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Abstract The resonant single active bridge topology (R‐SAB) operated in the half‐cycle discontinuous current mode (HC‐DCM) is a very attractive solution due to its high efficiency, low complexity and fixed voltage transfer ratio (DCX). However, as expected for a series‐resonant converter (SRC), its DCX operation depends on the resonant tank circuit‐parameters, parasitic capacitive elements and output load. Specially, at light and no‐load operation, when the system is extremely underdamped, it may present a large output overvoltage due to resonance interactions. This is of prime importance for converters using medium voltage (MV) SiC‐MOSFETs, which feature significant output capacitances that can lead to voltage breakdown of the rectifier semiconductors. Therefore, the supposed fixed‐voltage transfer ratio is not entirely valid and deserves a proper understanding due its criticality. This paper reviews the subject, clarifying its root cause and its multifactorial dependencies. Moreover, it provides a simple solution based on a variable dead‐time with fixed magnetizing current experimentally verified with a 300kW/1.8kV R‐SAB prototype implemented with MV SiC‐devices.

This paper assesses the sustainability of planned water uses in mesoscale river basins under multiple climate change scenarios, and contributes to determining the possible causes of unsustainability. We propose an assessment grounded in real-world water management issues, with water management scenarios built in collaboration with local water agencies. Furthermore, we present an analysis through indicators that relate to management goals and present the implications of climate uncertainty for our results, furthering the significance of our study for water management. A modeling framework integrating hydro-climatic and human dynamics and accounting for interactions between resource and demand was applied in two basins of different scales and with contrasting water uses: the Herault (2500 km2, France) and the Ebro (85 000 km2, Spain) basins. Natural streamflow was evaluated using a conceptual hydrological model. A demand-driven reservoir management model was designed to account for streamflow regulations from the main dams. Human water demand was estimated from time series of demographic, socioeconomic and climatic data. Environmental flows were accounted for by defining streamflow thresholds under which withdrawals were strictly limited. Finally indicators comparing water availability to demand at strategic resource and demand nodes were computed. This framework was applied under different combinations of climatic and water use scenarios for the mid-21st to differentiate the impacts of climate- and human-induced changes on streamflow and water balance. Results showed that objective monthly environmental flows would be guaranteed in current climate conditions in both basins, yet in several areas this could imply limiting human water uses more than once every 5 years. The impact of the tested climate projections on both water availability and demand could question the water allocations and environmental requirements currently planned for the coming decades. Water shortages for human use could become more frequent and intense, and the pressure on water resources and aquatic ecosystems could intensify. The causes of unsustainability vary across sub-basins and scenarios, and in most areas results are highly dependent on the climate change scenario.

This study assesses water stress by 2050 in river basins facing increasing human and climatic pressures, by comparing the impacts of various combinations of possible future socio-economic and climate trends. A modelling framework integrating human and hydro-climatic dynamics and accounting for interactions between resource and demand at a 10-day time step was developed and applied in two basins of different sizes and with contrasted water uses: the Herault (2500 km2, France) and the Ebro (85 000 km2, Spain) basins. Natural streamflow was evaluated using a conceptual hydrological model (GR4j). A demand-driven reservoir management model was designed to account for streamflow regulations from the main dams. Urban water demand was estimated from time series of population and monthly unit water consumption data. Agricultural water demand was computed from time series of irrigated area, crop and soil data, and climate forcing. Indicators comparing water supply to demand at strategic resource and demand nodes were computed. This framework was successfully calibrated and validated under non-stationary human and hydro-climatic conditions over the last 40 years before being applied under four combinations of climatic and water use scenarios to differentiate the impacts of climate- and human-induced changes on streamflow and water balance. Climate simulations from the CMIP5 exercise were used to generate 18 climate scenarios at the 2050 horizon. A baseline water use scenario for 2050 was designed based on demographic and local socio-economic trends. Results showed that projected water uses are not sustainable under climate change scenarios.

In this study we present an integrative modeling framework aimed at assessing the balance between water demand and availability and its spatial and temporal variability over long time periods. The model was developed and tested over the period 1971–2009 in the Hérault (2500 km2, France) and the Ebro (85 000 km2, Spain) catchments. Natural streamflow was simulated using a conceptual hydrological model. The regulation of river flow was accounted for through a widely applicable demand-driven reservoir management model applied to the largest dam in the Hérault Basin and to 11 major dams in the Ebro Basin. Urban water demand was estimated from population and monthly unit water demand data. Water demand for irrigation was computed from irrigated area, crop and soil data, and climatic forcing. Water shortage was assessed at a 10-day time step by comparing water demand and availability through indicators calculated at strategic resource and demand nodes. The outcome of this study is twofold. First, we were able to correctly simulate variations in influenced streamflow, reservoir levels and water shortage between 1971 and 2009 in both basins, taking into account climatic and anthropogenic pressures and changes in water management strategies over time. Second, we provided information not available through simple data analysis on the influence of withdrawals and consumptive use on streamflow and on the drivers of imbalance between demand and availability. Observed past variations in discharge were explained by separating anthropogenic and climatic pressures in our simulations: 3% (20%) of the decrease in the Hérault (Ebro) discharge were linked to anthropogenic changes. Although key areas of the Hérault Basin were shown to be highly sensitive to hydro-climatic variability, the balance between water demand and availability in the Ebro Basin appears to be more critical, owing to high agricultural pressure on water resources. The modeling framework developed and tested in this study will be used to assess water balance under climatic and socioeconomic prospective scenarios and to investigate the effectiveness of adaptation policies aimed at maintaining the balance between water demand and availability.

