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BACKGROUND: A rapid and affordable point-of-care test is a priority for Neisseria gonorrhoeae control. WHO and Foundation for Innovative New Diagnostics (FIND) have a target product profile for a non-molecular N gonorrhoeae rapid point-of-care test that requires a clinical sensitivity of greater than 80% and a specificity over 95% to be considered useful in syndromic management; test turnaround time should be 30 min or under, and the test should cost less than US$3. A novel lateral flow assay (LFA) was developed to achieve that profile. METHODS: In this cross-sectional study we evaluated the performance of the novel N gonorrhoeae lateral flow assay (NG-LFA) at the primary health-care level in South Africa. Male patients with urethral discharge syndrome and female patients with vaginal discharge syndrome were recruited from five primary health-care facilities in the Buffalo City Metropolitan Municipality health district of South Africa. First-void urine specimens and nurse-collected vaginal swabs were tested in-facility with the NG-LFA and Xpert CT/NG PCR assay. N gonorrhoeae multi-antigen sequence typing (NG-MAST) was performed on all LFA positive specimens. FINDINGS: Between March 7, and Sept 19, 2022, we enrolled 200 male patients with urethral discharge and 200 female patients with vaginal discharge. The median age of male patients was 24 years (IQR 21-31 years), and the median age of female patients was 25 years (IQR 21-32 years). In addition, 23 male patients and 12 female patients who presented at the facility with a partner notification slip were enrolled of whom one (4%) and five (42%) were symptomatic, respectively. NG-LFA and Xpert results were available for all participants. In urine specimens, NG-LFA sensitivity was 96·1% (Wilson 95% CI 91·2-98·3; 123 LFA-positive among 128 PCR-positive specimens) and 91·7% in vaginal swab specimens (78·2-97·1; 33 LFA-positive among 36 PCR-positive). The specificity was 97·2% in urine specimens (90·4-99·2; 70 LFA-negativ

Understanding the impact of splicing and nonsense variants on RNA is crucial for the resolution of variant classification as well as their suitability for precision medicine interventions. This is primarily enabled through RNA studies involving transcriptomics followed by targeted assays using RNA isolated from clinically accessible tissues (CATs) such as blood or skin of affected individuals. Insufficient disease gene expression in CATs does however pose a major barrier to RNA based investigations, which we show is relevant to 1,436 Mendelian disease genes. We term these "silent" Mendelian genes (SMGs), the largest portion (36%) of which are associated with neurological disorders. We developed two approaches to induce SMG expression in human dermal fibroblasts (HDFs) to overcome this limitation, including CRISPR-activation-based gene transactivation and fibroblast-to-neuron transdifferentiation. Initial transactivation screens involving 40 SMGs stimulated our development of a highly multiplexed transactivation system culminating in the 6- to 90,000-fold induction of expression of 20/20 (100%) SMGs tested in HDFs. Transdifferentiation of HDFs directly to neurons led to expression of 193/516 (37.4%) of SMGs implicated in neurological disease. The magnitude and isoform diversity of SMG expression following either transactivation or transdifferentiation was comparable to clinically relevant tissues. We apply transdifferentiation and/or gene transactivation combined with short- and long-read RNA sequencing to investigate the impact that variants in USH2A, SCN1A, DMD, and PAK3 have on RNA using HDFs derived from affected individuals. Transactivation and transdifferentiation represent rapid, scalable functional genomic solutions to investigate variants impacting SMGs in the patient cell and genomic context.

The modification, by exotic sources of cooling, of the neutrino burst's duration following the core collapse of SN 1987A is known to provide a formidable constraint on axion interactions with matter. Compton-like nucleon-pion to nucleon-axion scattering has recently been shown to be an important mechanism, due to the large baryon and the non-negligible pion densities in the concerned proto-neutron star volume. In this context, the question arises of the role of hadronic matter beyond the first generation -- in particular strange matter. We perform a first quantitative study of this question, by consistently including the full baryon and meson octets in axion emission from Compton-like scattering and from baryon decay. We consider a range of possible thermodynamic conditions in the SN as well as various scenarios for the axion-quark couplings -- among them an "agnostic" scenario bounded only by data. Irrespective of the scenario considered, we find that axion emissivity introduces non-trivial correlations between flavour-diagonal axial couplings and constrains the off-diagonal counterpart to $O(10^{-1}$-$10^{-2})$ for $f_a = 10^9$ GeV., Comment: 10 pages, 2 figures

DYRK1A Syndrome (OMIM #614104) is caused by pathogenic variations in the DYRK1A gene located on 21q22. Haploinsufficiency of DYRK1A causes a syndrome with global psychomotor delay and intellectual disability. Low birth weight, growth restriction with feeding difficulties, stature insufficiency, and microcephaly are frequently reported. This study aims to create specific growth charts for individuals with DYRK1A Syndrome and identify parameters for size prognosis. Growth parameters were obtained for 92 individuals with DYRK1A Syndrome (49 males vs. 43 females). The data were obtained from pediatric records, parent reporting, and scientific literature. Growth charts for height, weight, body mass index (BMI), and occipitofrontal circumference (OFC) were generated using generalized additive models through R package gamlss. The growth curves include height, weight, and OFC measurements for patients aged 0-5 years. In accordance with the literature, the charts show that individuals are more likely to present intrauterine growth restriction with low birth weight and microcephaly. The growth is then characterized by severe microcephaly, low weight, and short stature. This study proposes growth charts for widespread use in the management of patients with DYRK1A syndrome.

The life history strategies of soil microbes determine their metabolic potential and their response to environmental changes. Yet these strategies remain poorly understood. Here we use shotgun metagenomes from terrestrial biomes to characterize overarching covariations of the genomic traits that capture dominant life history strategies in bacterial communities. The emerging patterns show a triangle of life history strategies shaped by two trait dimensions, supporting previous theoretical and isolate-based studies. The first dimension ranges from streamlined genomes with simple metabolisms to larger genomes and expanded metabolic capacities. As metabolic capacities expand, bacterial communities increasingly differentiate along a second dimension that reflects a trade-off between increasing capacities for environmental responsiveness or for nutrient recycling. Random forest analyses show that soil pH, C:N ratio and precipitation patterns together drive the dominant life history strategy of soil bacterial communities and their biogeographic distribution. Our findings provide a trait-based framework to compare life history strategies of soil bacteria.

