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Advances in breast cancer treatment have markedly reduced the incidence of massive bleeding, yet severe hemorrhage remains a critical issue in locally advanced or metastatic cases. Traditional management strategies often prove inadequate for significant bleeding, highlighting the need for alternative interventions. We detail the management of a 64-year-old patient with a neglected locally advanced breast tumor, leading to life-threatening hemorrhage. Conventional bleeding control measures failed, necessitating microsphere embolization. Effective hemostasis was achieved without adverse events or recurrence of bleeding, allowing for the initiation of chemotherapy. This case underscores the rarity yet potential severity of hemorrhage in breast cancer, challenging conventional management. Embolization, typically reserved for other hemorrhagic conditions, is appearing as a viable alternative for breast cancer-related hemorrhage, particularly in large tumors where surgery is impractical. Further research is necessary to establish its role in managing minor bleeding.

ABSTRACT: Mastitis is one of the most common diseases of dairy cattle. It has a high impact on-farm economy, farmers' working time, and antimicrobial usage (AMU). Selective dry cow therapy (SDCT) is an effective means of reducing AMU without negatively affecting udder health. The objective of our study was to evaluate the impact of SDCT implementation on farmer income, working time, and AMU, using a bioeconomic model. A stochastic dairy simulation model (DairyHealthSim) based on a weekly model was used to simulate herd dynamics, reproduction, milk production, culling decisions, health outcomes, and the management of health events. A specific module was developed for the simulation of quarter-level IMI acquisition and elimination during the lactation and dry-off periods, and 25 different farm settings were defined to represent herds with various udder health situations. We then defined 20 scenarios of SDCT by combining both the use of different thresholds of SCC and milk bacteriology for treatment allocation and the use of internal teat sealant (ITS). All SDCT protocols had little effect on farmer income, and we identified some protocols with a positive farm gross margin (up to Can$15.83/dried cow; at time of writing, Can$1 = US$0.72). We also found that adding an ITS to all cows led to greater economic gain. The application of SDCT had little effect on farmers' working time, except when milk bacteriology was used for decision making. Antimicrobial treatment to all cows above 200,000 cells/mL at last control, with the use of ITS on all cows, seems a good choice in most dairy farms. These findings could be used to convince farmers to adopt this strategy at dry-off.

Abstract Personality is a central concept and a cross-domain explanatory factor in psychology to characterize and differentiate individuals. Surprisingly, among the many studies on oculomotor behavior, only a few have investigated how personality influences the exploration of a visual stimulus. Due to the limited number of existing studies, it is still uncertain if markers of personality in eye movements are always observable in eye movements across various exploration contexts. Here, introducing a novel concept of gaze-based signatures of personality, we used visual exploration metrics to detect personality signatures across various exploration contexts (visual search and free-viewing on images and webpages) in 91 participants. Personality data were collected as in the reference paper that validated the French version of the Big Five Inventory. Linear regression analyses demonstrated that while Extraversion and Openness to Experience did not correlate with any particular exploration metric, the other three traits–Conscientiousness, Agreeableness, and Neuroticism–correlated robustly with all exploration metrics in different visual exploration contexts. Our study provides evidence for the capture of the gaze-based signature of personality from very brief eye movement recordings.

Abstract Background Varicocele embolization is an effective, minimally invasive treatment option, with a symptom improvement rate of around 90%. However, anatomical variations and post-embolization recurrences pose challenges to its efficacy. This article discusses the antegrade embolization technique as a viable alternative for cases in which retrograde embolization fails, offering a broader spectrum of treatment options for varicocele. Case presentation This case report details the treatment of a 27-year-old male with a left varicocele, diagnosed during infertility assessment, using an alternative embolization technique. Despite initial failed attempts at retrograde catheterization via the femoral vein, a direct inguinal puncture of the left testicular vein was successfully performed under ultrasound guidance. A mixture of Glubran® and Lipiodol® was used for embolization, achieving varicocele embolization without complications. The patient was discharged 2 hours post-procedure, with follow-up confirming the procedure’s effectiveness and safety. Conclusion This article introduces a less invasive, ultrasound-guided technique for varicocele embolization, presenting a viable alternative to surgery when conventional retrograde methods fail. Graphical Abstract

Abstract Quantitative measurement of light intensity is a key step in ensuring the reliability and the reproducibility of scientific results in many fields of physics, biology, and chemistry. The protocols presented so far use various photoactive properties of manufactured materials. Here, leaves are introduced as an easily accessible green material to calibrate light intensity. The measurement protocol consists in monitoring the chlorophyll fluorescence of a leaf while it is exposed to a jump of constant light. The inverse of the characteristic time of the initial chlorophyll fluorescence rise is shown to be proportional to the light intensity received by the leaf over a wide range of wavelengths and intensities. Moreover, the proportionality factor is stable across a wide collection of plant species, which makes the measurement protocol accessible to users without prior calibration. This favorable feature is finally harnessed to calibrate a source of white light from exploiting simple leaves collected from a garden.