BACKGROUND AND OBJECTIVES: In the Colombian Caribbean, some rural communities rely on self-generated energy due to their lack of connection to the national grid. This energy generated is achieved through a combination of combustion engines and renewable sources. However, certain communities face challenges maintaining daily energy autonomy, resulting in developmental disparities. Consequently, the research aims to develop a strategy for assessing renewable resource availability and conducting risk analysis to support the implementation of electrification initiatives in rural areas of the Colombian Caribbean.METHODS: A review was made of the feasibility of financing projects with a focus on renewable energies by government financing entities in Colombia. Subsequently, risk management was applied in projects of this nature, assessing the renewable potentials available in the region, such as wind and photovoltaic solar energy.FINDINGS: Of the risks encountered, political risk is the main reason why projects focused on renewable energy in the Colombian Caribbean do not end in a good state of operation, although there is a good exploitable solar and wind energy potential in the region as indicated by the statistical analyses carried out with the records obtained by meteorological instrumentation of the area. Presenting potential solar radiation levels ranging from 5 kilowatt-hours per square meter per day, and wind speeds exceeding 2 and 7 meters per second in certain localities. This indicates that the signed projects are supported with inadequate dimensioning.CONCLUSION: The routes established to perform good management for the energization of these populations are presented, when evaluating the wind and solar potentials available by location, and the risk analysis which indicates that, for such proposals political and financial risks present the greatest uncertainty. The solar radiation potentials obtained are suitable for proper sizing of photovoltaic systems, and the wind speeds identified suggest a review of how to harness these wind potentials effectively.

With the advent of modern non-destructive tomography techniques, there have been many attempts to analyze 3-D pore space features mainly concentrating on soil structure. This analysis opens a challenging opportunity to develop techniques for quantifying and describe pore space properties, one of them being fractal analysis. Undisturbed soil samples were collected from four horizons of Brazilian soil and 3-D images at 45 μm resolution. Four different threshold criteria were used to transform computed tomography (CT) grey-scale imagery into binary imagery (pore/solid) to estimate their mass fractal dimension (Dm) and entropy dimension (D1). Each threshold criteria had a direct influence on the porosity obtained, varying from 8 to 24% in one of the samples, and on the fractal dimensions. Linear scaling was observed over all the cube sizes, however depending on the range of cube sizes used in the analysis, Dm could vary from 3.00 to 2.20, realizing that the threshold influenced mainly the scaling in the smallest cubes (length of size from 1 to 16 voxels). Dm and D1 showed a logarithmic relation with the apparent porosity in the image, however, the increase of both values respect to porosity defined a characteristic feature for each horizon that can be related to soil texture and depth.

Objectives: to highlight an infrequent occurrence using a series of clinical cases with symptoms and signs, and specific radiological findings allowing its diagnosis and treatment, which is in most cases successful. Patients and methods: a descriptive and retrospective study of patients diagnosed by computed tomography scanning and then treated with surgery in the Pancreas and Biliary Unit of a University Hospital from March 1999 to September 2005. Results: there were 6 female patients with a mean age of 33.5 years (range 11-72). Most common signs included pain and a palpable mass in the abdomen. Three patients were diagnosed by computed tomography scanning, and a differential diagnosis with a neuroendocrine tumor was performed for the remaining three subjects. Surgical treatment was adapted to each patient according to the findings and images seen in their computed tomography scans. Biopsy results confirmed the presumed diagnoses, and showed one case of solid pseudopapillary carcinoma of the pancreas. Average hospital stay was of 18.16 days (range 8-30). Mortality rate was 0%. No recurrences occurred during follow-up for 46.3 months on average (range 12-76). Conclusions: the presence of a huge mass in the pancreas of a young female should prompt suspicion for a solid pseudopapillary tumor. Given its low malignant potential, and the presence of specific radiographic patterns, its diagnosis should be accurate, as radical surgical treatment is effective.