Avez-vous l'impression de "vous prendre la tête" sur des sujets qui n'en valent pas toujours la peine ? D'être submergé par un flot de ruminations ininterrompu ? Et si ce n'était pas une fatalité ? Grâce au programme personnalisé, simple et efficace imaginé par Gaëlle Piton, vous allez enfin apprivoiser votre mental et en faire un allié. "Quel ruminateur/trice êtes-vous ?"Découvrez votre profil à travers un psycho-test, puis apprenez à repérer et à prendre conscience de vos pensées parasites, pour ensuite mieux les accueillir et les transformer ! Selon le temps dont vous disposez, vous choisirez les outils et le challenge de 21 jours le plus adapté : 5, 15 ou 30 minutes par jour.Ce livre vous accompagnera pas à pas dans votre quête d'apaisement mental grâce à de nombreuses pratiques dont : des exercices de coaching et de développement personnel (Tipi, Ho'oponopono...) ; des pratiques psychocorporelles (chant, danse, sophrologie, cohérence cardiaque...) ; des outils créatifs et d'intuition ; des conseils bien-être... En acceptant de relever ce défi, à votre rythme, vous allez enfin vous libérer de vos ruminations et atteindre la sérénité ! 21 jours pour transformer ses pensées parasites !

Objective: To understand the perception of the Nursing team about institutional violence against hospitalized children. Materials and method: A qualitative, descriptive and exploratory study, performed at a large-size public hospital in Salvador, Bahia, Brazil, with 17 Nursing professionals working in the Pediatrics unit, to whom semi-structured interviews were applied between March and May 2019. The collected data were categorized in the NVIVO12 software and submitted for content analysis. Results: The results are presented in four categories: The professionals’ lack of knowledge about institutional violence against hospitalized children; Recognition of institutional violence related to problems in the hospital infrastructure, Recognition of institutional violence in interpersonal relationships and Recognition of institutional violence in the care practices. Conclusions: It becomes necessary to apply policies to confront institutional violence, ranging from training the professionals to adapting the spaces and care practices to favor the children’s hospitalization environment., Objetivo: compreender a percepção da equipe de enfermagem sobre a violência institucional contra a criança hospitalizada. Materiais e método: estudo qualitativo, descritivo e exploratório, realizado em hospital público de grande porte, em Salvador, Bahia, Brasil, com 17 profissionais de enfermagem que atuavam na unidade pediátrica, com os quais foi aplicada entrevista semiestruturada, entre março e maio de 2019. Os dados coletados foram categorizados no software NVIVO12 e submetidos à análise de conteúdo. Resultados: os resultados são apresentados em quatro categorias — o desconhecimento dos profissionais sobre violência institucional contra a criança hospitalizada; o reconhecimento da violência institucional relacionada aos problemas na infraestrutura hospitalar; nas relações interpessoais e nas práticas de cuidado. Conclusões: faz-se necessária a aplicação de políticas para o enfrentamento da violência institucional que vão desde o treinamento de profissionais até a adequação de espaços e práticas de cuidado como forma de favorecer o ambiente em que a criança se encontra hospitalizada., Objetivo: comprender la percepción del equipo de enfermería acerca de la violencia institucional hacia el niño hospitalizado. Materiales y método: estudio cualitativo, descriptivo y exploratorio, realizado en hospital público de gran tamaño, en Salvador, Bahia, Brasil, a 17 profesionales de enfermería que actuaban en la unidad pediátrica, a quienes se aplicó entrevista semiestructurada, entre marzo y mayo de 2019. Se recolectaron los datos, los que se categorizaron en el software NVIVO12 y se sometieron a análisis de contenido. Resultados: se presentan los resultados en cuatro categorías — el desconocimiento de los profesionales acerca de la violencia institucional hacia el niño hospitalizado; el reconocimiento de la violencia institucional relacionada a los problemas en la infraestructura hospitalaria; en las relaciones interpersonales y en las prácticas de cuidado. Conclusiones: es necesaria la aplicación de políticas para hacer frente a la violencia institucional que van desde la capacitación de profesionales hasta la adecuación de espacios y prácticas de cuidado como forma de favorecer el entorno en que el niño se encuentra hospitalizado.

Dark kitchen is a delivery-only restaurant that operates without direct contact with the consumer, has no premises for local consumption and sells exclusively through online platforms. The main objective of this work is to identify and characterise dark kitchens in three urban centres featured in the most used food delivery app in Brazil. To this end, data collection was conducted in two phases. In the first phase, through data mining, we collected information from restaurants in three cities (Limeira, Campinas, and São Paulo - Brazil) that were provided in the food delivery app. A total of 22,520 establishments were searched from the central point of each of the cities. In the second phase, the first 1,000 restaurants in each city were classified as dark kitchens, standard, or undefined restaurants. A thematic content analysis was conducted to further distinguish the dark kitchen models. Of the restaurants evaluated, 1,749 (65.2%) were classified as standard restaurants, 727 (27.1%) as dark kitchens, and 206 (7.7%) as undefined. In terms of the characteristics of dark kitchens, they were more dispersed and located further away from the central points compared to standard restaurants. Meals in dark kitchens were cheaper than in standard restaurants, and had a lower number of user reviews. Most of the dark kitchens in São Paulo served Brazilian dishes, while in the smaller cities, Limeira and Campinas, it was mainly snacks and desserts. Six different models of dark kitchen were identified: Independent dark kitchen; shell-type (hub); franchise; virtual kitchen in a standard restaurant (different menu); virtual kitchen in a standard restaurant (similar menu but different name); and home-based dark kitchen. The modelling approach and methodology used to classify and identify dark kitchens is considered a contribution to science as it allows a better understanding of this fast growing sector of the food industry. This in turn can help to develop management strategies and

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a shift of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

01 februari 2023, Item does not contain fulltext, Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

