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Objective:Central-line–associated bloodstream infections (CLABSIs) are associated with significant morbidity among pediatric oncology-hematology patients, and risk factors remain largely unknown in the setting of hospital at home (HAH). Children in HAH receive intensive treatment (eg, chemotherapy and parenteral nutrition), with frequent central-line handling; thus, they may be at higher risk for CLABSI.Methods:We conducted a monocentric retrospective study of patients with a central line included in our HAH program from January 1 to December 31, 2016. HAH patient characteristics for children developing CLABSIs were compared to those who did not, based on blood cultures positive for infection and clinical data of all patients included.Results:Overall, 492 HAH stays were analyzed, with 144 patients. The overall CLABSI rate in these patients was 2.6 per 1,000 central-line days. Children who developed CLABSIs were younger (median age, 2.5 vs 8.8 years; P < .001), suffered more from hematological pathologies (malignant or nonmalignant, 75% vs 52%; P = .02), and had more frequently undergone hematopoietic stem-cell transplantation (30.8% vs 6.5%; P = .01). In addition, these patients often had a tunneled externalized catheter as the central line and were more frequently given parenteral nutrition at home (46% vs 8%; P < .001).Conclusions:CLABSI rates for children in HAH were more similar to those of inpatients than to rates previously reported for ambulatory patients. The factors associated with infection identified herein should be further validated in multicentric studies and considered to improve HAH practices, parallel to prevention measures used in the inpatient setting.

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Acute kidney injury (AKI) is a major cause of mortality in tumor lysis syndrome. The biochemical parameters and kinetics of tumor lysis syndrome remain poorly described. Particularly, whether blood serum phosphate variations may help in the identification and management of patients who will eventually develop AKI remains to be studied.In this retrospective study, we included patients with tumor lysis syndrome episodes without AKI at diagnosis, and analyzed serum phosphate kinetic, clinical and tumor lysis syndrome biochemical variables to identify factors associated with AKI onset, and determine threshold values of phosphatemia associated with AKI development.One hundred thirty tumor lysis syndrome episodes occurred in 120 patients during an 11-year period at the University Hospital of Angers. AKI developed in 56 tumor lysis syndrome episodes. In multivariable analysis, among the analyzed factors, only an increase in serum phosphate levels (before AKI diagnosis), exposure to platinum salts and an increase in LDH levels were associated with AKI development. Before AKI onset, a serum phosphate cut-off of 2.1 mmol/L was not effective in predicting AKI development (sensitivity 48%, specificity 84%, area under the receiver operating characteristic curve (AUC) 0.63 [0.52-0.74]). No other biochemical parameters were effective to better predict AKI occurrence.This work suggests that increases in serum phosphate and LDH appear to be early and reliable biomarkers of AKI in tumor lysis syndrome. No valuable threshold value of serum phosphate was found to effectively predict AKI. This work is the basis for further prospective controlled studies on phosphate monitoring and phosphate lowering therapies to prevent AKI during tumor lysis syndrome.

Modal shift in public transport as a consequence of a disruption on a line has in some cases unforeseen consequences such as an increase in congestion in the rest of the network. How information is provided to users and their behavior plays a central role in such configurations. We introduce here a simple and stylised agent-based model aimed at understanding the impact of behavioural parameters on modal shift. The model is applied on a case study based on a stated preference survey for a segment of Paris suburban train network. We systematically explore the parameter space and show non-trivial patterns of congestion for some values of discrete choice parameters linked to perceived wait time and congestion. We also apply a genetic optimisation algorithm to the model to search for optimal compromises between congestion in different modes., Comment: 8 pages, 4 figures

Phytoplankton-bacteria interactions are governed by the transformation of algal-derived organic matter, exchange of metabolites and infochemicals. However, the assembly of the bacterial community within the phycosphere is not well understood. In this study, we performed experiments to tease apart the role of species-specific exometabolites, bacterial/bacterial interactions and algal/bacterial interactions in shaping bacterial community within the phycophere. Twelve bacterial isolates, representative of the main members of the phycosphere microbiome were selected and exposed to phytoplankton extracellular fractions (PEF) from Alexandrium minutum, Prymnesium parvum and Tisochrysis lutea. While all bacterial isolates were able to grow individually on the different PEF, the bacterial community analysis indicated that some species were selected and others were not when grown in a synthetic community (SynCom). In addition, we compared the SynCom assembly in the absence or presence of the harmful algal cells. If PEF, irrespective of the producing alga, allowed the growth of copiotrophic strains, we found that exometabolites of the two different species led to distinct SynCom composition and that the presence of algal cells also influenced the bacterial assemblage. Overall, our results support the assertion that algal exudates and the presence of algae are the main factors driving the composition of the bacterial community.