Background: APACHE II is a multifactorial scoring system for predicting severity in acute pancreatitis (AP). Organ failure (OF) has been correlated with mortality in AP. Objectives: to evaluate the usefulness of APACHE II as an early predictor of severity in AP, its correlation with OF, and the relevance of an early establishment of OF during the course of AP. Patients and methods: from January 1999 to November 2001, 447 consecutive cases of AP were studied. APACHE II scores and Atlanta criteria were used for defining severity and OF. Results: twenty-five percent of patients had severe acute pancreatitis (SAP). APACHE II at 24 h after admission showed a sensitivity, specificity, and positive and negative predictive value of 52, 77, 46, and 84%, respectively, for predicting severity. Mortality for SAP was 20.5%. Seventy percent of patients who developed OF did so within the first 24 hours of admission, and their mortality was 52%. Mortality was statistically significant (p < 0.01) if OF was established within the first 24 hours after admission. Conclusions: APACHE II is not reliable for predicting outcome within the first 24 hours after admission and should therefore be used together with other methods. OF mostly develops within the first days after admission, if ever. The time of onset of OF is the most accurate and reliable method for predicting death risk in AP.Introducción: el APACHE II se ha utilizado como factor predictivo de gravedad en la pancratitis aguda (PA). La instauración de fracaso orgánico (FO) en la PA se correlaciona con una mayor mortalidad. Objetivos: evaluar la utilidad del APACHE II como factor predictivo precoz de gravedad en la PA, su correlación con el FO y la relevancia del establecimiento precoz del FO en la PA. Pacientes y métodos: desde enero de 1999 hasta noviembre de 2001 se estudiaron 447 pacientes ingresados consecutivamente por PA. Se utilizó el sistema APACHE II y los criterios de Atlanta para evaluar la gravedad. Resultados: el 25% de los pacientes presentaron una pancreatitis aguda grave (PAG). El APACHE II a las 24 horas del ingreso mostró una sensibilidad, especificidad, valor predictivo positivo y negativo del 52, 77, 46 y 84%, respectivamente, como marcador de gravedad. La mortalidad global de la PAG fue del 20,5%. El 70% de los pacientes que presentaron FO lo hicieron en las primeras 24 horas del ingreso, falleciendo el 52% de ellos. La mortalidad fue significativamente mayor (p < 0,01) si el FO se estableció en ese periodo. Conclusiones: el APACHE II por si solo no es un sistema fiable de detección precoz de gravedad en las primeras 24 horas del ingreso por lo que debe utilizarse junto con otros métodos. El FO suele establecerse en los primeros días del curso evolutivo de la PA. La precocidad del establecimiento del FO muestra una estrecha relación con la mortalidad en la PA.

Objective To assess the impact of changes in use of care and implementation of hospital reorganisations spurred by the COVID-19 pandemic (first wave) on the acute management times of patients who had a stroke and ST-segment elevation myocardial infarction (STEMI).Design Two cohorts of patients who had an STEMI and stroke in the Aquitaine Cardio-Neuro-Vascular (CNV) registry.Setting 6 emergency medical services, 30 emergency units (EUs), 14 hospitalisation units and 11 cathlabs in the Aquitaine region.Participants This study involved 9218 patients (6436 patients who had a stroke and 2782 patients who had an STEMI) in the CNV Registry from January 2019 to August 2020.Method Hospital reorganisations, retrieved in a scoping review, were collected from heads of hospital departments. Other data were from the CNV Registry. Associations between reorganisations, use of care and care management times were analysed using multivariate linear regression mixed models. Interaction terms between use-of-care variables and period (pre-wave, per-wave and post-wave) were introduced.Main outcome measures STEMI cohort, first medical contact-to-procedure time; stroke cohort, EU admission-to-imaging time.Results Per-wave period management times deteriorated for stroke but were maintained for STEMI. Per-wave changes in use of care did not affect STEMI management. No association was found between reorganisations and stroke management times. In the STEMI cohort, the implementation of systematic testing at admission was associated with a 41% increase in care management time (exp=1.409, 95% CI 1.075 to 1.848, p=0.013). Implementation of plan blanc, which concentrated resources in emergency activities, was associated with a 19% decrease in management time (exp=0.801, 95% CI 0.639 to 1.023, p=0.077).Conclusions The pandemic did not markedly alter the functioning of the emergency network. Although stroke patient management deteriorated, the resilience of the STEMI pathway was linked to its stronger structuring. Transversal reorganisations, aiming at concentrating resources on emergency care, contributed to maintenance of the quality of care.Trial registration number NCT04979208.

Abstract Background Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hox genes from the HoxD cluster is differentially controlled in space and time, in cells that will pattern the digits and the forearms. While the Hoxd genes broadly share a common regulatory landscape and large-scale analyses have suggested a homogenous Hox gene transcriptional program, it has not previously been clear whether Hoxd genes are expressed together at the same levels in the same cells. Results We report a high degree of heterogeneity in the expression of the Hoxd11 and Hoxd13 genes. We analyzed single-limb bud cell transcriptomes and show that Hox genes are expressed in specific combinations that appear to match particular cell types. In cells giving rise to digits, we find that the expression of the five relevant Hoxd genes (Hoxd9 to Hoxd13) is unbalanced, despite their control by known global enhancers. We also report that specific combinatorial expression follows a pseudo-time sequence, which is established based on the transcriptional diversity of limb progenitors. Conclusions Our observations reveal the existence of distinct combinations of Hoxd genes at the single-cell level during limb development. In addition, we document that the increasing combinatorial expression of Hoxd genes in this developing structure is associated with specific transcriptional signatures and that these signatures illustrate a temporal progression in the differentiation of these cells.