Characterizing seeds of tropical weeds is crucial for future research to understand their ability to disperse in space and time through their seeds, and building up seed banks. Seeds of 55 weed species occurring on Reunion Island were collected and characterized. Seeds were described by their shape, size, color, texture, hairiness, or particular markings. Seed traits were recorded in a database in French and English. It has been published on the CIRAD AMATROP dataverse, which centralizes datasets on tropical weeds. It will be updated as new weed seeds from tropical regions are characterized. In a long-term perspective, these data allow for creating a multicriteria identification key to identify seeds to study seed stocks in agricultural fields.

Abstract Light pollution, by changing organisms’ behavior, affects locomotion, migration and can ultimately fragment the habitat. To investigate the effects of light pollution on habitat fragmentation, we conducted an experimental study on a nocturnal and photosensitive primate, the grey mouse lemur (Microcebus murinus). Twelve males were housed individually in an apparatus with two cages connected by two corridors, opaque and transparent. During 4 nights, the transparent corridor was illuminated by specific light intensities: 0 lx, 0.3 lx, 20 lx and 51.5 lx corresponding respectively to total darkness, full moon, minimal intensity recommended by the European standard EN-13201 on public lighting, and to light pollution recorded in an urban area. Each night, general activity, use of corridors and cage occupancy were recorded using an infrared camera. For the first time in a nocturnal primate, results demonstrate that light pollution changes the preference of use of corridors, modifies the locomotor pattern and limits the ability of animals to efficiently exploit their environment according to a light intensity-dependent relationship. However, results indicate that a dark corridor allows partial compensation partly preserving general activities. This study highlights the necessity to consider light pollution during the implementation of conservation plans and the relevance of nocturnal frames.

Les prairies et pâturages représentent 25 % des terres émergées. Une exploitation efficiente et durable de ces ressources fourragères nécessite notamment une gestion adaptée des plantes envahissantes très souvent responsables de leur dégradation. Cette gestion nécessite de disposer de connaissances sur leur comportement et pour cela une bonne identification. Le portail collaboratif Wiktrop aide à identifier les adventices et facilite le partage et la diffusion des connaissances sur les adventices tropicales et leur gestion entre acteurs de terrain et scientifiques. Ces connaissances permettent d’améliorer les pratiques de contrôle des adventices dans l’ensemble des régions tropicales et méditerranéennes. La contribution des utilisateurs est un facteur important de la qualité et de l’étendue des informations mises à disposition. Ce portail évoluera prochainement avec l’intégration des plantes fourragères et des plantes de services tropicales.

Understanding patterns in coral reproductive biology at local and regional scales is crucial to elucidate our knowledge of characteristics that regulate populations and communities. The lack of published data on coral spawning patterns in the Maldives hinders our understanding of coral reproductive biology and limits our ability to assess shifts in reproductive phenology over time. Here we document baseline environmental cues, spawning patterns, exact timings and oocyte development of restored and wild Acropora, inhabiting shallow water reefs, across two Maldivian atolls. A total of 1,200 colonies were recorded spawning across the two sites between October 2021 and April 2023. These colonies represent 22 species of Acropora, with coral spawning observed over an extended period of eight months. This research details exact spawning times of multi-specific spawning, asynchronous spawning and ‘split spawning’ of Acropora, across multiple lunar phases; and highlights the need to consider restored colonies when discussing the sexual reproductive patterns of Maldivian Acropora in the future. Overall, corals spawned earlier in North Male Atoll compared with Baa Atoll. Earlier spawning events were significantly correlated with lower tide depths, wind speeds, daily precipitation and higher sea surface temperatures which helped explain inter-atoll, inter-annual, and intra-annual variations in spawning day. This study contributes to understanding sexual reproductive cycles of Acropora in the Maldives; knowledge that is vital for effective management of a critically endangered ecosystem in a changing climate.

BackgroundIntensity-modulated conformal radiotherapy (IMRT) has become the technique of choice for the treatment of locally advanced or inoperable non-small cell lung cancer (NSCLC). Nevertheless, this technique presents dosimetric uncertainties, particularly in treating moving targets such as pulmonary neoplasms. Moreover, it theoretically increases the risk of isolated nodal failure (INF) due to reduced incidental irradiation.ObjectiveThe objective of this study was to evaluate the efficacy and safety of IMRT in patients with inoperable NSCLC and to describe the pattern of relapses.MethodsPatients with locally advanced NSCLC treated with radiotherapy and chemotherapy between 2015 and 2018 at the Oscar Lambret Center were retrospectively included in the study. Overall and progression-free survival were estimated using the Kaplan–Meier method. The cumulative incidence of the different components of relapse was estimated using the Kalbfleisch and Prentice method. Prognostic factors for relapse/death were investigated using the Cox model. A comparison with literature data was performed using a one-sample log-rank test.ResultsSeventy patients were included, and 65 patients (93%) had stage III disease. All the patients received chemotherapy, most frequently with cisplatin and navelbine. The dose received was 66 Gy administered in 33 fractions. The median follow-up and survival were 49.1 and 39.1 months, respectively. A total of 35 deaths and 43 relapses, including 29 with metastatic components, were reported. The overall survival rates at 1 and 2 years were 80.2% (95% confidence interval 68.3%-88.0%) and 67.2% (95% confidence interval 54.2%-77.3%), respectively. Locoregional relapse was observed in 14 patients, including two INF, one of which was located in the lymph node area adjacent to the clinical target volume. Median relapse-free survival was 15.2 months. No variable was statistically associated with the risk of relapse/death in multivariate analysis. Seven patients (10%) experienced grade 3 or higher toxicity.ConclusionThe use of IMRT for locally advanced or inoperable NSCLC led to favorable long-term clinical outcomes. The rate of locoregional relapse, particularly isolated lymph node failure, was low and comparable with that of the three-dimensional radiotherapy series, as was the rate of early and late toxicities.