Bone lesions are rarely reported in Hairy Cell Leukemia (HCL). We report two BRAFV600E mutated HCL patients presented bone lesions at foreground, poor bone marrow involvement and the important role 18F-FDG PET/CT played in their management. We discuss the crucial role that 18F-FDG PET/CT could play in HCL routine practice.

Supplementary data

We use Google Scholar to examine the niche of housing research within migration studies through a broad range of documents. The contribution of this meta-analysis is threefold. Firstly, we illustrate the association of keywords across the corpus of literature related to migration and housing and map the growth of migration literature since the 1960s. Secondly, we highlight key bridging documents using network measures. Finally, we estimate the distance in reading time between documents.

L’article porte sur la manière dont les relations science-industrie déterminent la production de savoirs et les formes de collaboration et d’organisation scientifiques contemporaines à partir de l’institutionnalisation manquée d’une spécialité émergente, à savoir la biologie synthétique. En mobilisant la notion de cadrage industriel et à partir de l’analyse symétrique de deux façons de cadrer la biologie synthétique en France, nous montrons l’importance des dimensions cognitives et des régulations industrielles dans la construction des collaborations entre science et industrie là où la littérature a surtout insisté sur la montée des régulations marchandes. Après une sociogenèse des cadrages industriels du Genopole d’Évry et du Toulouse Biotechnology Institute permettant de mettre au jour deux configurations associant science et industrie, l’article montre comment ces cadrages déterminent l’appropriation et la délimitation différenciées de la biologie synthétique. La stabilisation de la biologie synthétique comme ensemble de technologies au détriment d’une biologie synthétique académique est analysée comme le produit de résultats expérimentaux concernant le développement d’applications industrielles, l’inscription de la biologie synthétique dans la trajectoire historique des sciences pour l’ingénieur et l’accès aux ressources publiques en matière de recherche. This article analyses how science-industry relationships determine the production of knowledge forms of contemporary scientific collaboration and organization based on the failed institutionalization of an emerging specialty, namely synthetic biology. By mobilizing the notion of industrial framing and using the symmetrical analysis of two ways of framing synthetic biology in France, we show the importance of cognitive dimensions and industrial regulations in the construction of collaborations between science and industry — whereas the literature has essentially focused on the rise of market regulations. After a socio-genesis of the industrial framing of Genopole and the Toulouse Biotechnology Institute allowing us to reveal two ways of combining science and industry, the article shows how these framing determine the different appropriation and delimitation of synthetic biology. The stabilization of synthetic biology as a chain of knowledge production to the detriment of an academic speciality is described as the combination of experimental results concerning the development of industrial applications, the inclusion of synthetic biology in the historical trajectory of institutionalized engineering and access to public resources.