Abstract Background The transcriptional activation of HoxD genes during mammalian limb development involves dynamic interactions with two topologically associating domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior HoxD genes in developing digits is controlled by regulatory elements located in the centromeric TAD (C-DOM) through long-range contacts. Results To assess the structure–function relationships underlying such interactions, we measured compaction levels and TAD discreteness using a combination of chromosome conformation capture (4C-seq) and DNA FISH. We assessed the robustness of the TAD architecture by using a series of genomic deletions and inversions that impact the integrity of this chromatin domain and that remodel long-range contacts. We report multi-partite associations between HoxD genes and up to three enhancers. We find that the loss of native chromatin topology leads to the remodeling of TAD structure following distinct parameters. Conclusions Our results reveal that the recomposition of TAD architectures after large genomic re-arrangements is dependent on a boundary-selection mechanism in which CTCF mediates the gating of long-range contacts in combination with genomic distance and sequence specificity. Accordingly, the building of a recomposed TAD at this locus depends on distinct functional and constitutive parameters.

Prostate cancer (PCa) is one of the most common cancers in men. Metastasis is the leading cause of death in prostate cancer patients. One of the crucial processes involved in metastatic spread is the "epithelial-mesenchymal transition" (EMT), which allows cells to acquire the ability to invade distant organs. Liver X Receptors (LXRs) are nuclear receptors that have been demonstrated to regulate EMT in various cancers, including hepatic cancer. Our study reveals that the LXR pathway can control pro-invasive cell capacities through EMT in prostate cancer, employing ex vivo and in vivo approaches. We characterized the EMT status of the commonly used LNCaP, DU145, and PC3 prostate cancer cell lines through molecular and immunohistochemistry experiments. The impact of LXR activation on EMT function was also assessed by analyzing the migration and invasion of these cell lines in the absence or presence of an LXR agonist. Using in vivo experiments involving NSG-immunodeficient mice xenografted with PC3-GFP cells, we were able to study metastatic spread and the effect of LXRs on this process. LXR activation led to an increase in the accumulation of Vimentin and Amphiregulin in PC3. Furthermore, the migration of PC3 cells significantly increased in the presence of the LXR agonist, correlating with an upregulation of EMT. Interestingly, LXR activation significantly increased metastatic spread in an NSG mouse model. Overall, this work identifies a promoting effect of LXRs on EMT in the PC3 model of advanced prostate cancer.