Abstract This paper presents the development of a tool to perform risk assessment for deep geothermal projects. The tool is aimed at project developers to help them present their project to local authority, decision-makers and financers so they can highlight how they take into account risks and consider mitigation measures to minimize them. The main criteria for this tool are the simplicity of use, the quality of presentation and flexibility. It is based on results from the H2020 GEORISK project that identified risks that apply to geothermal projects and proposed insurance schemes all over Europe. A characteristic of this tool is that it considers all the categories of risks that a project may face, including geological, technical, environmental risks as well as risks related to the social, economic and political contexts. The tool can be customized: selection of risks in a list that can be completed, adaptable rating scheme for risk analysis, possibility to choose the best display for results depending on the user needs. Two case applications are presented, one in the Paris Basin considering a doublet targeting the Upper Trias, a geological layer that presents some technical challenges; and one in the Upper Rhine graben targeting a fault zone, where the risk of induced seismicity must be carefully considered. A posteriori risk assessment highlights the main issues with these types of projects, and the comparison between the two cases emphasizes the flexibility of the tool, as well as, the different ways to present the results depending on the objective of the analyses.

A togatus, dating to the first part of the 1st c. AD, was discovered, in proximity to a Roman road, during the archaeological survey of an urban district of Briord (Ain).This discovery sheds new light on the Roman centre of Briord, located between Lyon and Geneve, on the right bank of the river Rhône, and at the border of Vienne and the Allobroges civitas. Briord was not a well-known city, but the recent archaeological efforts revealed an important throughway functioning in Antiquity (1st-3rd c. AD) and early outlines of other routes, as well as an important necropolis in the north, and a bathhouse (2nd c. AD). An inscription provides us with the name of the village: Brioratis, [Br]ioratenses (CIL XIII, 2464 ; ILAin, 2005, 28). Unfortunately, the information provided is not precise enough to draft a map of the township in Antiquity, but generally speaking, it appears to correspond well to an overlay of the modern plan of the church’s perimeter. The major public buildings have yet to be discovered, but some large substructures had been located near the church. A cult of Mercury is attested to by the discovery of a bronze statuette, an altar (CIL XIII, 2461 ; ILAin 2005, 24) and a gift of a proscaenium to the god (CIL XIII, 2462 ; ILAin 2005, 25).The Roman road that crosses Briord measures eight metres in width and was used since the beginning of the 1st c. to the end of the 3rd c. AD. The preliminary excavation focused on an urban district named “rue Saint-Didier, Les Ecolus”. The trench where the statue was discovered was located along the edge of the road. This layer was composed of a deep layer of coal dust mixed with scraps of metal and ceramics (dated to 27 BC-60 AD) and which was covered by a thick layer of a backfill. The latter was comprised of vestiges belonging to demolition phases, including the statue, some large limestone blocks and other, smaller fragments of lime. The second excavation, performed in 2020 provided us with further architectural clues regarding a funerary monument (E. Polo, unpublished).The sculpted limestone object is nearly complete and represents a local product for which three possible quarries, located close to Briord, may be considered as sources for the material. The sculpture had been carved in a single block. A small piece of the right arm, the end of the legs and the feet are missing. The back of the sculpture is unfinished. Small fractures damage the nose, the left cheek and the chin.The subject depicted by the sculpture is that of a young man, a private citizen, wearing a toga. His face is oval and regular, and is not lined by wrinkles. His short hairstyle corresponds to the fashion of the Julio-Claudian period. The short fringe is paired with small and even locks, which are arranged similarly to hairstyles visible in some portraits of Tiberius and Caligula, during the reign of Tiberius to that of Claudius.The toga depicted by the sculpture presents a number of noteworthy characteristics, including: the hanging strip of cloth, formed by the material flowing from the left shoulder to the right hand. The figure appears to have a pronounced swaying of the hips and there is some corresponding twisting of the pleats below the left hand. This toga, without umbo, retains, in its overall shape, certain features of the Roman toga dating to the 1st c. BC. The separate swathe of cloth held by the right hand of the sculpted individual, however, represents a rare feature. A Julio-Claudian togatus discovered in Barcino is a close comparison. Indeed, the Roman toga of Briord is halfway between the new trends of its period and the old Italic influences. New research into the beginning of the 1st c. AD, will provide insight into toga trends of the Early Roman Empire.This local sculpture, likely belonging to a funerary monument, is now a major piece by virtue of its unique feature and fine quality in the study of the sculpture in Gaul during the Tiberius-Claudius period.

Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disorder that can result in significant morbidity and mortality. This report details an iatrogenic aortic rupture during an endovascular approach in the management of critical limb ischemia in a 27-year-old woman who presented with acute onset of severe sensory deficit of the left leg. Conversion to open repair with a midline laparotomy and an aortic-left popliteal bypass was performed. In the endovascular era, we highlight that even minimally invasive therapeutic interventions can have devastating adverse events in patients with vascular Ehlers-Danlos syndrome.

