatment of SE difficulties.

Bakgrund: Animal Assisted Therapy (AAT) har i tidigare studier visat sig vara en effektiv metod inom äldrevården och pediatriken för att öka känslan av sammanhang och livskvalité. En person med autism behöver ha en anpassad miljö runtomkring sig för att bibehålla bland annat kognitiva funktioner som i sin tur kan främja hälsa och skapa livskvalité. Ett djur skulle kunna vara ett sätt att anpassa miljön omkring barnet med autism, då det visat sig att djurs närhet har en positiv effekt inom andra vårdområden. Djurterapins huvudområde är att minska sociala, emotionella och kognitiva problem i patientens handlingsplan. När ett barn har någon form av diagnos, blir hela familjen involverad i vården av barnet. Barnet med autism har också särskilt svårt att berätta om sina egna känslor och upplevelser, därför bygger den föreliggande studien på familjernas erfarenheter av djurens betydelse. Syfte: Att beskriva familjers erfarenheter av vilken betydelse djur har för barn med autism. Syftet var också att beskriva den metodologiska aspekten undersökningsgrupp i de inkluderade artiklarna. Metod: En deskriptiv litteraturstudie gjordes. Genom att använda sig av inklusionskriterier, exklusionskriterier och limits, valdes elva artiklar ut - nio kvantitativa och två tvärvetenskapliga - och granskades utifrån frågeställningarna som satts upp. Huvudresultat: Resultatet visade att djurterapi har stor betydelse för barnets sociala förmåga. Även positiva resultat sågs angående kommunikation, problemlösningsförmåga, repetativa beteenden, fysisk styrka och motorik. Undersökningsgrupperna var ojämna, då de hade en ojämn könsfördelning. Slutsats: Resultatet visade att djurterapi haft en positiv betydelse för barn med autism och deras sociala liv. Vidare forskning behövs göras för att göra djurterapi till en evidensbeprövad behandlingsform i framtiden. / Background: Previous research has shown that Animal Assisted Therapy (AAT) is an efficient method to increase the Sense of Coherence and Quality of Life in pediatric- and geriatric care. A person with autism needs to have an adapted environment to maintain cognitive functions which can promote health and promote Quality of Life. In this case, animals could be a means to create environmental adaptation for a child with autism, since animals have proven to have a positive effect on patients in other areas of care. The main purpose of the AAT is to reduce social, emotional and cognitive problems in the care-plan of the child. When a child has some kind of diagnosis, the whole family gets involved in the caring process. The child with autism also have difficulties to share feelings and life experiences. Therefore the present study is based on the experience of families regarding the importance of animals. Aim: To describe families experiences of the importance of animals for children with autism. The aim was also to describe the methodological aspect study group in the included articles. Method: A descriptive literature study was conducted. By using inclusion- and exclusion criterias and limits, eleven articles were chosen – nine with quantitative approach and two with interdiciplinary approach – and were reviewed on the basis of the chosen questions. Main result: The result has shown that AAT is of great importance for the childs social abilities. Also, positive results were shown in communication, problem solving skills, repetative behaviour, physical strength and motor skills. The study groups were uneven, as they had a gender bias. Conclusion: The results showed that AAT have had a positive effect for children with autism and their social life. More research is needed to make AAT an evidential form of treatment in the future.

The purpose of this exploratory study was to examine school psychologists' use of evidence- based practices (EBP), in general, and more specifically in the area of social skills training (SST) for students with autism spectrum disorders (ASD). Study participants, consisting of 498 school psychologists from across the nation, participated in an online survey that gathered information about their training, attitudes, and practices. The frequency with which specific EBP practices for social skills training for students with ASD was examined, as was prediction of use of these practices. Multiple-regression analyses revealed multiple independent variables that were predictors for overall use of EBP. Results indicated that over half of the participants provide SST for students with ASD. Although the majority of participants indicated that their graduate program included at least one course with information about ASD and EBP practices, in general, nearly half indicated that their coursework did not include any courses that directly addressed social skills training for students with ASD. Confirmatory factor analysis (CFA) was used to determine the extent to which the data fit the factor model. Participants' perception of the importance placed on EBP by their school district, scores on the openness subscale of the Evidence Based Practices Assessment Scale, perception of how well their graduate program prepared them in the EBP process, perception of whether they were adequately trained in the area of SST for students with ASD, and having a caseload evenly divided among settings were significant predictors of overall use of EBP.