Study Objective: Interpretation of gastric ultrasound relies on the use of a clinical algorithm that combines qualitative analysis of the gastric antrum contents with the calculation of the volume of fluid contents. This reference method may be difficult to apply in the parturient. We therefore aimed to assess the diagnostic accuracy of a simple qualitative assessment in the supine position for the diagnosis of high-risk gastric contents in the parturient. We also assessed the diagnostic accuracy of a composite scale and another clinical algorithm based on a mathematical model different to that used in the reference method., Design: Prospective observational cohort study., Setting: University hospital, Lyon, France., Patients: Adult women admitted to the delivery room., Interventions: Qualitative and quantitative gastric ultrasound examination within the first hour following admission., Measurements: With respect to the reference method, the diagnostic accuracy of a simple qualitative assessment for the diagnosis of high-risk gastric contents was assessed. The diagnostic accuracy of a composite scale and another clinical algorithm, and the agreement between each approach were also assessed., Main Results: A total of 235 parturients were included and analyzed. The simple qualitative assessment led to conclusive ultrasound assessment in 233 (99%) women, while the reference method led to conclusive assessment in 213 (91%) women (P < 0.05). The sensitivity and the specificity of the simple qualitative assessment were 97% (95%CI: 93 to 99%) and 96% (95%CI: 90 to 99%), respectively. These were not significantly different from those of the composite scale and the clinical algorithm. The four approaches showed almost perfect agreement with each other., Conclusions: These results suggest that simple qualitative assessment may be useful in clinical practice to help the anesthesiologist in the assessment of gastric contents status and risk of aspiration., Competing Interests: Declaration of competing interest Lionel Bouvet and Laurent Zieleskiewicz received lecture expenses from GE Healthcare. Other authors declare that they have no conflict of interest. This study was solely supported by institutional funding. No grants were received from any funding agencies in the public, commercial, or non-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This multicentre prospective observational study sought to determine the prevalence and the factors associated with high-risk gastric contents in women admitted to the maternity unit for childbirth, and to identify the clinical situations in which ultrasound assessment of gastric contents would be most helpful (i.e. when the prevalence of high-risk gastric contents is close to 50%)., Methods: Ultrasound assessments of gastric contents were performed within the first hour after admission to the maternity unit. The prevalence of high-risk gastric contents was calculated and variables associated with high-risk gastric contents were identified using logistic regression analyses., Results: A total of 1003 parturients were analysed. The prevalence of high-risk gastric contents was 70% (379/544; 95% confidence interval: 66-74%) in women admitted in spontaneous labour and 65% (646/1003; 95% confidence interval: 61-67%) in the whole cohort. Lower gestational age, increased fasting duration for solids, and elective Caesarean delivery were independently associated with reduced likelihood of high-risk gastric contents. In women admitted in spontaneous labour and in the whole cohort, the prevalence of high-risk gastric contents ranged from 85% to 86% for fasting duration for solids <6 h, 63%-68% for fasting 6-8 h, 54%-55% for fasting 8-12 h, and 47%-51% for fasting ≥12 h., Conclusions: Around two-thirds of parturients had high-risk gastric contents within the first hour after admission to the maternity unit. Our results suggest that gastric emptying for solids continues in labouring women, and that gastric ultrasound would be most helpful when fasting duration is ≥8 h., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Intensive cardiac care units (ICCU) were initially developed to monitor ventricular arrhythmias after myocardial infarction. In recent decades, ICCU have diversified their activities., Aim: To determine the type of patients hospitalized in ICCU in France., Methods: We analysed the characteristics of patients enrolled in the ADDICT-ICCU registry (NCT05063097), a prospective study of consecutive patients admitted to ICCU in 39 centres throughout France from 7th-22nd April 2021. In-hospital major adverse events (MAE) (death, resuscitated cardiac arrest and cardiogenic shock) were recorded., Results: Among 1499 patients (median age 65 [interquartile range 54-74] years, 69.6% male, 21.7% diabetes mellitus, 64.7% current or previous smokers), 34.9% had a history of coronary artery disease, 11.7% atrial fibrillation and 5.2% cardiomyopathy. The most frequent reason for admission to ICCU was acute coronary syndromes (ACS; 51.5%), acute heart failure (AHF; 14.1%) and unexplained chest pain (6.8%). An invasive procedure was performed in 36.2%. "Advanced" ICCU therapies were required for 19.9% of patients (intravenous diuretics 18.4%, non-invasive ventilation 6.1%, inotropic drugs 2.3%). No invasive procedures or advanced therapies were required in 44.1%. Cardiac computed tomography or magnetic resonance imaging was carried out in 12.3% of patients. The median length of ICCU hospitalization was 2.0 (interquartile range 1.0-4.0) days. The mean rate of MAE was 4.5%, and was highest in patients with AHF (10.4%)., Conclusions: ACS remains the main cause of admissions to ICCU, with most having a low rate of in-hospital MAE. Most patients experience a brief stay in ICCU before being discharged home. AHF is associated with highest death rate and with higher resource consumption., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events., Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097)., Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p < 0.001). Similar results were found after adjustment for comorbidities (hazard ratio [HR] [95% confidence interval (CI)]): 5.92 [2.43-14.38]) or parameters of in-hospital severity (HR 6.09, 95% CI [2.51-14.80]) and propensity score matching (HR 7.46, 95% CI [1.70-32.8]). CO > 11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56-44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06-28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33-6.98] and 1.66 [0.96-2.85] respectively)., Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events., Funding: Grant from Fondation Coeur & Recherche., Competing Interests: Jean-Guillaume Dillinger, Théo Pezel, Clément Delmas, Guillaume Schurtz, Antonin Trimaille, Nicolas Piliero, Claire Bouleti, Benoit Lattuca, Stéphane Andrieu, Julien Fabre, Reza Rossanaly Vasram, Jean-Claude Dib, Charles Fauvel, Albert Boccara, Etienne Puymirat, Solenn Toupin, Eric Vicaut and Patrick Henry report no conflict of interests. Victor Aboyans reports consulting fees from Astra-Zeneca, honoria for lectures or presentations from Boehringer, Bayer and Novonordisk, participation on a DSMB for Bayer, member of a committee of the European Society of Cardiology and of the French Society of Cardiology. Francois Roubille reports honoria for lectures or presentations from Astra Zeneca, Boehringer, Astra Zeneca, Vifor, Bayer, Pfizer, Novartis, Servier, Novo-Nordisk, Air liquid, Abbott, QuidelOrtho, GSK. Edouard Gerbaud reports consulting fees from Terumo Corporation, Abbott vascular and honoria for lectures from Servier. Authors had full access to all the data in the study and, accept responsibility to submit for publication., (© 2023 Published by Elsevier Ltd.)