Abstract Background Pancreatic microcystic serous cystadenoma are rare benign pancreatic tumors. No treatment is needed in most cases as this lesion is often discovered incidentally. Surgery is not required except in symptomatic cases. Case presentation We report herein a rare case of pancreatic serous cystadenoma complicated with a hemorrhage in a 95 years old patient treated with arterial embolization since surgery was not possible. The patient recovered without any adverse events or bleed recurrence in the 6 months following the procedure. Conclusion Hemorrhage secondary to a pancreatic serous cystadenoma was successfully treated with arterial embolization, which may represent an alternative therapeutic option to surgery.

This article proposes a systematic review of the recent literature on the impacts of the deployment of autonomous vehicles through the lens of lifestyle changes that will modify our mobility practices. It discusses the main findings of the studies, analyzes their links with the foresight methods used by their authors, and identifies research gaps. Four components of lifestyles are considered: residential location, car ownership, activity patterns, and tourism. Particular attention is given to the diversity of the reviewed foresight approaches, to the way they complement one another in the construction of knowledge, and to their influence on the forecasts and the lessons learned. Our work shows a convergence of results across methods, especially for expected impacts on household location and car ownership, and the influence of the way autonomous vehicles are deployed. Our analysis also makes it possible to draw up a more comprehensive and nuanced picture of the anticipated changes in lifestyles, and the main sources of uncertainty. Finally, our work identifies several research gaps and avenues for future studies such as the impacts on job choices and tourism, the need for a better understanding of the links between the different deployment models for autonomous vehicles, and the need to explore more scenarios that are compatible with environmentally- and socially-oriented goals.

Mental workload (MWL) is a concept that is used as a reference for assessing the mental cost of activities. In recent times, challenges related to user experience are determining the expected MWL value for a given activity and real-time adaptation of task complexity level to achieve or maintain desired MWL. As a consequence, it is important to have at least one task that can reliably predict the MWL level associated with a given complexity level. In this study, we used several cognitive tasks to meet this need, including the N-Back task, the commonly used reference test in the MWL literature, and the Corsi test. Tasks were adapted to generate different MWL classes measured via NASA-TLX and Workload Profile questionnaires. Our first objective was to identify which tasks had the most distinct MWL classes based on combined statistical methods. Our results indicated that the Corsi test satisfied our first objective, obtaining three distinct MWL classes associated with three complexity levels offering therefore a reliable model (about 80% accuracy) to predicted MWL classes. Our second objective was to achieve or maintain the desired MWL, which entailed the use of an algorithm to adapt the MWL class based on an accurate prediction model. This model needed to be based on an objective and real-time indicator of MWL. For this purpose, we identified different performance criteria for each task. The classification models obtained indicated that only the Corsi test would be a good candidate for this aim (more than 50% accuracy compared to a chance level of 33%) but performances were not sufficient to consider identifying and adapting the MWL class online with sufficient accuracy during a task. Thus, performance indicators require to be complemented by other types of measures like physiological ones. Our study also highlights the limitations of the N-back task in favor of the Corsi test which turned out to be the best candidate to model and predict the MWL among several cognitive tasks.

Dual photo- and metal-catalysis is generally not well-understood when the metal catalyst is a gold complex. Here the authors show that a variation of a known metallaphotoredox annulation is possible without an added photocatalyst, proceeding putatively through a gold–intermediate photosensitization by the aggregate of a potassium amide reactant, and yielding indole derivatives.

Label discrimination is challenging in fluorescence microscopy due to broad spectra and narrow lifetime distribution. Here, the authors introduce extra kinetic dimensions by illuminating reversibly photoswitchable fluorophores with different intensities, and discriminate 20 spectrally similar fluorophores.

Background: Sarcoidosis is a multisystem granulomatous disease with a wide variety of presentations and clinical courses. Cutaneous manifestations and comorbidities associated with sarcoid prognosis remain understudied. Methods: An EPIC query was run for patients age 18+ at the Johns Hopkins Hospital with a diagnosis of sarcoidosis of the skin according to the ICD-10-CM code D86.3. Data were obtained from a population-based sample of 240 patients from 2015 to 2020. Results: A total of 240 patients were included in the cohort study. The mean (SD) age was 43.76 (11.72) years, and 30% of participants were male; 76.25% of patients identified as black, 19.58% as white, and 4.17% as other. The average age of onset in remissive patients was significantly higher than progressive (47 ± 12 vs. 40 ± 10, p = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (p = 0.028). Progressive disease was associated with the presence of lupus pernio (aOR = 3.29, 95% CI, 1.60–6.77) and at least one autoimmune comorbidity (aOR 6.831, 95% CI 1.819–11.843). Conclusions: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis.

Fluorescent reporters spanning the visible spectrum are needed for imaging live cells and organisms. Here the authors report a collection of fluorogenic chromophores that cover the visible spectrum from blue to red using a single engineered and optimised protein tag.