Direcionar a atenção do aprendiz para diferentes fontes de informação pode afetar a aprendizagem de habilidades motoras. Estudos sugerem que o foco de atenção externo produz melhores efeitos sobre a aprendizagem motora que o foco interno. Este estudo investigou como os diferentes focos de atenção afetam a aprendizagem motora de crianças com autismo. Crianças com diagnóstico de transtorno do espectro do autismo de gravidade leve e moderada (idade média = 11,8 anos), pareadas por idade e massa corporal, foram distribuídas aleatoriamente em dois grupos experimentais para realizar uma tarefa de equilíbrio dinâmico sobre uma plataforma de estabilidade sob instruções de foco externo (N=12) ou interno (N=12). Cada participante realizou seis blocos de cinco tentativas de 20 segundos na fase de aquisição. O desempenho foi avaliado através de medidas de tempo em equilíbrio e número de oscilações da plataforma e a aprendizagem aferida por testes de transferência e retenção. Os resultados demonstraram que não houve diferenças estatisticamente significativas de desempenho entre os grupos de foco externo e interno na fase de aquisição e no teste de transferência (p > 0,05). O desempenho do grupo de foco interno foi marginalmente superior ao grupo de foco externo no teste de retenção (p = 0,087, η² = 0,12). Os resultados demonstraram ainda que os dois grupos aumentaram as respectivas medidas de tempo em equilíbrio, reduziram o número de oscilações e apresentaram menor variabilidade de desempenho ao longo dos blocos de tentativas da fase de aquisição e retiveram as melhorias de desempenho adquiridas no teste de retenção. Essas evidências indicaram que as crianças com autismo foram capazes de aprender a tarefa de equilíbrio dinâmico nas duas condições experimentais propostas e que não é possível afirmar que os efeitos benéficos da adoção do foco de atenção externo em relação ao foco interno na aprendizagem motora sejam generalizáveis para essa população / Directing the learner´s attention to different sources of information can affect the learning of motor skills. Studies suggest that the external focus of attention produces better effects on motor learning than internal focus. This study investigated how different foci of attention affect the motor learning of children with autism. Children diagnosed with autism spectrum disorder of mild to moderate severity (mean age = 11.8 years) matched for age and body mass were randomly assigned to two experimental groups to perform a dynamic equilibrium task on a stability platform under instructions of external (N = 12) or internal (N = 12) focus. Each participant performed six blocks of five 20-second attempts in the acquisition phase. The performance was evaluated through measures of time in equilibrium and number of oscillations of the platform and the learning measured by transfer and retention tests. The results showed that there were no statistically significant differences in performance between the external and internal focus groups in the acquisition phase and in the transfer test (p> 0.05). The performance of the internal focus group was marginally higher than the external focus group in the retention test (p = 0.087, η² = 0.12). The results also demonstrated that the two groups increased their respective time measures in equilibrium, reduced the number of oscillations and presented lower variability of performance throughout the blocks of the acquisition phase and retained the performance improvements obtained in the retention test. These evidences indicated that children with autism were able to learn the task of dynamic balance in the two experimental conditions proposed and that it is not possible to affirm that the beneficial effects of adopting the external attention focus in relation to the internal focus in motor learning are generalizable to population

L’étiologie des troubles du spectre autistique (TSA) est multifactorielle mettant en jeu une forte composante génétique ainsi que des facteurs environnementaux. A ce jour, il n’existe aucun biomarqueur facilitant un diagnostic précoce des TSA, ce qui permettrait une meilleure prise en charge des patients. De plus, les mécanismes physiopathologiques sont encore mal connus. La majorité des études sur les TSA ont été réalisées sur des populations occidentales. Ainsi, nous avons voulu étudier un groupe de patients libanais atteints de TSA. Nos objectifs s’articulent autour de trois volets : 1) L’identification de facteurs de risques environnementaux dans le but de mieux comprendre la pathologie. Les résultats de cette étude ont montré que plusieurs facteurs tels que la consanguinité, le stress au cours de la grossesse et la prématurité semblent être des facteurs de risques. 