Objectives: To describe and compare the initial clinical characteristics of a cohort of patients with suspected COVID-19 managed by general practitioners (GPs); to assess whether 3-month persistent symptoms were more frequent among confirmed cases than among no-COVID cases; and to identify factors predictive of persistent symptoms and adverse outcomes among confirmed cases., Design and Setting: A comparative, prospective, multicentre cohort study in primary care in the Paris region of France., Participants: 521 patients aged ≥18 with suspected COVID-19 were enrolled between March and May 2020., Outcome Measures: Initial symptoms, COVID-19 status, persistent symptoms 3 months after inclusion and a composite criterion for potentially COVID-19-related events (hospitalisation, death, emergency department visits). The final COVID-19 status ('confirmed', 'no-COVID' and 'uncertain' cases) was determined by the GP after the receipt of the laboratory test results., Results: 516 patients were analysed; 166 (32.2%) were classified into the 'confirmed COVID' group, 180 (34.9%) into the 'no-COVID' group and 170 (32.9%) in the 'uncertain COVID' group. Confirmed cases were more likely to have persistent symptoms than no-COVID cases (p=0.09); initial fever/feeling feverish and anosmia were independently associated with persistent symptoms. At 3 months, we observed 16 (9.8%) COVID-19-related hospital admissions, 3 (1.8%) intensive care unit admissions, 13 (37.1%) referrals to an emergency department and no death. Age >70 and/or at least one comorbidity (OR 6.53; 95% CI 1.13-37.84; p=0.036), abnormalities in a lung examination (15.39; 95% CI 1.61-146.77; p=0.057) and two or more systemic symptoms (38.61; 95% CI 2.30-647.40; p=0.011) were associated with the composite criterion., Conclusions: Although most patients with COVID-19 in primary care had mild disease with a benign course, almost one in six had persistent symptoms at 3 months. These symptoms were more frequent in the 'confirmed COVID' group. Our findings need to be confirmed in a prospective study with longer follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cyclin E1 is the regulatory subunit of cyclin-dependent kinase 2 (Cdk2) and one of the central players in cell cycle progression. We recently showed its crucial role for initiation of liver fibrosis and hepatocarcinogenesis. In the present study, we investigated the role of Cyclin E1 in the development of alcohol-associated liver disease (ALD)., Methods: Mice with constitutive (E1 -/- ), hepatocyte-specific (Cyclin E1 Δhepa ), or intestinal-epithelial-cell-specific (Cyclin E1 ΔIEC ) inactivation of Cyclin E1 and corresponding wild type littermate controls (WT) were administered either a Lieber-DeCarli ethanol diet (LDE) for 3 weeks or acute ethanol binges (6 g/kg) through oral gavage. Serum parameters of liver functionality were measured; hepatic tissues were collected for biochemical and histological analyses., Results: The administration of acute EtOH binge and chronic LDE diet to E1 -/- mice enhanced hepatic steatosis, worsened liver damage and triggered body weight loss. Similarly, in the acute EtOH binge model, Cyclin E1 Δhepa mice revealed a significantly worsened liver phenotype. In contrast, inactivation of Cyclin E1 only in intestinal epithelial cell (IECs)did not lead to any significant changes in comparison to WT mice after acute EtOH challenge. Remarkably, both acute and chronic EtOH administration in E1 -/- animals resulted in increased levels of ADH and decreased expression of ALDH1/2. The additional application of a pan-Cdk inhibitor (S-CR8) further promoted liver damage in EtOH-treated WT mice., Conclusion: Our data point to a novel unexpected role of Cyclin E1 in hepatocytes for alcohol metabolism, which seems to be independent of the canonical Cyclin E1/Cdk2 function as a cell cycle regulator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The prevalence of radiation-induced nausea and vomiting varies between 40% and 80%. They have many consequences on treatment and comorbidities. This work thus aimed to define clinical practice guidelines for the management of radiation-induced nausea and vomiting., Methods: XXXXX, XXXX, XXX, XXXXX, XXXX and XXXX compiled a working group who draft these recommendations., Results: The assessment of the emetogenic risk found two main predictive factors: 1) the irradiated anatomical location, 2) an associated concomitant chemotherapy. In the case of exclusive radiotherapy, primary antiemetic prophylaxis depends on the emetogenic risk (the irradiated anatomical location). In the case of concomitant chemotherapy, the emetogenic risk is generally higher and the primary antiemetic prophylaxis corresponds to that of chemotherapy-induced nausea and vomiting. In cases where symptoms persist, remedial treatments are poorly codified., Conclusion: Radiation-induced nausea and vomiting remains underdiagnosed and undertreated, its rapid detection and treatment are essential to reinstate good clinical practice., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Psychoactive drugs, including illicit drugs, are associated with an increased rate of cardiovascular events. The prevalence and outcome of patients using these drugs at the time of admission to an intensive cardiac care unit is unknown., Aim: To assess the prevalence of psychoactive drugs detected in consecutive patients hospitalized in an intensive cardiac care unit for an acute cardiovascular event., Methods: This is a nationwide prospective multicentre study, involving 39 centres throughout France, including all consecutive patients hospitalized in an intensive cardiac care unit within 2weeks. Psychoactive drug use will be assessed systematically by urine drug assay within 2hours of intensive cardiac care unit admission, to detect illicit (cannabinoids, cocaine, amphetamines, ecstasy, heroin and other opioids) and non-illicit (barbiturates, benzodiazepines, tricyclic antidepressants, methadone and buprenorphine) psychoactive drugs. Smoking will be investigated systematically by exhaled carbon monoxide measurement, and alcohol consumption using a standardized questionnaire. In-hospital major adverse events, including death, resuscitated cardiac arrest and cardiogenic shock, will be recorded. After discharge, all-cause death and major adverse cardiovascular events will be recorded systematically and adjudicated at 12months of follow-up., Results: The primary outcome will be the prevalence of psychoactive drugs detected by systematic screening among all patients hospitalized in an intensive cardiac care unit. The in-hospital major adverse events will be analysed according to the presence or absence of detected psychoactive drugs. Subgroup analysis stratified by initial clinical presentation and type of psychoactive drug will be performed., Conclusions: This is the first prospective multicentre study to assess the prevalence of psychoactive drugs detected by systematic screening in consecutive patients hospitalized for acute cardiovascular events., (Copyright © 2022. Published by Elsevier Masson SAS.)