The detection of slope change points in wind curves depends on linear curve-fitting. Hall and Titterington's algorithm based on smooth- ing is adapted and compared to a Bayesian method of curve-fitting. After prior spline smoothing of the data, the algorithms are tested and the er- rors between the split-linear fitted wind and the real one are estimated. In our case, the adaptation of the edge-preserving smoothing algorithm gives the same good performance as automatic Bayesian curve-fitting based on a Monte Carlo Markov chain algorithm yet saves computation time. This study is aimed at the improvement of the aircraft autopilot concep- tion process. The autopilot allows landings in bad weather conditions and must guarantee passengers safety, touchdown comfort, and precision. We study in par- ticular the influence of wind during automatic landing. We focus on the effect of the linear wind components in the last 30 seconds to show that they are a decisive factor in touchdown precision. This is achieved by comparing simulated landings with either a real wind or its piecewise linear approximation. This has led us to develop a method of split-linear fitting based on slope change detection adapted to our data. This method is similar to those proposed by Jones (1998) which aim at predicting the influence of discrete gusts on linear systems. Slope change detection is associated with edge and peak detection. Two kinds of method can be adapted : a classic one, based on smoothing and a Bayesian one based on Monte Carlo Markov Chains. Hall and Titterington (1992) pro- posed an edge-preserving smoothing algorithm. It is based on edge detection by comparisons of three smoothings. The aim of this method is to compute, for each given point, three smoothed estimates of the function, based on the data to the right, to the left and on both sides of the point. Each discontinuity is asso- ciated with a local maximum of the difference between the three fits. Wu and Chu (1993) took this algorithm and modified it using kernel smoothing instead

Cet article se propose d’interroger la réduction du processus de molécularisation du vivant à sa dimension informationnelle à partir des années 1970-1980 en réintégrant une ontologie chimique du vivant qui se caractérise par la centralité des questions de production et une grande proximité avec l’industrie. La mise en visibilité et la caractérisation d’une molécularisation chimique du vivant sont enquêtées à partir de la naissance et la stabilisation d’un domaine scientifique peu connu : l’ingénierie métabolique. Pour cela, nous nous appuyons sur un travail associant analyse scientométrique d’un corpus de 6 288 articles scientifiques, traitement d’archives d’un centre de recherche ainsi qu’une série d’entretiens semi-directifs avec plusieurs figures fondatrices de l’ingénierie métabolique.

The aim of our study was to identify and evaluate the complications related to hyaluronic acid during the COVID-19 pandemic.Twelve dermatologists participated in this study. A cohort and a non-cohort follow-up were ensured.(1) Cohort follow-up: 1041 patients. 8% had a COVID-19 infection, 27% had received COVID-19 vaccination. 2% had immediate side effects (edema, erythema, bruising). 0.5% had delayed side effects (two inflammatory nodules, one nodule without inflammation, one edema). None of these side effects occurred in the context of infection or COVID-19 vaccinations. (2) Non-cohort follow-up: 7900 syringes used. Two early side effects (inflammatory edema) were reported, of which one occurred 15 days after vaccination. Two cases of delayed side effects such as inflammation on the injected area and inflammatory nodules occurred of which one was in the context of vaccination and one during COVID-19 infection. We estimate the frequency of complications possibly attributable to the disease or to the COVID vaccination to be 0.06% in our population.Complications of HA injections in the context of COVID-19 disease or vaccination appear to be very rare but the frequency could be underestimated because of the low rate of vaccination/infection in our population. Our study shows a very good tolerance of hyaluronic acid injections during the COVID-19 pandemic.

Purpose. Some high-risk medulloblastomas (HR-MB) do not respond to induction chemotherapy, with either post-induction stable (SD) or progressive disease (PD). To date, there is no consensus regarding their optimal management. Methods. A retrospective, multicentre study of non-responder HR-MB patients treated according to the PNET HR+5 protocol (NCT00936156) between 01/01/2009 and 31/12/2018. After two courses of etoposide and carboplatin induction chemotherapy, patients with SD or PD were analyzed. Based on the clinician’s decision, the PNET HR+5 protocol was either pursued with tandem high-dose chemotherapy (HDCT) and craniospinal irradiation (CSI) (continuation group) or it was modified (switched group). Results. Forty-nine patients were identified. After induction, 37 patients had SD and 12 had PD. The outcomes were significantly better for the SD group: the 5-y PFS and OS were 52% (95% confidence interval [95% CI] 35-67) and 70% (95% CI 51-83), respectively, in the SD group and 17% (95% CI 3-41) and 13% (95% CI 1-40), respectively, in the PD group (p < 0.0001). The PNET HR+5 strategy was pursued for 3 patients in the PD group, of whom only one survived. In the SD group, it was pursued for 24 patients. The 5-y PFS and the OS were 78% (95% CI 54-90) in the continuation group and 0% and 56% (95% CI 23-79), respectively, in the switched group. In the SD group, multivariate analysis revealed that MYC amplification, molecular group 3, and a switched strategy were independent prognostic factors for progression. Conclusion. Patients with post-induction SD may benefit from HDCT and CSI, whereas improvement of the way patients with early PD are treated will require new therapeutic approaches.