The influence of the bonding procedure (the adhesive type, application procedure, etc.) on the static and dynamic strain transfers of bonded optical fibre sensors is studied theoretically and experimentally at room temperature. The achievable performances with four different types of adhesives (three urethane and one epoxy adhesive), and with different fibre types, are evaluated: acrylate-coated, polyimide-coated, and bare single-mode optical fibres. Static strain measurements, ranging from 20 to 200 µ strain, are performed using both fibre Bragg gratings (FBGs) and optical frequency domain reflectometry (OFDR), and are compared to reference strain-gauge measurements, and to the proposed analytical model, which is developed on the basis of stress equilibrium relations. This model is valid for bonding to all types of linear and elastic materials, as long as there is no sliding between the host material, the adhesive, and the optical fibre. The results agree between the analytical model and the experiments. Regarding the dynamic sinusoidal strain measurements, the studied dynamic range is from 10 to 100 Hz, and only the FBGs are tested. The results demonstrate that the sensitivities of strain sensors based on bonded uncoated fibres or bonded polyimide-coated fibres are comparable to those of strain gauges, and that it is possible to use bonded FBGs for precise dynamic strain measurements.

ABSTRACT Methylothon is an inquiry-based high school learning module in microbial ecology, molecular biology, and bioinformatics that centers around pink-pigmented plant-associated methylotrophic bacteria. Here, we present an overview of the module’s learning goals, describe course resources (available for public use at http://methylothon.com), and relate lessons learned from adapting Methylothon for remote learning during the pandemic in spring of 2021. This curriculum description is intended not only for instructors but also for microbial ecology researchers with an interest in conducting K-12 outreach. The original in-person version of the module allows students to isolate their own strains of methylotrophic bacteria from plants they sample from the environment, to identify these using PCR, sequencing, and phylogenetic analysis, and to contribute their strains to original research in a university lab. The adapted version strengthens the focus on bioinformatics and increases its flexibility and accessibility by making the lab portion optional and adopting free web-based tools. Student feedback and graded assignments from spring 2021 revealed that the lesson was especially effective at introducing the concepts of BLAST and phylogenetic trees and that students valued and felt inspired by the opportunity to conduct hands-on work and to participate in community science.

Severe clinical mastitis is a frequent disease of dairy cattle. An effective mean of predicting survival despite treatment would be helpful for making euthanasia decisions in poor prognosis cases. The objective was to develop a nomogram for prediction of death or culling in the 60 days following a severe mastitis episode in dairy cows at first veterinary visit in farm settings. A total of 224 dairy cows presenting severe clinical mastitis and examined for the first time by a veterinarian were included in a prospective study. Clinical and laboratory (complete blood cell count, L-lactate, cardiac troponin I, milk culture) variables were recorded. Animals were followed for 60 days. A nomogram was built with an adaptive elastic-net Cox proportional hazards model. Performances and relevance were evaluated by area under the receiver operating characteristic curve (AUC), Harrell’s concordance index (C-index), calibration curve, decision curve analysis (DCA) and misclassification cost term (MCT). The nomogram included: lactation number, recumbency, depression intensity, capillary refilling time, ruminal motility rate, dehydration level, lactates concentration, hematocrit, band neutrophils count, monocyte count, and milk bacteriology. The AUC and C-index showed a good calibration and ability to discriminate. The DCA suggested that the nomogram was clinically relevant. Euthanizing animals having less than 25% probability of survival is economically optimal. It could be used for early euthanasia decisions in animals that would not survive despite treatment. To facilitate the use of this nomogram by veterinarians, a web-based app was developed.

BackgroundMitochondrial disorders (MD) are metabolic diseases related to genetic mutations in mitochondrial DNA and nuclear DNA that cause dysfunction of the mitochondrial respiratory chain. Cognitive impairment and psychiatric symptoms are frequently associated with MD in the adult population. The aim of this study is to describe the neuropsychological profile in children and adolescents with MD.MethodsWe prospectively recruited a sample of 12 children and adolescents between February 2019 and February 2020 in the Reference Center for Mitochondrial Disorders of Angers (France). Participants and their parents completed an anamnestic form describing socio-demographic data and completed the WISC-V (Wechsler Intelligence Scale for Children, 5th edition) and the Parent and Teacher forms of the BRIEF (Behavior Rating Inventory of Executive Function).ResultsIn our sample, the mean IQ (Intellectual Quotient) score was 87.3 ± 25.3. The score ranged from 52 to 120. Concerning executive functions, a significant global clinical complaint was found for parents (six times more than normal) and to a lesser extent, for teachers (among 3 to 4 times more). Levels of intelligence and executive functioning were globally linked in our cohort but dissociation remains a possibility.ConclusionThe results of this study show that MD can be associated to neuropsychological disorders in children and adolescents, especially regarding the intelligence quotient and the executive function. Our study also highlights the need for regular neuropsychological assessments in individuals with MD and developing brains, such as children and adolescents.