2) L’identification des variations structurales dans le génome des enfants atteints de TSA afin d'évaluer la contribution de CNV par l'approche de CGH array à haute résolution. Cette étude nous a permis d’identifier de nouveaux gènes dans les TSA ainsi de confirmer la présence des régions et des gènes déjà cités dans des études précédentes sur les TSA. 3) L’identification des métabolites urinaires et des voies métaboliques associés afin de proposer des biomarqueurs aidant à un diagnostic précoce et à une meilleure compréhension de la physiopathologie de la maladie. De nouveaux métabolites ont été identifiés, comme nous avons confirmé des variations anomalies déjà citées dans la littérature concernant certains métabolites qui pourraient représenter des marqueurs robustes de la maladie. / The etiology of autism spectrum disorders (ASD) is multifactorial involving a strong genetic component as well as environmental factors. To date, there is no biomarker facilitating early diagnosis of ASD to improve patient management and outcomes. In addition, the physiopathological mechanisms are still poorly understood. Most studies on ASD have been conducted in Western populations. Thus, we wanted to study a group of Lebanese patients with ASD. Our objectives focus around three aspects: 1) The identification of environmental risk factors in order to better understand the pathology. The results of this study showed that several factors such as consanguinity, stress during pregnancy and prematurity appear to be risk factors. 2) The identification of structural variations in the genome of children with ASD in order to evaluate the contribution of CNV by high resolution CGH array approach. This study allowed us to identify new genes in ASD as well as to confirm the presence of regions and genes already cited in previous ASD studies. 3) The identification of metabolites and associated metabolic pathways to provide biomarkers for early diagnosis and to better understanding of the pathophysiology of the disease. New metabolites have been identified and we have confirmed variations already mentioned in the literature concerning certain metabolites that could represent robust markers of the disease.

Le récepteur 5-HT6 de la sérotonine, un des derniers récepteurs de la sérotonine à avoir été découvert, est une des cibles les plus prometteuses pour traiter les déficits cognitifs de la schizophrénie et de la maladie d’Alzheimer. Les antagonistes 5-HT6 exercent des effets pro-cognitifs dans de nombreux paradigmes expérimentaux de cognition chez les rongeurs et plusieurs d’entre eux sont en développement clinique (phase III) dans la schizophrénie et la maladie d’Alzheimer. Exclusivement exprimé dans le système nerveux central, le récepteur 5-HT6 est présent dès les phases précoces du développement neural et est impliqué dans différents processus neuro-développementaux. Plusieurs études ont ainsi démontré que le récepteur jouait un rôle clé dans la migration des neurones (interneurones et neurones pyramidaux) du cortex cérébral (Riccio et al. Mol Psychiatry 14(3):280-90, 2009 ; Transl Psychiatry 11;1:e47, 2011 ; Jacobshagen et al. Development in revision). Grâce à un crible interactomique, notre équipe a récemment identifié un réseau de protéines recrutées par le domaine carboxy-terminal du récepteur, comprenant la cyclin-dependent kinase (Cdk)5 et certains de ses substrats et connues pour leur implication dans la migration neuronale, la pousse neuritique et la synaptogénèse. Nous avons également démontré que le récepteur stimulait la pousse neuritique de façon agoniste-indépendante par un mécanisme impliquant la phosphorylation du récepteur par Cdk5 et l’activation de la Rho GTPase Cdc42 (Duhr et al. Nature Chem. Biol., en révision). Cette étude a mis pour la première fois en évidence une activation constitutive d’un récepteur couplé aux protéines G dépendant de sa phosphorylation par une kinase associée. Des études préliminaires réalisées par l’équipe indiquent également que l’activation du récepteur 5-HT6 induit une diminution du nombre d’épines dendritiques et une modification de leur morphologie dans des cultures primaires de neurones d’hippocampe. Le projet de thèse aura pour objectif la caractérisation des mécanismes moléculaires impliqués dans cet effet. Une attention particulière sera portée sur le rôle de Cdk5 et de son substrat WAVE1, une protéine induisant la formation des épines dendritiques grâce à sa capacité à activer le complexe Arp2/3 (également identifié dans l’interactome