Item does not contain fulltext, Intellectual disability with or without manifestations of autism and/or epilepsy affects 1-2% of the population, and it is estimated that more than 30-50% of these cases have a single genetic cause. More than 1000 genes and recurrent chromosomal abnormalities are involved in these genetic forms of neurodevelopmental disorders, which often remain insufficiently described in terms of clinical spectrum, associated medical problems, etc., due to their rarity and the often-limited number of patients' phenotypes reported. GenIDA is an international online participatory database that aims to better characterise the clinical manifestations and natural histories of these rare diseases. Clinical information is reported by parents of affected individuals using a structured questionnaire exploring physical parameters, cognitive and behavioural aspects, the presence or absence of neurological disorders or problems affecting major physiological functions, as well as autonomy and quality of life. This strengthens the implication in research of the concerned families. GenIDA aims to construct international cohorts of significant size of individuals affected by a given condition. As of July 2022, GenIDA counts some 1545 documented patient records from over 60 nationalities and collaborates with clinicians and researchers around the world who have access to the anonymized data collected to generate new, medically meaningful information to improve patient care. We present the GenIDA database here, together with an overview of the possibilities it offers to affected individuals, their families, and professionals in charge of the management of genetic forms of neurodevelopmental disorders. Finally, case studies of cohorts will illustrate the usefulness of GenIDA.

Contains fulltext : 294552.pdf (Publisher’s version ) (Open Access), PURPOSE: To characterize a novel neurodevelopmental syndrome due to loss-of-function (LoF) variants in Ankyrin 2 (ANK2), and to explore the effects on neuronal network dynamics and homeostatic plasticity in human-induced pluripotent stem cell-derived neurons. METHODS: We collected clinical and molecular data of 12 individuals with heterozygous de novo LoF variants in ANK2. We generated a heterozygous LoF allele of ANK2 using CRISPR/Cas9 in human-induced pluripotent stem cells (hiPSCs). HiPSCs were differentiated into excitatory neurons, and we measured their spontaneous electrophysiological responses using micro-electrode arrays (MEAs). We also characterized their somatodendritic morphology and axon initial segment (AIS) structure and plasticity. RESULTS: We found a broad neurodevelopmental disorder (NDD), comprising intellectual disability, autism spectrum disorders and early onset epilepsy. Using MEAs, we found that hiPSC-derived neurons with heterozygous LoF of ANK2 show a hyperactive and desynchronized neuronal network. ANK2-deficient neurons also showed increased somatodendritic structures and altered AIS structure of which its plasticity is impaired upon activity-dependent modulation. CONCLUSIONS: Phenotypic characterization of patients with de novo ANK2 LoF variants defines a novel NDD with early onset epilepsy. Our functional in vitro data of ANK2-deficient human neurons show a specific neuronal phenotype in which reduced ANKB expression leads to hyperactive and desynchronized neuronal network activity, increased somatodendritic complexity and AIS structure and impaired activity-dependent plasticity of the AIS.

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis., Funding Agencies|Fondazione AIRC per la Ricerca sul Cancro [IG 21558]; Italian Ministry for University and Research (MIUR) [PRIN 20174TB8KW]; FWO [1861419N]; Queen Elisabeth Medical Foundation; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [418081722, 433158657]; CPA grant [PG01217]; NHMRC Principal Research Fellowship [GNT1120615]; BICARE, Australia; King Salman Center for Disability Research [RG-2022-010, RG-2022-011]; MRC [MR/T007087/1]; GOSH Charity [VS0122]; Rosetrees Trust [CF2\100018]; NHMRC Investigator Grant [GNT20081]; Projekt DEAL; NIHR GOSH BRC

Dark kitchen is a delivery-only restaurant that operates without direct contact with the consumer, has no premises for local consumption and sells exclusively through online platforms. The main objective of this work is to identify and characterise dark kitchens in three urban centres featured in the most used food delivery app in Brazil. To this end, data collection was conducted in two phases. In the first phase, through data mining, we collected information from restaurants in three cities (Limeira, Campinas, and São Paulo - Brazil) that were provided in the food delivery app. A total of 22,520 establishments were searched from the central point of each of the cities. In the second phase, the first 1,000 restaurants in each city were classified as dark kitchens, standard, or undefined restaurants. A thematic content analysis was conducted to further distinguish the dark kitchen models. Of the restaurants evaluated, 1,749 (65.2%) were classified as standard restaurants, 727 (27.1%) as dark kitchens, and 206 (7.7%) as undefined. In terms of the characteristics of dark kitchens, they were more dispersed and located further away from the central points compared to standard restaurants. Meals in dark kitchens were cheaper than in standard restaurants, and had a lower number of user reviews. Most of the dark kitchens in São Paulo served Brazilian dishes, while in the smaller cities, Limeira and Campinas, it was mainly snacks and desserts. Six different models of dark kitchen were identified: Independent dark kitchen; shell-type (hub); franchise; virtual kitchen in a standard restaurant (different menu); virtual kitchen in a standard restaurant (similar menu but different name); and home-based dark kitchen. The modelling approach and methodology used to classify and identify dark kitchens is considered a contribution to science as it allows a better understanding of this fast growing sector of the food industry. This in turn can help to develop management strategies and

Dark kitchen is a delivery-only restaurant that operates without direct contact with the consumer, has no premises for local consumption and sells exclusively through online platforms. The main objective of this work is to identify and characterise dark kitchens in three urban centres featured in the most used food delivery app in Brazil. To this end, data collection was conducted in two phases. In the first phase, through data mining, we collected information from restaurants in three cities (Limeira, Campinas, and São Paulo - Brazil) that were provided in the food delivery app. A total of 22,520 establishments were searched from the central point of each of the cities. In the second phase, the first 1,000 restaurants in each city were classified as dark kitchens, standard, or undefined restaurants. A thematic content analysis was conducted to further distinguish the dark kitchen models. Of the restaurants evaluated, 1,749 (65.2%) were classified as standard restaurants, 727 (27.1%) as dark kitchens, and 206 (7.7%) as undefined. In terms of the characteristics of dark kitchens, they were more dispersed and located further away from the central points compared to standard restaurants. Meals in dark kitchens were cheaper than in standard restaurants, and had a lower number of user reviews. Most of the dark kitchens in São Paulo served Brazilian dishes, while in the smaller cities, Limeira and Campinas, it was mainly snacks and desserts. Six different models of dark kitchen were identified: Independent dark kitchen; shell-type (hub); franchise; virtual kitchen in a standard restaurant (different menu); virtual kitchen in a standard restaurant (similar menu but different name); and home-based dark kitchen. The modelling approach and methodology used to classify and identify dark kitchens is considered a contribution to science as it allows a better understanding of this fast growing sector of the food industry. This in turn can help to develop management strategies and