Regulation of gene expression requires the combinatorial binding of sequence-specific transcription factors (TFs) at promoters and enhancers. Prior studies showed that alterations in the spacing between TF binding sites can influence promoter and enhancer activity. However, the relative importance of TF spacing alterations resulting from naturally occurring insertions and deletions (InDels) has not been systematically analyzed. To address this question, we first characterized the genome-wide spacing relationships of 73 TFs in human K562 cells as determined by ChIP-seq (chromatin immunoprecipitation sequencing). We found a dominant pattern of a relaxed range of spacing between collaborative factors, including 45 TFs exclusively exhibiting relaxed spacing with their binding partners. Next, we exploited millions of InDels provided by genetically diverse mouse strains and human individuals to investigate the effects of altered spacing on TF binding and local histone acetylation. These analyses suggested that spacing alterations resulting from naturally occurring InDels are generally tolerated in comparison to genetic variants directly affecting TF binding sites. To experimentally validate this prediction, we introduced synthetic spacing alterations between PU.1 and C/EBPβ binding sites at six endogenous genomic loci in a macrophage cell line. Remarkably, collaborative binding of PU.1 and C/EBPβ at these locations tolerated changes in spacing ranging from 5 bp increase to >30 bp decrease. Collectively, these findings have implications for understanding mechanisms underlying enhancer selection and for the interpretation of non-coding genetic variation.

Global Integrated Assessment Models (IAMs) used to characterise mitigation pathways have very limited or no formal representation of lifestyles and lifestyle change. We demonstrate a novel approach to endogenously simulating low-carbon lifestyle heterogeneity and lifestyle change through soft-coupling with our new empirically-based LIFE model. Coupling LIFE to global IAMs enables dynamic simulation of distinctive lifestyle change contributions to targeted mitigation strategies. We set out the empirical basis of the LIFE model, the methodological steps for soft-coupling to a global IAM, and show results from a test application to the residential sector using the MESSAGEix-Buildings model. A first key insight is that coupling with the LIFE model introduces heterogeneous behaviour between ‘engaged’ types, who experience faster and higher reductions in final energy demand compared to ‘disengaged’ types. When we further simulate a widespread shift in normative values, this gap is closed. A second key insight is that drivers of lifestyle change, act differently across ‘Improve’ and ‘Avoid’ dimensions. The ‘disengaged’ types, characterised by lower incomes, are more highly responsive to energy saving ‘Avoid’ behaviours. Our approach demonstrates how improved understanding of lifestyle change dynamics and more realistic, empirically-based quantitative simulations in climate mitigation pathways enriches scientific and policy analysis of how to achieve Paris Climate Agreement goals.

We report the case of a 77-year-old man who presented with successive aortic aneurysms during a 12-year period. He was first treated in 2006 for an abdominal aortic aneurysm with a bifurcated endograft, then in 2016 for a tender type IV thoracoabdominal aortic aneurysm with a proximal aortic cuff with in situ laser fenestrations. He presented in 2018 with a 9-cm distal thoracic aorta aneurysm managed by an off-the-shelf t-Branch endograft (Cook Medical, Bloomington, Ind). The perioperative course was uneventful, and 6-month follow-up computed tomography scan has shown freedom from endoleaks and branch patency. This case illustrates that apparently “healthy” aortic necks can degenerate after endovascular aneurysm repair. Keywords: Aneurysm, Abdominal aorta, Branched stent graft, Endograft, Thoracic endovascular aortic repair, Reintervention

The current definition of osteoporosis includes alteration of bone quality. The assessment of bone quality is improved by the development of new texture analysis softwares. Our objectives were to assess if proximal femoral trabecular bone texture measured in Ultra high field (UHF) 7 Tesla MRI and CT scan were related to biomechanical parameters, and if the combination of texture parameters and areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry provided a better prediction of femoral failure than aBMD alone. The aBMD of 16 proximal femur ends from eight cadavers were investigated. Nineteen textural parameters were computed in three regions or volumes of interest for each specimen on UHF MRI and CT scan. Then, the corresponding failure load and failure stress were calculated thanks to mechanical compression test. aBMD was not correlated to failure load (R2 = 0.206) and stress (R2 = 0.153). The failure load was significantly correlated with ten parameters in the greater trochanter using UHF MRI, and with one parameter in the neck and the greater trochanter using CT scan. Eight parameters in the greater trochanter using UHF MRI combined with aBMD improved the failure load prediction, and seven parameters improved the failure stress prediction. Our results suggest that textural parameters provide additional information on the fracture risk of the proximal femur when aBMD is not contributive.

Background: Mitochondrial disorders (MD) are a group of clinically heterogeneous genetic disorders resulting from dysfunction of the mitochondrial respiratory chain. Cognitive impairment is a common feature in adults with MD and psychiatric symptoms are associated with MD in up to 70% of the adult population. The aim of this study is to describe the psychiatric profile in children and adolescents with MD by focusing on the description of psychiatric symptoms.Methods: A cohort of 12 children and adolescents was prospectively recruited between February 2019 and February 2020 in the Reference Center for Mitochondrial Disorders of Angers (France). Participants and their parents completed an anamnestic form to provide socio-demographic data and completed the Global Assessment of Functioning scale, the Brief Psychiatric Rating Scale, the Child Depression Inventory, the Revised Children's Manifest Anxiety Scale, and the Conner's Rating Scale to evaluate the inattention/hyperactivity symptoms as well as the Quality of Life scale.Results: Four children (33.3%) were diagnosed with depressive symptoms. With regarding to anxiety, 6 children (50%) reported anxiety issues during the psychiatric interview and 3 children (25%) were suffering from anxiety according to the RCMAS scale. Compared to other children with chronic illnesses, the individuals in our cohort reported a lower overall quality of life score and lower scores in physical and social subscales.Conclusion: Our study shows that MD can lead to psychiatric disorders in children and adolescents, in particular anxiety and depression, as well as poor quality of life. This highlights the need for regular psychiatric assessments in individuals with developing brains, such as children and adolescents. We do not, however, have data regarding the neuropsychological profile of this population.