The role of ribosome biogenesis in erythroid development is supported by the recognition of erythroid defects in ribosomopathies in both Diamond-Blackfan anemia and 5q− syndrome. Whether ribosome biogenesis exerts a regulatory function on normal erythroid development is still unknown. In the present study, a detailed characterization of ribosome biogenesis dynamics during human and murine erythropoiesis showed that ribosome biogenesis is abruptly interrupted by the decline in ribosomal DNA transcription and the collapse of ribosomal protein neosynthesis. Its premature arrest by the RNA Pol I inhibitor CX-5461 targeted the proliferation of immature erythroblasts. p53 was activated spontaneously or in response to CX-5461, concomitant to ribosome biogenesis arrest, and drove a transcriptional program in which genes involved in cell cycle–arrested, negative regulation of apoptosis, and DNA damage response were upregulated. RNA Pol I transcriptional stress resulted in nucleolar disruption and activation of the ATR-CHK1-p53 pathway. Our results imply that the timing of ribosome biogenesis extinction and p53 activation is crucial for erythroid development. In ribosomopathies in which ribosome availability is altered by unbalanced production of ribosomal proteins, the threshold downregulation of ribosome biogenesis could be prematurely reached and, together with pathological p53 activation, prevents a normal expansion of erythroid progenitors.

Background Platelet‐derived growth factor is a major regulator of the vascular remodeling associated with pulmonary arterial hypertension. We previously showed that protein widely 1 (PW1 + ) vascular progenitor cells participate in early vessel neomuscularization during experimental pulmonary hypertension (PH) and we addressed the role of the platelet‐derived growth factor receptor type α (PDGFRα) pathway in progenitor cell‐dependent vascular remodeling and in PH development. Methods and Results Remodeled pulmonary arteries from patients with idiopathic pulmonary arterial hypertension showed an increased number of perivascular and vascular PW1 + cells expressing PDGFRα. PW1 nLacZ reporter mice were used to follow the fate of pulmonary PW1 + progenitor cells in a model of chronic hypoxia–induced PH development. Under chronic hypoxia, PDGFRα inhibition prevented the increase in PW1 + progenitor cell proliferation and differentiation into vascular smooth muscle cells and reduced pulmonary vessel neomuscularization, but did not prevent an increased right ventricular systolic pressure or the development of right ventricular hypertrophy. Conversely, constitutive PDGFRα activation led to neomuscularization via PW1 + progenitor cell differentiation into new smooth muscle cells and to PH development in male mice without fibrosis. In vitro, PW1 + progenitor cell proliferation, but not differentiation, was dependent on PDGFRα activity. Conclusions These results demonstrate a major role of PDGFRα signaling in progenitor cell–dependent lung vessel neomuscularization and vascular remodeling contributing to PH development, including in idiopathic pulmonary arterial hypertension patients. Our findings suggest that PDGFRα blockers may offer a therapeutic add‐on strategy to combine with current pulmonary arterial hypertension treatments to reduce vascular remodeling. Furthermore, our study highlights constitutive PDGFRα activation as a novel experimental PH model.

Dans les metropoles contemporaines, les activites logistiques (entrepots, transport de marchandises et livraisons) rassemblent desormais plus d’ouvriers que l’industrie manufacturiere. A partir de ce constat, l’objectif de l’article est d’explorer, pour le cas de l’Ile-de-France et par une analyse cartographique, les consequences spatiales de cette mutation sectorielle majeure pour le groupe ouvrier. Dans ce but, nous comparons les lieux de travail et les lieux de residence (a l’echelle communale) des ouvriers de la logistique et de l’industrie en 2012-2013 a partir des donnees des Recensements de la population et analysons les caracteristiques sociodemographiques de ces deux espaces. L’article montre ainsi que le developpement des emplois ouvriers logistiques et leur localisation dans des zones logistiques de plus en plus peripheriques dessinent en grande couronne des espaces ouvriers fragmentes entre lieux de travail et de residence. Les communes populaires de la banlieue industrielle historique restent tout de meme les espaces ou se concentrent le plus nettement a la fois les emplois et les logements des ouvriers contemporains, qu’ils travaillent dans la logistique ou dans l’industrie.