For almost two decades, researchers have observed the preservation of the quantum statistical properties of bosons in a large variety of plasmonic systems. In addition, the possibility of preserving nonclassical correlations in light-matter interactions mediated by scattering among photons and plasmons stimulated the idea of the conservation of quantum statistics in plasmonic systems. It has also been assumed that similar dynamics underlie the conservation of the quantum fluctuations that define the nature of light sources. So far, plasmonic experiments have been performed in nanoscale systems in which complex multiparticle interactions are restrained. Here, we demonstrate that the quantum statistics of multiparticle systems are not always preserved in plasmonic platforms and report the observation of their modification. Moreover, we show that optical near fields provide additional scattering paths that can induce complex multiparticle interactions. Remarkably, the resulting multiparticle dynamics can, in turn, lead to the modification of the excitation mode of plasmonic systems. These observations are validated through the quantum theory of optical coherence for single- and multi-mode plasmonic systems. Our findings unveil the possibility of using multiparticle scattering to perform exquisite control of quantum plasmonic systems., (© 2021. The Author(s).)

Background: Direct oral anticoagulants (DOACs) account for an increasing proportion of prescriptions in patients with non-valvular atrial fibrillation (NVAF) in primary care. Inappropriate dosing of DOACs is a common problem, with under-dosing being a particular issue. However, conflicting results have been reported about the factors independently associated with inappropriate dosing., Aim: To describe inappropriate prescriptions of DOACs among patients in the CACAO French nationwide general practice cohort, and to identify the factors independently associated with inappropriate DOAC doses., Design and Setting: Cross-sectional baseline analysis of the CACAO French national multicentre prospective cohort of adult patients in primary care receiving an oral anticoagulant who were recruited between April and October 2014., Method: A total of 1111 patients from the CACAO cohort who received a DOAC for NVAF were included in this study. Inappropriate prescriptions of DOACs were described (inappropriate dosage, contraindications, non-indications, interactions, and non-compliance with the precautions for use). Multivariate logistic models were used to investigate factors associated with inappropriate DOAC dosing (under-dosing and over-dosing)., Results: Overall, 438 patients (39.4%) received at least one inappropriate DOAC prescription. The most common inappropriate prescription was inappropriate dosage ( n = 374, 33.7%), particularly under-dosing ( n = 348, 31.3%). Multivariate analysis revealed that factors independently associated with under-dosing were older age, prescription of apixaban or dabigatran, and a CHA2DS2-VASc score ≥2 vs. a score = 1. Factors with over-dosing were kidney failure, a HAS-BLED score ≥3, and older age., Conclusion: The appropriateness of DOAC prescribing for NVAF can be improved, especially in older patients, and in patients with kidney failure, a higher risk of ischaemic stroke, and/or a higher risk of bleeding. GPs have a key role in increasing the proportion of appropriate DOAC prescriptions via informational, educational, and/or management strategies., (© The Authors.)

Primrose syndrome is characterized by variable intellectual deficiency, behavior disorders, facial features with macrocephaly, and a progressive phenotype with hearing loss and ectopic calcifications, distal muscle wasting, and contractures. In 2014, ZBTB20 variants were identified as responsible for this syndrome. Indeed, ZBTB20 plays an important role in cognition, memory, learning processes, and has a transcription repressive effect on numerous genes. A more severe phenotype was discussed in patients with missense single nucleotide variants than in those with large deletions. Here, we report on the clinical and molecular results of 14 patients: 6 carrying ZBTB20 missense SNVs, 1 carrying an early truncating indel, and 7 carrying 3q13.31 deletions, recruited through the AnDDI-Rares network. We compared their phenotypes and reviewed the data of the literature, in order to establish more powerful phenotype-genotype correlations. All 57 patients presented mild-to-severe ID and/or a psychomotor delay. Facial features were similar with macrocephaly, prominent forehead, downslanting palpebral fissures, ptosis, and large ears. Hearing loss was far more frequent in patients with missense SNVs (p = 0.002), ectopic calcification, progressive muscular wasting, and contractures were observed only in patients with missense SNVs (p nonsignificant). Corpus callosum dysgenesis (p = 0.00004), hypothyroidism (p = 0.047), and diabetes were also more frequent in this group. However, the median age was 9.4 years in patients with deletions and truncating variant compared with 15.1 years in those with missense SNVs. Longer follow-up will be necessary to determine whether the phenotype of patients with deletions is also progressive.