Little is known about dispersal in deep-sea ecosystems, especially for sponges, which are abundant ecosystem engineers. Understanding patterns of gene flow in deep-sea sponges is essential, especially in areas where rising pressure from anthropogenic activities makes difficult to combine management and conservation. Here, we combined population genomics and oceanographic modelling to understand how Northeast Atlantic populations (Cantabrian Sea to Norway) of the deep-sea sponge Phakellia ventilabrum are connected. The analysis comprised ddRADseq derived SNP datasets of 166 individuals collected from 57 sampling stations from 17 different areas, including two Marine Protected Areas, one Special Area of Conservation and other areas with different levels of protection. The 4,017 neutral SNPs used indicated high connectivity and panmixis amongst the majority of areas (Ireland to Norway), spanning ca. 2,500-km at depths of 99–900 m. This was likely due to the presence of strong ocean currents allowing long-distance larval transport, as supported by our migration analysis and by 3D particle tracking modelling. On the contrary, the Cantabrian Sea and Roscoff (France) samples, the southernmost areas in our study, appeared disconnected from the remaining areas, probably due to prevailing current circulation patterns and topographic features, which might be acting as barriers for gene flow. Despite this major genetic break, our results suggest that all protected areas studied are well-connected with each other. Interestingly, analysis of SNPs under selection replicated results obtained for neutral SNPs. The relatively low genetic diversity observed along the study area, though, highlights the potential fragility of this species to changing climates, which might compromise resilience to future threats.

A growing portion of scientists realises the need to not only alert about climate change, but also change their professional practices. A range of tools have emerged to promote more sustainable activities, yet many scientists struggle to go beyond simple awareness-raising to create concrete transition actions. Here we propose a game-based transition support system MaTerre180', which has been designed to build scenarios of greenhouse gas (GHG) emission reductions in the academic community. After providing a common scientific background about the context (global warming issue, its causes and consequences) and setting up a challenge (50% reduction of carbon budget by 2030), the participants belonging to the academic community and its governance bodies immerse themselves into fictional characters, to simulate the behaviour of real research groups. The game has been deployed during the year 2021, with six hundred participants from nine countries and 50 cities. Results explore clear pathways for GHG reductions between 25 and 60%, and a median reduction of 46%. The alternatives allowing the greatest reduction are video communication tools (36%), followed by mutualization of professional activities and voluntary cancellation or reduction, that represent 22 and 14% of reduction, respectively. The remaining 28% of reduction consists of transport alternative, relocation of professional activities, extended duration of some travels, etc. In addition, the analyses pointed out the importance of the guided negotiation phase to bring out some alternatives such as relocation, local partners and computing optimization. An added value of this transition support system is that the information it collects (anonymously) will be used to answer pressing research questions in climate change science and environmental psychology regarding the use of serious games for promoting changes in attitudes and behaviours towards sustainability, and including broader questions on how network structures

Despite the potential of subsoil carbon (C) to buffer or amplify climate change impacts, how fresh C and nutrients interact to control microorganismal effects on the C balance in deep soil horizons has yet to be determined. In this study, we aimed to estimate the impact of fresh C input at different soil depths on soil microbial activity. To conduct this study, Mediterranean soils from 3 layers (0–20, 20–50 and 50–100 cm of depth) were incubated over 28 days. Carbon and nutrient fluxes were measured after the addition of an amount of C equivalent to the postharvest root litter derived-C of a barley crop (4.3 atom% 13C), with and without nitrogen and phosphorus supply. We found that the microbial mineralization was C limited in the topsoil, while C and N colimited in the subsoil. These variations in stoichiometric constraints along the soil profile induced different microbial responses to C and/or nutrient addition. A stronger priming effect was observed in the topsoil than in the subsoil, and the sole C addition induced a negative C balance. Conversely, subsoil showed a positive C balance following fresh C addition, changing to critical soil C losses when nutrients were supplied with C. Our results show that fresh C input to subsoil (e.g., through deep-rooting crops) might foster soil C sequestration, but this positive effect can be reversed if such C inputs are combined with high nutrient availability (e.g., through fertilization), alleviating microbial limitation at depth.

[EN] River widening, defined as a lateral expansion of the channel, is a critical process that maintains fluvial ecosystems and is part of the regular functioning of rivers. However, in areas with high population density, channel widening can cause damage during floods. Therefore, for effective flood risk management it is essential to identify river reaches where abrupt channel widening may occur. Despite numerous efforts to predict channel widening, most studies have been limited to single rivers and single flood events, which may not be representative of other conditions. Moreover, a multi-catchment scale approach that covers various settings and flood magnitudes has been lacking. In this study, we fill this gap by compiling a large database comprising 1564 river reaches in several mountain regions in Europe affected by floods of varying magnitudes in the last six decades. By applying a meta-analysis, we aimed to identify the types of floods responsible for more extensive widening, the river reach types where intense widening is more likely to occur, and the hydraulic and morphological variables that explain widening and can aid in predicting widening. Our analysis revealed seven groups of reaches with significantly different responses to floods regarding width ratios (i.e., the ratio between channel width after and before a flood). Among these groups, the river reaches located in the Mediterranean region and affected by extreme floods triggered by short and intense precipitation events showed significantly larger widening than other river reaches in other regions. Additionally, the meta-analysis confirmed valley confinement as a critical morphological variable that controls channel widening but showed that it is not the only controlling factor. We proposed new statistical models to identify river reaches prone to widening, estimate potential channel width after a flood, and compute upper bound width ratios. These findings can inform flood hazard evaluations and t

LinkedIn est le réseau professionnel qui monte et devient un passage obligé pour toute stratégie de visibilité business. Vous voulez convaincre vos prospects de faire appel à vos services mais vous ne savez pas comment vous y prendre ? Vous souhaitez créer une communauté engagée, qui vous ressemble ? Vous rêvez de devenir une référence sur votre secteur ? Christopher Piton vous révèle ici toutes les méthodes pour développer votre activité sur LinkedIn même si vous démarrez de zéro et n’avez aucune compétence technique. S’appuyant sur de nombreux exemples et témoignages, cet ouvrage donne toutes les clés pour décoller sur LinkedIn et reste valable quelles que soient les mises à jour. 1.Trouvez votre positionnement : misez sur les fondamentaux pour mieux (vous) vendre et identifiez votre client idéal. 2.Déployez une stratégie marketing efficace : découvrez comment gagner la confiance d’un parfait inconnu sur LinkedIn et comment construire un réseau de contacts à votre image et au service de votre business. 3.Créez des contenus qui font mouche : utilisez des méthodes concrètes pour raconter des histoires captivantes et véhiculer vos messages avec plus d’émotions. 4.Devenez la personne à contacter : apprenez à donner de la personnalité à vos contenus et mettez en place une routine pour générer des prospects en continu.