Abstract Background Plant protoplasts are basic plant cells units in which the pecto-cellulosic cell wall has been removed, but the plasma membrane is intact. One of the main features of plant cells is their strong plasticity, and their propensity to regenerate an organism from a single cell. Methods and differentiation protocols used in plant physiology and biology usually involve macroscopic vessels and containers that make difficult, for example, to follow the fate of the same protoplast all along its full development cycle, but also to perform continuous studies of the influence of various gradients in this context. These limits have hampered the precise study of regeneration processes. Results Herein, we present the design of a comprehensive, physiologically relevant, easy-to-use and low-cost microfluidic and microscopic setup for the monitoring of Physcomitrella patens (P. patens) growth and development on a long-term basis. The experimental solution we developed is made of two parts (i) a microfluidic chip composed of a single layer of about a hundred flow-through microfluidic traps for the immobilization of protoplasts, and (ii) a low-cost, light-controlled, custom-made microscope allowing the continuous recording of the moss development in physiological conditions. We validated the experimental setup with three proofs of concepts: (i) the kinetic monitoring of first division steps and cell wall regeneration, (ii) the influence of the photoperiod on growth of the protonemata, and (iii) finally the induction of leafy buds using a phytohormone, cytokinin. Conclusions We developed the design of a comprehensive, physiologically relevant, easy-to-use and low-cost experimental setup for the study of P. patens development in a microfluidic environment. This setup allows imaging of P. patens development at high resolution and over long time periods.

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a condition characterized by the repeated growth of benign exophytic papilloma in the respiratory tract. The course of the disease remains unpredictable: some children experience minor symptoms, while others require multiple interventions due to florid growth. Our study aimed to identify histologic severity risk factors in patients with JoRRP. Forty-eight children from two French pediatric centers were included retrospectively. Criteria for a severe disease were: annual rate of surgical endoscopy ≥ 5, spread to the lung, carcinomatous transformation or death. We conducted a multi-stage study with image analysis. First, with Hematoxylin and eosin (HE) digital slides of papilloma, we searched for morphological patterns associated with a severe JoRRP using a deep-learning algorithm. Then, immunohistochemistry with antibody against p53 and p63 was performed on sections of FFPE samples of laryngeal papilloma obtained between 2008 and 2018. Immunostainings were quantified according to the staining intensity through two automated workflows: one using machine learning, the other using deep learning. Twenty-four patients had severe disease. For the HE analysis, no significative results were obtained with cross-validation. For immunostaining with anti-p63 antibody, we found similar results between the two image analysis methods. Using machine learning, we found 23.98% of stained nuclei for medium intensity for mild JoRRP vs. 36.1% for severe JoRRP (p = 0.041); and for medium and strong intensity together, 24.14% for mild JoRRP vs. 36.9% for severe JoRRP (p = 0.048). Using deep learning, we found 58.32% for mild JoRRP vs. 67.45% for severe JoRRP (p = 0.045) for medium and strong intensity together. Regarding p53, we did not find any significant difference in the number of nuclei stained between the two groups of patients. In conclusion, we highlighted that immunochemistry with the anti-p63 antibody is a potential biomarker to predict the severity of the JoRRP.

The study of eye movements is a common way to non-invasively understand and analyze human behavior. However, eye-tracking techniques are very hard to scale, and require expensive equipment and extensive expertise. In the context of web browsing, these issues could be overcome by studying the link between the eye and the computer mouse. Here, we propose new analysis methods, and a more advanced characterization of this link. To this end, we recorded the eye, mouse, and scroll movements of 151 participants exploring 18 dynamic web pages while performing free viewing and visual search tasks for 20 s. The data revealed significant differences of eye, mouse, and scroll parameters over time which stabilize at the end of exploration. This suggests the existence of a task-independent relationship between eye, mouse, and scroll parameters, which are characterized by two distinct patterns: one common pattern for movement parameters and a second for dwelling/fixation parameters. Within these patterns, mouse and eye movements remained consistent with each other, while the scrolling behaved the opposite way.

In this paper, we show that a basic fixed point method used to enclose the greatest fixed point in a Kleene algebra will allow us to compute inner and outer approximations of invariant-based sets for continuous-time nonlinear dynamical systems. Our contribution is to provide the definitions and theorems that will allow us to make the link between the theory of invariant sets and the Kleene algebra. This link has never be done before and will allow us to compute rigorously sets that can be defined as a combination of positive invariant sets. Some illustrating examples show the nice properties of the approach.