We present two independent cases of syndromic thrombocytopenia with multiple malformations, microcephaly, learning difficulties, dysmorphism and other features. Exome sequencing identified two novel de novo heterozygous variants in these patients, c.35G>T p.(Gly12Val) and c.178G>C p.(Gly60Arg), in the RAP1B gene (NM_001010942.2). These variants have not been described previously as germline variants, however functional studies in literature strongly suggest a clinical implication of these two activating hot spot positions. We hypothesize that pathogenic missense variants in the RAP1B gene cause congenital syndromic thrombocytopenia with a spectrum of associated malformations and dysmorphism, possibly through a gain of function mechanism.

Intra-tumor heterogeneity portends poor outcome in many cancers. In AML, a higher number of drivers worsens prognosis. The Shannon Index is a robust metric of clonal heterogeneity that accounts for the number of clones, but also their relative abundance. We show that a Shannon Index can be estimated from bulk sequencing, which is correlated (ρ = 0.76) with clonal diversity from single-colony genotyping. In a discovery cohort of 292 patients with sequencing of 43 genes, a higher number of drivers (HR = 1.18, P = 0.028) and a lower Shannon Index (HR = 0.68, P = 0.048), the latter reflecting clonal dominance, are independently associated with worse OS independently of European LeukemiaNet 2017 risk. These findings are validated in an independent cohort of 1184 patients with 111-gene sequencing (number of drivers HR = 1.16, P = 1 × 10−5, Shannon Index HR = 0.81, P = 0.007). By re-interrogating paired diagnosis/relapse exomes from 50 cytogenetically normal AMLs, we find clonal dominance at diagnosis to be correlated with the gain of a significantly higher number of mutations at relapse (P = 6 × 10−6), hence with clonal sweeping. Our results suggest that clonal dominance at diagnosis is associated with the presence of a leukemic phenotype allowing rapid expansion of new clones and driving relapse after chemotherapy.

Purpose From the perspective of two groups of governance actors, this paper aims to understand how internal audit (IA) achieves and consolidates organizational significance. Design/methodology/approach Interviews were conducted with audit committee chairs and chief audit executives from multinational corporations, and the participating corporations’ registration documents were analyzed. Findings The data indicate that IA achieves and consolidates organizational significance by activating the IA effectiveness “building blocks” (Lenz et al., 2014) all together so as to generate organizational learning and positive change. New IA effectiveness drivers also emerged from the field. Research limitations/implications This research contributes to the IA literature by establishing a connection, through the IA impact on organizational learning, between the constructs of IA effectiveness and organizational significance. It also contributes to the IA literature by identifying new drivers and illustrating the complementarity and interconnections between the IA effectiveness building blocks. Practical implications This paper encourages internal auditors to keep their eyes on the prize (i.e. organizational significance) instead of simply being focused on the mean (i.e IA effectiveness), in order to fight stakeholder disappointment. Originality/value The paper proposes a conceptual model of IA organizational significance and gives key insights for setting up effective IA to stimulate organizational learning and fostering positive change in the whole organization.

Within the framework of the Rhône Sediment Observatory, monthly time-integrated samples have been collected by Particle Traps in the last decade to monitor particulate contaminants in the Rhône River and its main tributaries. In this watershed with a contrasted hydrology, a clustering approach is used to classify the samples according to the main hydrological events. This approach has been applied to riverine particulate organic radiocarbon signatures (Δ