LinkedIn est le réseau professionnel qui monte et devient un passage obligé pour toute stratégie de visibilité business. Vous voulez convaincre vos prospects de faire appel à vos services mais vous ne savez pas comment vous y prendre ? Vous souhaitez créer une communauté engagée, qui vous ressemble ? Vous rêvez de devenir une référence sur votre secteur ? Christopher Piton vous révèle ici toutes les méthodes pour développer votre activité sur LinkedIn même si vous démarrez de zéro et n’avez aucune compétence technique. S’appuyant sur de nombreux exemples et témoignages, cet ouvrage donne toutes les clés pour décoller sur LinkedIn et reste valable quelles que soient les mises à jour. 1.Trouvez votre positionnement : misez sur les fondamentaux pour mieux (vous) vendre et identifiez votre client idéal. 2.Déployez une stratégie marketing efficace : découvrez comment gagner la confiance d’un parfait inconnu sur LinkedIn et comment construire un réseau de contacts à votre image et au service de votre business. 3.Créez des contenus qui font mouche : utilisez des méthodes concrètes pour raconter des histoires captivantes et véhiculer vos messages avec plus d’émotions. 4.Devenez la personne à contacter : apprenez à donner de la personnalité à vos contenus et mettez en place une routine pour générer des prospects en continu.

LinkedIn est le réseau professionnel qui monte et devient un passage obligé pour toute stratégie de visibilité business. Vous voulez convaincre vos prospects de faire appel à vos services mais vous ne savez pas comment vous y prendre ? Vous souhaitez créer une communauté engagée, qui vous ressemble ? Vous rêvez de devenir une référence sur votre secteur ? Christopher Piton vous révèle ici toutes les méthodes pour développer votre activité sur LinkedIn même si vous démarrez de zéro et n’avez aucune compétence technique. S’appuyant sur de nombreux exemples et témoignages, cet ouvrage donne toutes les clés pour décoller sur LinkedIn et reste valable quelles que soient les mises à jour. 1.Trouvez votre positionnement : misez sur les fondamentaux pour mieux (vous) vendre et identifiez votre client idéal. 2.Déployez une stratégie marketing efficace : découvrez comment gagner la confiance d’un parfait inconnu sur LinkedIn et comment construire un réseau de contacts à votre image et au service de votre business. 3.Créez des contenus qui font mouche : utilisez des méthodes concrètes pour raconter des histoires captivantes et véhiculer vos messages avec plus d’émotions. 4.Devenez la personne à contacter : apprenez à donner de la personnalité à vos contenus et mettez en place une routine pour générer des prospects en continu.

LinkedIn est le réseau professionnel qui monte et devient un passage obligé pour toute stratégie de visibilité business. Vous voulez convaincre vos prospects de faire appel à vos services mais vous ne savez pas comment vous y prendre ? Vous souhaitez créer une communauté engagée, qui vous ressemble ? Vous rêvez de devenir une référence sur votre secteur ? Christopher Piton vous révèle ici toutes les méthodes pour développer votre activité sur LinkedIn même si vous démarrez de zéro et n’avez aucune compétence technique. S’appuyant sur de nombreux exemples et témoignages, cet ouvrage donne toutes les clés pour décoller sur LinkedIn et reste valable quelles que soient les mises à jour. 1.Trouvez votre positionnement : misez sur les fondamentaux pour mieux (vous) vendre et identifiez votre client idéal. 2.Déployez une stratégie marketing efficace : découvrez comment gagner la confiance d’un parfait inconnu sur LinkedIn et comment construire un réseau de contacts à votre image et au service de votre business. 3.Créez des contenus qui font mouche : utilisez des méthodes concrètes pour raconter des histoires captivantes et véhiculer vos messages avec plus d’émotions. 4.Devenez la personne à contacter : apprenez à donner de la personnalité à vos contenus et mettez en place une routine pour générer des prospects en continu.

This study aims to discuss the use of multiple layers of defence to prevent foodborne illness in restaurants. A defence model was developed based on Reason’s Swiss Cheese Model. Reason’s model was extended by adding the concept of Hazard Analysis and Critical Control Points, as well as Five Keys to Safer Food. The defence system was divided into seven layers of defence: 1) adequate facilities and 2) training as administrative controls; 3) safe ingredients and water; 4) environmental hygiene; 5) personal and food hygiene and 6) safe food temperature as behavioural controls; and 7) control and systems. The hypothesis was that the layers would act as barriers to prevent hazards from causing losses. To test the model, a dataset (secondary data) of food safety assessments from 1,536 different restaurant establishments in Brazil was used. A checklist of 51 items was organised into seven layers of defence system. The model was tested with a Partial Least Square Structural Equation Model. Errors in administrative controls (facilities and training) led to errors in behavioural controls. A 'cascade effect' was observed where errors in distal behavioural controls (safe ingredients and water and environmental hygiene) impacted proximal controls (personal and food hygiene and; safe food temperature) and system controls. It was discussed how latent conditions and active failures can string together and cause a foodborne illness incident. The Swiss Cheese Model of food safety incidents is proposed as a new perspective for food safety. This model can be used for risk management and food safety education.