Background: Underdiagnosis and undertreatment of chronic heart failure (CHF) are common in older patients, who are usually treated by general practitioners (GPs). In 2007, the French ICAGE study explored GPs' attitudes to the management of this condition in older patients., Objectives: To explore changes over time in GPs' attitudes towards the management of CHF in patients aged ≥75 and to identify barriers to optimal management., Methods: In 2015, we performed a qualitative study of 20 French GPs via semi-structured interviews and a thematic content analysis. The results were compared with the findings of a 2007 study., Results: In 2015, the perceived barriers to diagnosis were the same as in 2007. Echocardiography was still the preferred diagnostic method but the GPs relied on the cardiologist to confirm the diagnosis. Many GPs were still unaware of the different types of CHF. In contrast, they reported greater knowledge of decompensation factors and the ultrasound criteria for CHF. They also prescribed a brain natriuretic peptide assay more frequently. Angiotensin-converting enzyme inhibitors and beta blockers were more strongly perceived to be core treatments. Few GPs initiated drug treatments and optimized dosages. Although patient education was never mentioned, the importance of multidisciplinary care was emphasized., Conclusion: Our results evidenced a small recent improvement in the management of older patients with CHF. Appropriate guidelines and training for GPs, patient education and multidisciplinary collaboration might further improve the care given to this population., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

High-throughput sequencing (HTS) of human genome coding regions allows the simultaneous screen of a large number of genes, significantly improving the diagnosis of non-syndromic intellectual disabilities (ID). HTS studies permit the redefinition of the phenotypical spectrum of known disease-causing genes, escaping the clinical inclusion bias of gene-by-gene Sanger sequencing. We studied a cohort of 903 patients with ID not reminiscent of a well-known syndrome, using an ID-targeted HTS of several hundred genes and found de novo heterozygous variants in TCF4 (transcription factor 4) in eight novel patients. Piecing together the patients from this study and those from previous large-scale unbiased HTS studies, we estimated the rate of individuals with ID carrying a disease-causing TCF4 mutation to 0.7%. So far, TCF4 molecular abnormalities were known to cause a syndromic form of ID, Pitt-Hopkins syndrome (PTHS), which combines severe ID, developmental delay, absence of speech, behavioral and ventilation disorders, and a distinctive facial gestalt. Therefore, we reevaluated ten patients carrying a pathogenic or likely pathogenic variant in TCF4 (eight patients included in this study and two from our previous ID-HTS study) for PTHS criteria defined by Whalen and Marangi. A posteriori, five patients had a score highly evocative of PTHS, three were possibly consistent with this diagnosis, and two had a score below the defined PTHS threshold. In conclusion, these results highlight TCF4 as a frequent cause of moderate to profound ID and broaden the clinical spectrum associated to TCF4 mutations to nonspecific ID.

Faced with health, environmental, and socio-economic issues related to the heavy use of pesticides, diffuse phytosanitary pollution becomes a major concern shared by all the field actors. These actors, namely the farmers and territorial managers, have expressed the need to implement decision support tools for the territorial management of diffuse pollution resulting from the plant protection practices and their impacts. To meet these steadily increasing requests, a cartographic analysis approach was implemented based on GIS which allows the spatialization of the diffuse pollution impacts related to plant protection practices on the Etang de l'Or catchment area in the South of France. Risk mapping represents a support-decision tool that enables the different field actors to identify and locate vulnerable areas, so as to determine action plans and agri-environmental measures depending on the context of the natural environment. This work shows that mapping is helpful for managing risks related to the use of pesticides in agriculture by employing indicators of pressure (TFI) and risk on the applicator's health (IRSA) and on the environment (IRTE). These indicators were designed to assess the impact of plant protection practices at various spatial scales (field, farm, etc.). The cartographic analysis of risks related to plant protection practices shows that diffuse pollution is unequally located in the North (known for its abundant garrigues and vineyards) and in the South of the Etang de l'Or catchment area (the Mauguio-Lunel agricultural plain known for its diversified cropping systems). This spatial inequity is essentially related to land use and agricultural production system. Indeed, the agricultural lands cover about 60% of the total catchment area. Consequently, this cartographic analysis helps the territorial actors with the implementation of strategies for managing risks of diffuse pollution related to pesticides use in agriculture, based on environmental and socio-economic issues and the characteristics of the natural environment.