Introduction Mitotane (o, p′-DDD) is a molecule that was developed many years ago for adrenal cortical carcinoma, but no suitable pediatric dosage form is available for administration to young children. Mitotane requires therapeutic drug monitoring because of its long half-life and difficulty in stabilizing plasma concentrations. Furthermore, Mitotane is a highly lipophilic drug that requires concurrent lipid administration. Case report We present the case of a 3-year-old girl who was diagnosed with metastatic adrenal cortical carcinoma. Due to the difficulty in administering the tablets and the non-stabilized mitotane dosages, a nasogastric tube was inserted. An administration protocol based on dispersing the tablets in whole milk was established by the pharmacy team. This led to the stabilization of the disease for at least 1.5 years. Management and outcome Mitotanemia is difficult to stabilize even when treatment is administered orally. To maintain biological efficacy, we propose an easily reproducible protocol. The efficacy was stabilized at a dosage of 1500 mg per day. Mitotanemia fluctuated between 14 mg/mL, and 20 mg/mL. The implementation of this protocol prevented treatment discontinuation. Discussion The administration of narrow therapeutic range drugs via a nasogastric tube is a challenge for healthcare teams, particularly in pediatric patients. Based on the findings of this clinical case, clinicians should consider future use of this protocol. The use of whole milk as a vehicle for mitotane is a simple, effective, and reproducible method to administer the drug to pediatric patients and can be used for other similar cases.

Firm clusters are seen as having a positive effect on innovations, what can be interpreted as economies of scale or knowledge spillovers. The processes underlying the success of these clusters remain difficult to isolate. We propose in this paper a stylised agent-based model to test the role of geographical proximity and informal knowledge exchanges between firms on the emergence of innovations. The model is run on synthetic firm clusters. Sensitivity analysis and systematic model exploration unveil a strong impact of interaction distance on innovations, with a qualitative shift when spatial interactions are more intense. Model bi-objective optimisation shows a compromise between innovation and product diversity, suggesting trade-offs for clusters in practice. This model provides thus a first basis to systematically explore the interplay between firm cluster geography and innovation, from an evolutionary perspective.

We observe that a large part of the volume of a hyperbolic polyhedron is taken by a tubular neighbourhood of its boundary, and use this to give a new proof for the finiteness of arithmetic maximal reflection groups following a recent work with M. Fraczyk and S. Hurtado. We also study in more depth the case of polygons in the hyperbolic plane.

In a previous work (Alvarez Laguna et al 2022 Phys. Plasmas 29 083507), we have developed a non-linear moment model for electrons that self-consistently captures non-Maxwellian electron energy distribution function effects. The model does not rely in the local approximation and the transport coefficients are calculated by expanding the distribution function into Hermite polynomials and by taking moments of the Boltzmann equation, including the collision operator for elastic and inelastic collisions with arbitrary cross sections. This model captures the classical Fick’s, Fourier’s, and Ohm’s law as well as Soret, Dufour, and Peltier effects. In addition, novel non-local transport phenomena appear as a result of spatial gradients of the kurtosis of the distribution function. In this paper, we discuss on the transport effects by analyzing two collisional models: constant collision frequency and constant cross section. We estimate the order of magnitude of the transport processes in non-equilibrium electrons by analyzing the Langmuir probe measurements of a low-pressure argon inductively-coupled discharge. The results show that, under these conditions, the transport produced by the spatial gradients in the kurtosis of the distribution function produces a heat-flux contribution that is of the same order of magnitude as the Fourier and Dufour’s effects. These transport effects are beyond the local field or the electron gradient expansions, commonly used in the low-temperature plasma modeling.

International audience; An ion chromatography system employing a low-cost three-dimensional printed absorbance detector for indirect ultraviolet detection towards portable phosphate analysis of environmental and industrial waters has been developed. The optical detection cell was fabricated using stereolithography three-dimensional print- ing of nanocomposite material. Chromatographic analysis and detection of phos- phate were carried out using a CS5A 4 × 250 mm analytical column with indirect ultraviolet detection using a 255 nm light-emitting diode. Isocratic elution using a 0.6 mM potassium phthalate eluent combined with 1.44 mM sodium bicarbon- ate was employed at a flow rate of 0.75 ml/min. A linear calibration range of 0.5 to 30 mg/L PO43− applicable to environmental and wastewater analysis was achieved. For retention time and peak area repeatability, relative standard devi- ation values were 0.68% and 4.09%, respectively. Environmental and wastewater samples were analyzed with the optimized ion chromatography platform and the results were compared to values obtained by an accredited ion chromatograph. For the analysis of environmental samples, relative errors of