This study aims to discuss the use of multiple layers of defence to prevent foodborne illness in restaurants. A defence model was developed based on Reason’s Swiss Cheese Model. Reason’s model was extended by adding the concept of Hazard Analysis and Critical Control Points, as well as Five Keys to Safer Food. The defence system was divided into seven layers of defence: 1) adequate facilities and 2) training as administrative controls; 3) safe ingredients and water; 4) environmental hygiene; 5) personal and food hygiene and 6) safe food temperature as behavioural controls; and 7) control and systems. The hypothesis was that the layers would act as barriers to prevent hazards from causing losses. To test the model, a dataset (secondary data) of food safety assessments from 1,536 different restaurant establishments in Brazil was used. A checklist of 51 items was organised into seven layers of defence system. The model was tested with a Partial Least Square Structural Equation Model. Errors in administrative controls (facilities and training) led to errors in behavioural controls. A 'cascade effect' was observed where errors in distal behavioural controls (safe ingredients and water and environmental hygiene) impacted proximal controls (personal and food hygiene and; safe food temperature) and system controls. It was discussed how latent conditions and active failures can string together and cause a foodborne illness incident. The Swiss Cheese Model of food safety incidents is proposed as a new perspective for food safety. This model can be used for risk management and food safety education.

O presente artigo tem como objetivo analisar a inadmissibilidade de provas ilícitas, que está prevista no artigo 5°, LVI, da Constituição do Brasil de 1988, sendo uma garantia fundamental do cidadão contra abusos do Estado. Como admitir a utilização de provas ilícitas para se comprovar a suspeição do Magistrado, uma vez que na relação processual, é presentante do Estado. Portanto, não se está diante de um conflito de direitos fundamentais envolvendo duas pessoas, mas sim um réu e o Poder Judiciário, que deve ser o garantidor do devido processo legal substancial. O método da pesquisa é o dedutivo.

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.

Contains fulltext : 253358.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 253358.pdf (Publisher’s version ) (Open Access)

Neurodevelopmental disorders are highly heterogenous conditions resulting from abnormalities of brain architecture and/or function. FBXW7 (F-box and WD-repeat-domain-containing 7), a recognized developmental regulator and tumor suppressor, has been shown to regulate cell-cycle progression and cell growth and survival by targeting substrates including CYCLIN E1/2 and NOTCH for degradation via the ubiquitin proteasome system. We used a genotype-first approach and global data-sharing platforms to identify 35 individuals harboring de novo and inherited FBXW7 germline monoallelic chromosomal deletions and nonsense, frameshift, splice-site, and missense variants associated with a neurodevelopmental syndrome. The FBXW7 neurodevelopmental syndrome is distinguished by global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues. Brain imaging detailed variable underlying structural abnormalities affecting the cerebellum, corpus collosum, and white matter. A crystal-structure model of FBXW7 predicted that missense variants were clustered at the substrate-binding surface of the WD40 domain and that these might reduce FBXW7 substrate binding affinity. Expression of recombinant FBXW7 missense variants in cultured cells demonstrated impaired CYCLIN E1 and CYCLIN E2 turnover. Pan-neuronal knockdown of the Drosophila ortholog, archipelago, impaired learning and neuronal function. Collectively, the data presented herein provide compelling evidence of an F-Box protein-related, phenotypically variable neurodevelopmental disorder associated with monoallelic variants in FBXW7.

PURPOSE: Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP. METHODS: Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay. RESULTS: The phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants. CONCLUSION: NEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing.

Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression, and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using machine learning classifiers trained to distinguish disease-associated from dispensable genes, we classify 247 genes, including 115 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.

O presente artigo tem como objetivo analisar a inadmissibilidade de provas ilícitas, que está prevista no artigo 5°, LVI, da Constituição do Brasil de 1988, sendo uma garantia fundamental do cidadão contra abusos do Estado. Como admitir a utilização de provas ilícitas para se comprovar a suspeição do Magistrado, uma vez que na relação processual, é presentante do Estado. Portanto, não se está diante de um conflito de direitos fundamentais envolvendo duas pessoas, mas sim um réu e o Poder Judiciário, que deve ser o garantidor do devido processo legal substancial. O método da pesquisa é o dedutivo.

O presente artigo tem como objetivo analisar a inadmissibilidade de provas ilícitas, que está prevista no artigo 5°, LVI, da Constituição do Brasil de 1988, sendo uma garantia fundamental do cidadão contra abusos do Estado. Como admitir a utilização de provas ilícitas para se comprovar a suspeição do Magistrado, uma vez que na relação processual, é presentante do Estado. Portanto, não se está diante de um conflito de direitos fundamentais envolvendo duas pessoas, mas sim um réu e o Poder Judiciário, que deve ser o garantidor do devido processo legal substancial. O método da pesquisa é o dedutivo.

Purpose: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations. Methods: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases. All missense variants were mapped onto the 3-dimensional structure of the GABRB3 subunit, and clinical phenotypes associated with the different key structural domains were investigated. Results: We characterized 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 12 months, and mild-to-moderate ID were associated with variants in the extracellular domain. Focal epilepsy with earlier onset (median: age 4 months) and severe ID were associated with variants in both the pore-lining helical transmembrane domain and the extracellular domain. Conclusion: These genotype-phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Alternative splicing (AS) is crucial for cell-type-specific gene transcription and plays a critical role in neuronal differentiation and synaptic plasticity. De novo frameshift variants in NOVA2, encoding a neuron-specific key splicing factor, have been recently associated with a new neurodevelopmental disorder (NDD) with hypotonia, neurological features, and brain abnormalities. We investigated eight unrelated individuals by exome sequencing (ES) and identified seven novel pathogenic NOVA2 variants, including two with a novel localization at the KH1 and KH3 domains. In addition to a severe NDD phenotype, novel clinical features included psychomotor regression, attention deficit-hyperactivity disorder (ADHD), dyspraxia, and urogenital and endocrinological manifestations. To test the effect of the variants on splicing regulation, we transfected HeLa cells with wildtype and mutant NOVA2 complementary DNA (cDNA). The novel variants NM_002516.4:c.754_756delCTGinsTT p.(Leu252Phefs*144) and c.1329dup p.(Lys444Glnfs*82) all negatively affected AS events. The distal p.(Lys444Glnfs*82) variant, causing a partial removal of the KH3 domain, had a milder functional effect leading to an intermediate phenotype. Our findings expand the molecular and phenotypic spectrum of NOVA2-related NDD, supporting the pathogenic role of AS disruption by truncating variants and suggesting that this is a heterogeneous condition with variable clinical course.