Summary: BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses reveals a deficit in presynaptic release probability and slower depletion of neurotransmitters during repetitive stimulation, suggesting altered vesicle dynamics in Bin1 cKO mice. Super-resolution and immunoelectron microscopy localizes BIN1 to presynaptic sites in excitatory synapses. Bin1 cKO significantly reduces synapse density and alters presynaptic active zone protein cluster formation. Finally, 3D electron microscopy reconstruction analysis uncovers a significant increase in docked and reserve pools of synaptic vesicles at hippocampal synapses in Bin1 cKO mice. Our results demonstrate a non-redundant role for BIN1 in presynaptic regulation, thus providing significant insights into the fundamental function of BIN1 in synaptic physiology relevant to Alzheimer disease. : BIN1 is a significant risk factor for late-onset Alzheimer disease. BIN1 has a general role in endocytosis and membrane dynamics in non-neuronal cells. De Rossi et al. show that BIN1 localizes to presynaptic terminals and plays an indispensable role in excitatory synaptic transmission by regulating neurotransmitter vesicle dynamics. Keywords: late-onset Alzheimer disease, BIN1, Morris water maze, synaptic physiology, release probability, super-resolution, dSTORM, STED, 3D EM reconstruction, Amphiphysin 2

Marine organisms show population structure at a relatively fine spatial scale, even in open habitats. The tools commonly used to assess subtle patterns of connectivity have diverse levels of resolution and can complement each other to inform on population structure. We assessed and compared the discriminatory power of genetic markers and otolith shape to reveal the population structure on evolutionary and ecological time scales of the common sole (Solea solea), living in the Eastern English Channel (EEC) stock off France and the UK. First, we genotyped fish with Single Nucleotide Polymorphisms to assess population structure at an evolutionary scale. Then, we tested for spatial segregation of the subunits using otolith shape as an integrative tracer of life history. Finally, a supervised machine learning framework was applied to genotypes and otolith phenotypes to probabilistically assign adults to subunits and assess the discriminatory power of each approach. Low but significant genetic differentiation was found among subunits. Moreover, otolith shape appeared to vary spatially, suggesting spatial population structure at fine spatial scale. However, results of the supervised discriminant analyses failed to discriminate among subunits, especially for otolith shape. We suggest that the degree of population segregation may not be strong enough to allow for robust fish assignments. Finally, this study revealed a weak yet existing metapopulation structure of common sole at the fine spatial scale of the EEC based on genotypes and otolith shape, with one subunit being more isolated. Our study argues for the use of complementary tracers to investigate marine population structure.

The ALCYONE multidimensional fuel performance code codeveloped by the CEA, EDF, and AREVA NP within the PLEIADES software environment models the behavior of fuel rods during irradiation in commercial pressurized water reactors (PWRs), power ramps in experimental reactors, or accidental conditions such as loss of coolant accidents or reactivity-initiated accidents (RIAs). As regards the latter case of transient in particular, ALCYONE is intended to predictively simulate the response of a fuel rod by taking account of mechanisms in a way that models the physics as closely as possible, encompassing all possible stages of the transient as well as various fuel/cladding material types and irradiation conditions of interest. On the way to complying with these objectives, ALCYONE development and validation shall include tests on PWR-UO2 fuel rods with advanced claddings such as M5® under “low pressure–low temperature” or “high pressure–high temperature” water coolant conditions.This article first presents ALCYONE V1.4 RIA-related features and modeling. It especially focuses on recent developments dedicated on the one hand to nonsteady water heat and mass transport and on the other hand to the modeling of grain boundary cracking-induced fission gas release and swelling. This article then compares some simulations of RIA transients performed on UO2-M5® fuel rods in flowing sodium or stagnant water coolant conditions to the relevant experimental results gained from tests performed in either the French CABRI or the Japanese NSRR nuclear transient reactor facilities. It shows in particular to what extent ALCYONE—starting from base irradiation conditions it itself computes—is currently able to handle both the first stage of the transient, namely the pellet-cladding mechanical interaction phase, and the second stage of the transient, should a boiling crisis occur.Areas of improvement are finally discussed with a view to simulating and analyzing further tests to be performed under prototypical PWR conditions within the CABRI International Program.M5® is a trademark or a registered trademark of AREVA NP in the USA or other countries. Keywords: Pressurized Water Reactor, Nuclear Fuel, UO2, M5®, Reactivity-initiated Accident, ALCYONE Code

Underwater acoustic communication is a key point for performance improvement in an autonomous underwater vehicle (AUV) swarm. The communication process is essential for improving the AUVs localization accuracy for navigation and is a convenient way for sharing information among the AUVs in a network. The objective of this work, which was developed in the COMET and NEMOSENS projects, is to address the communication process required in a mobile underwater wireless network, with a focus on the proposal of an adaptive physical layer methodology. We discuss about the employed channel access method, the frame structure, and we propose the usage of an adaptive guard interval in order to ameliorate the network usage rate. We explain the physical layer aspect of the communication: the data processing at the transmitter and receiver side. In addition to that, we propose the usage of smart communications among AUVs. We design a method for adapting some physical layer parameters. The proposed approach relies only on the knowledge of the transmission geometry, and it optimizes the number of subcarriers and the cyclic-prefix length of the Orthogonal Frequency-Division Multiplexing (OFDM) system. The obtained results show a performance improvement in terms of bit-error rate when compared with the case of random parameters selection. These results corroborate the benefits of our adaptive parameters approach.

Generally, fluorescence imaging needs to be done in a dark environment using molecules with spectrally separated emissions. Here, Quérard et al. develop a protocol for high-speed imaging and remote sensing of spectrally overlapping reversible photoswitchable fluorophores in ambient light.