du récepteur 5-HT6) et à promouvoir la polymérisation de l’actine. La phosphorylation de WAVE1 par Cdk5 inhibant son activité et la formation des épines, ce mécanisme pourrait être à l’origine de la diminution du nombre d’épines induite par le récepteur 5-HT6. Ces études seront réalisées in vitro, sur des cultures primaires de neurones d’hippocampe et in vivo, en utilisant un modèle (en cours de génération) de souris knock-in exprimant le récepteur 5-HT6 fusionné à une étiquette GFP. Grâce à ce modèle, un crible interactomique sera également réalisé afin d’identifier de nouveaux partenaires du récepteur potentiellement impliqués dans la différentiation neuronale dans un contexte tissulaire authentique. Ce projet sera réalisé à l’Institut de Génomique Fonctionnelle (IGF) au sein de l’équipe « Neuroprotéomique et signalisation des maladies neurologiques et psychiatriques » sous la co-direction de Philippe Marin et Séverine Chaumont-Dubel. Il permettra de caractériser de nouveaux substrats cellulaires potentiellement impliqués dans les déficits cognitifs de la schizophrénie de plus en plus considérée comme une pathologie du développement et d’identifier de nouvelles cibles pour le traitement précoce de ces déficits particulièrement invalidants et insuffisamment pris en en charge par l’arsenal antipsychotique existant. / The serotonin 5-HT6 receptor, one of the most recently cloned serotonin receptors, is a promising target for the treatment of cognitive deficits of both schizophrenia and Alzheimer’s disease. 5-HT6 receptor blockade by antagonists exerts pro-cognitive effects in a wide range of models of cognitive impairment in rodents and some of them are in phase III of clinical trials in schizophrenia and Alzheimer’s disease. The 5-HT6 receptor is exclusively expressed in the central nervous system, where it is detected at early phases of brain development. Studies have shown that 5-HT6 receptors have a key influence upon migration of both pyramidal neurons and interneurons of the cerebral cortex (Riccio et al. Mol Psychiatry 14(3):280-90, 2009 ; Transl Psychiatry 11;1:e47, 2011; Jacobshagen et al. Development, in revision). Using a proteomic strategy, our team recently identified a network of proteins interacting with the carboxy-terminal domain of the receptor. These include Cyclin-dependent kinase (Cdk)5 and some of its substrates, which are known to control neuro-developmental processes such as neuronal migration, neurite growth and dendritic spine morphogenesis. We have also demonstrated that the expression of the 5-HT6 receptor elicits neurite growth in an agonist-independent manner through a mechanism involving receptor phosphorylation at a serine residue by associated Cdk5 and engagement of the Rho GTPase Cdc42 (Duhr et al. Nature Chem. Biol., in revision). These studies show for the first time a constitutive activation of a G protein-coupled receptor mediated by its phosphorylation by an associated protein kinase. Preliminary experiments performed by the team also revealed that 5-HT6 receptors activation decreases the number of dendritic spines and modify spine morphology in hippocampal neurons in primary culture. This thesis project aims at characterizing the signalling mechanisms underlying the control of dendritic spine morphogenesis by the 5-HT6 receptors. Particular attention will be paid to Cdk5 and its substrate WAVE1, a protein known to induce neurite growth via the activation of the Arp2/3 complex (also identified in the 5-HT6 receptor interactome), which promotes actin polymerization. As phosphorylation of WAVE1 by Cdk5 inhibits its activity, we hypothesize that Cdk5-elicited phosphorylation of WAVE1 in the receptor-associated complex might underlies its control of spine morphogenesis. This project will combine in vitro studies performed on primary cultured hippocampal neurons and in vivo studies using transgenic mice expressing GFP tagged 5-HT6 receptors (this mouse line is currently being generated). We will also take advantage of this model to perform a novel interactomics screen to identify in an authentic tissue context novel receptor partners potentially involved in dendritic spine formation. This project should reveal novel cellular targets for the alleviation of the currently untreated and strongly debilitating cognitive deficits of schizophrenia, which are thought to result from abnormalities of brain development. It will be realized at the Institute of Functional Genomics in the “Neuroproteomics and signaling of neurodegenerative and psychiatric disorders” team under the supervision of Philippe Marin and Séverine Chaumont-Dubel.