This study aims to discuss the use of multiple layers of defence to prevent foodborne illness in restaurants. A defence model was developed based on Reason’s Swiss Cheese Model. Reason’s model was extended by adding the concept of Hazard Analysis and Critical Control Points, as well as Five Keys to Safer Food. The defence system was divided into seven layers of defence: 1) adequate facilities and 2) training as administrative controls; 3) safe ingredients and water; 4) environmental hygiene; 5) personal and food hygiene and 6) safe food temperature as behavioural controls; and 7) control and systems. The hypothesis was that the layers would act as barriers to prevent hazards from causing losses. To test the model, a dataset (secondary data) of food safety assessments from 1,536 different restaurant establishments in Brazil was used. A checklist of 51 items was organised into seven layers of defence system. The model was tested with a Partial Least Square Structural Equation Model. Errors in administrative controls (facilities and training) led to errors in behavioural controls. A 'cascade effect' was observed where errors in distal behavioural controls (safe ingredients and water and environmental hygiene) impacted proximal controls (personal and food hygiene and; safe food temperature) and system controls. It was discussed how latent conditions and active failures can string together and cause a foodborne illness incident. The Swiss Cheese Model of food safety incidents is proposed as a new perspective for food safety. This model can be used for risk management and food safety education.

Alternative splicing (AS) is crucial for cell-type-specific gene transcription and plays a critical role in neuronal differentiation and synaptic plasticity. De novo frameshift variants in NOVA2, encoding a neuron-specific key splicing factor, have been recently associated with a new neurodevelopmental disorder (NDD) with hypotonia, neurological features, and brain abnormalities. We investigated eight unrelated individuals by exome sequencing (ES) and identified seven novel pathogenic NOVA2 variants, including two with a novel localization at the KH1 and KH3 domains. In addition to a severe NDD phenotype, novel clinical features included psychomotor regression, attention deficit-hyperactivity disorder (ADHD), dyspraxia, and urogenital and endocrinological manifestations. To test the effect of the variants on splicing regulation, we transfected HeLa cells with wildtype and mutant NOVA2 complementary DNA (cDNA). The novel variants NM_002516.4:c.754_756delCTGinsTT p.(Leu252Phefs*144) and c.1329dup p.(Lys444Glnfs*82) all negatively affected AS events. The distal p.(Lys444Glnfs*82) variant, causing a partial removal of the KH3 domain, had a milder functional effect leading to an intermediate phenotype. Our findings expand the molecular and phenotypic spectrum of NOVA2-related NDD, supporting the pathogenic role of AS disruption by truncating variants and suggesting that this is a heterogeneous condition with variable clinical course.

SLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of clinical features of patients with SLITRK2 variants. Furthermore, impaired excitatory synapse maintenance induced by hippocampal CA1-specific cKO of Slitrk2 caused abnormalities in spatial reference memory. Collectively, these data suggest that SLITRK2 is involved in X-linked neurodevelopmental disorders that are caused by perturbation of diverse facets of SLITRK2 function.

Large wood (LW) accumulations can cause several damages, especially if the recruited wood is transported during floods down to urban areas, like Lourdes (France). One of the most serious problems concerning bridges and weirs all around the world is the formation of LW accumulations, that might be responsible for the structure’s failure. However, the transport and deposition of LW during floods are very complex processes, which make predictions of these accumulations’ locations and potential impacts very challenging. Thus, reducing the LW-related risks is difficult. Thereby, we are conducting a study to assess the LW-related hazards by applying a numerical model of the Gave-de-Pau River. The software called Iber-Wood is a hydrodynamic model based on the 2D Saint Venant equations coupled to a wood dynamics module that simulates wood transport explicitly. It allows analyzing the LW accumulations’ formation, depending on several input parameters. The aim of this study was to simulate wood transport during floods, in order to identify the potential risks created by the formation of LW accumulations in Lourdes’ city center. The paper first proposes a framework to calibrate the parameters of LW-supply (flux and size of logs) based on the typical dataset available in France. It then presents a preliminary study of the 2D hydrodynamic model showing its potential to identify preferential storage areas and bridges prone to the formation of LW accumulations. The calibration phase of the model is not finished yet, but we can highlight some recommendations on LW-transport modelling from these early stage results., The study was performed within the scope of the Research Project 2015/19/N/ST10/01526 financed by the National Science Centre of Poland., Postprint (published version)

This study aims to discuss the use of multiple layers of defence to prevent foodborne illness in restaurants. A defence model was developed based on Reason’s Swiss Cheese Model. Reason’s model was extended by adding the concept of Hazard Analysis and Critical Control Points, as well as Five Keys to Safer Food. The defence system was divided into seven layers of defence: 1) adequate facilities and 2) training as administrative controls; 3) safe ingredients and water; 4) environmental hygiene; 5) personal and food hygiene and 6) safe food temperature as behavioural controls; and 7) control and systems. The hypothesis was that the layers would act as barriers to prevent hazards from causing losses. To test the model, a dataset (secondary data) of food safety assessments from 1,536 different restaurant establishments in Brazil was used. A checklist of 51 items was organised into seven layers of defence system. The model was tested with a Partial Least Square Structural Equation Model. Errors in administrative controls (facilities and training) led to errors in behavioural controls. A 'cascade effect' was observed where errors in distal behavioural controls (safe ingredients and water and environmental hygiene) impacted proximal controls (personal and food hygiene and; safe food temperature) and system controls. It was discussed how latent conditions and active failures can string together and cause a foodborne illness incident. The Swiss Cheese Model of food safety incidents is proposed as a new perspective for food safety. This model can be used for risk management and food safety education.

In various international reports studying employment across countries and over time (see for example OECD or IMF reports), some groups are systematically highlighted as more vulnerable or less present in the labour market. This is the case of the youths, older people, women, people with a foreign origin and those with a low level of education. The aim of this thesis is to better understand the main driving forces explaining the labour market situation of those vulnerable groups, with a special attention devoted to people with a foreign origin (Chapter 2 and Chapter 3) and women (Chapter 4). Both institutional settings and personal characteristics are deeply analysed.Using data from European countries, Chapter 1 provides robust estimates on how product and labour market regulation could influence the unemployment rate. Controlling for country fixed effects, endogeneity, and a large set of covariates, results show that product market deregulation overall reduces the unemployment rate. This finding is robust across all specifications and in line with theoretical predictions. However, not all types of product market reforms have the same effect: deregulation of state controls and in particular involvement in business operations tend to push up the unemployment rate, while barriers to entrepreneurship and barriers to trade tend to reduce it. Regarding labour market deregulation, our estimations show an increase in the unemployment rate in the short run, while a positive impact (i.e. a reduction in the unemployment rate) occurs only in the long run. Analysis by sub-indicators shows that reducing protection against collective dismissals helps in reducing the unemployment rate. This Chapter also analyses how unemployment’s effects of deregulations could vary depending on the type of workers. Although men and women are equally affected by product and labour market deregulations, workers distinguished by age and educational attainment are affected differently. In terms of emp, Dans divers rapports internationaux étudiant l'emploi dans les pays et dans le temps (voir par exemple les rapports de l'OCDE ou du FMI), certains groupes sont systématiquement mis en évidence comme étant plus vulnérables ou moins présents sur le marché du travail. C'est le cas des jeunes, des personnes âgées, des femmes, des personnes d'origine étrangère et des personnes ayant un faible niveau d'éducation. L'objectif de cette thèse est de mieux comprendre les principales forces motrices qui expliquent la situation de ces groupes vulnérables sur le marché du travail, en accordant une attention particulière aux personnes d'origine étrangère (chapitre 2 et chapitre 3) et aux femmes (chapitre 4). Les contextes institutionnels et les caractéristiques personnelles sont analysés en profondeur.En utilisant des données provenant de pays européens, le chapitre 1 fournit des estimations robustes sur la manière dont la réglementation des marchés de produits et du travail pourrait influencer le taux de chômage. En contrôlant les effets fixes du pays, l'endogénéité et un large ensemble de covariables, les résultats montrent que la déréglementation du marché des produits réduit globalement le taux de chômage. Cette conclusion est robuste dans toutes les spécifications et conforme aux prédictions théoriques. Cependant, tous les types de réformes des marchés de produits n'ont pas le même effet :la déréglementation des contrôles de l'État et en particulier l'implication dans les opérations commerciales tendent à faire augmenter le taux de chômage, tandis que les obstacles à l'esprit d'entreprise et les obstacles au commerce tendent à le réduire. En ce qui concerne la déréglementation du marché du travail, nos estimations montrent une augmentation du taux de chômage à court terme, tandis qu'un impact positif (c'est-à-dire une réduction du taux de chômage) ne se produit qu'à long terme. L'analyse par sous-indicateurs montre que la réduction de la protection contre les licenciements co, Doctorat en Sciences économiques et de gestion, info:eu-repo/semantics/nonPublished

OBJECTIVE: Asparagine-linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis. METHODS: We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants. RESULTS: The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one-half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one-third of all cases paroxysms of fast activity with electrodecrement. ALG13-related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one-third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired. SIGNIFICANCE: X-linked ALG13-related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.

We study the daily to interannual variability of the Red River plume in the Gulf of Tonkin from numerical simulations at high resolution over 6 years (2011–2016). Compared with observational data, the model results show good performance. To identify the plume, passive tracers are used in order to (1) help distinguish the freshwater coming from different continental sources, including the Red River branches, and (2) avoid the low salinity effect due to precipitation. We first consider the buoyant plume formed by the Red River waters and three other nearby rivers along the Vietnamese coast. We show that the temporal evolution of the surface coverage of the plume is correlated with the runoff (within a lag), but that the runoff only cannot explain the variability of the river plume; other processes, such as winds and tides, are involved. Using a K-means unsupervised machine learning algorithm, the main patterns of the plume and their evolution in time are analyzed and linked to different environmental conditions. In winter, the plume is narrow and sticks along the coast most of the time due to the downcoast current and northeasterly wind. In early summer, the southwesterly monsoon wind makes the plume flow offshore. The plume reaches its highest coverage in September after the peak of runoff. Vertically, the plume thickness also shows seasonal variations. In winter, the plume is narrow and mixed over the whole water depth, while in summer, the plume can be detached both from the bottom and the coast. The plume can deepen offshore in summer, due to strong wind (in May, June) or specifically to a recurrent eddy occurring near 19°N (in August). This first analysis of the variability of the Red River plume can be used to provide a general picture of the transport of materials from the river to the ocean, for example in case of anthropogenic chemical substances leaked to the river. For this purpose, we provide maps of the receiving basins for the different river systems in

We study the daily to interannual variability of the Red River plume in the Gulf of Tonkin from numerical simulations at high resolution over 6 years (2011–2016). Compared with observational data, the model results show good performance. To identify the plume, passive tracers are used in order to (1) help distinguish the freshwater coming from different continental sources, including the Red River branches, and (2) avoid the low salinity effect due to precipitation. We first consider the buoyant plume formed by the Red River waters and three other nearby rivers along the Vietnamese coast. We show that the temporal evolution of the surface coverage of the plume is correlated with the runoff (within a lag), but that the runoff only cannot explain the variability of the river plume; other processes, such as winds and tides, are involved. Using a K-means unsupervised machine learning algorithm, the main patterns of the plume and their evolution in time are analyzed and linked to different environmental conditions. In winter, the plume is narrow and sticks along the coast most of the time due to the downcoast current and northeasterly wind. In early summer, the southwesterly monsoon wind makes the plume flow offshore. The plume reaches its highest coverage in September after the peak of runoff. Vertically, the plume thickness also shows seasonal variations. In winter, the plume is narrow and mixed over the whole water depth, while in summer, the plume can be detached both from the bottom and the coast. The plume can deepen offshore in summer, due to strong wind (in May, June) or specifically to a recurrent eddy occurring near 19°N (in August). This first analysis of the variability of the Red River plume can be used to provide a general picture of the transport of materials from the river to the ocean, for example in case of anthropogenic chemical substances leaked to the river. For this purpose, we provide maps of the receiving basins for the different river systems in