Este artículo contiene 30 páginas, 14 figuras., The Mediterranean community represented in this paper is the result of more than 30 years of EU and nationally funded coordination, which has led to key contributions in science concepts and operational initiatives. Together with the establishment of operational services, the community has coordinated with universities, research centers, research infrastructures and private companies to implement advanced multi-platform and integrated observing and forecasting systems that facilitate the advancement of operational services, scientific achievements and mission-oriented innovation. Thus, the community can respond to societal challenges and stakeholders needs, developing a variety of fit-for-purpose services such as the Copernicus Marine Service. The combination of state-of-the-art observations and forecasting provides new opportunities for downstreamservices in response to the needs of the heavily populatedMediterranean coastal areas and to climate change. The challenge over the next decade is to sustain ocean observations within the research community, to monitor the variability at small scales, e.g., the mesoscale/submesoscale, to resolve the sub-basin/seasonal and inter-annual variability in the circulation, and thus establish the decadal variability, understand and correct the model-associated biases and to enhance model-data integration and ensemble forecasting for uncertainty estimation. Better knowledge and understanding of the level ofMediterranean variability will enable a subsequent evaluation of the impacts and mitigation of the effect of human activities and climate change on the biodiversity and the ecosystem, which will support environmental assessments and decisions. Further challenges include extending the science-based added-value products into societal relevant downstream services and engaging with communities to build initiatives that will contribute to the 2030 Agenda and more specifically to SDG14 and the UN’s Decade of Ocean Science for sustainable development, by this contributing to bridge the science-policy gap. The Mediterranean observing and forecasting capacity was built on the basis of community best practices in monitoring and modeling, and can serve as a basis for the development of an integrated global ocean observing system.

The objective was to evaluate health care providers' (HCP) adherence to and efficacy of varicella post-exposure prophylaxis (PEP) recommendations. It was an observational, prospective, multicenter study set in Ile-de-France, France.All children under 18 with a cancer diagnosis, currently or within 3months of receiving cancer treatment, regardless of varicella zoster virus (VZV) serostatus or previous personal history of varicella, were eligible. Study participants with significant exposure were reviewed prospectively for PEP indications. Main outcome measures were the percentage of exposure situations for which HCP were guideline-compliant, the proportion of available VZV serostatuses and the incidence of breakthrough varicella after different PEP approaches.A total of 51 patients from 15 centers were enrolled after 52 exposure episodes. Median age at exposure was 5 years (range, 1-15). Exposure within the household led to 38% of episodes. Prophylactic treatment consisted in specific anti-VZV immunoglobulins (V-ZIG) (n=19) or in oral aciclovir (n=15). No prophylactic treatment was given for 18 patients (in compliance, n=16). In compliance with guidelines, 17 patients received V-ZIG, 11 did not develop varicella (65%, [95% CI, 39-90%]); 15 received aciclovir, 13 did not develop varicella (87%, [95% CI, 67-100%]). Breakthrough varicella occurred in 11 patients, with simple clinical course in all cases; in 8/47 (17%) episodes when PEP was guideline-compliant versus 3/5 (60%) when not.Recommendations have been respected and are efficient. PEP needs to be standardized and a study carried out to define the optimal approach. Anti-VZV immunization of seronegative family members should be encouraged.

The complexity of interactions between networks and territories has been widely acknowledged empirically, in particular through the existence of circular causal relations in their co-development, that can be understood as a co-evolution. This contribution aims at investigating models that endogenize this co-evolution, in the particular case of cities and transportation networks. We introduce a family of models of co-evolution for systems of cities at the macroscopic scale. Interactions between cities are the main driver of population growth rates, capturing a network effect at the first order (direct interactions). Network growth follows a demand-induced thresholded growth scheme, that can occur at the global level or locally. The exploration of the model on synthetic systems of cities shows the ability of the model to capture co-evolutive patterns. We apply the model on the French system of cities, with population data spanning 1831-1999 and a dynamical railway network (1850-2000). The model is calibrated on successive time-windows, assuming local temporal stationarity. We extract therein indirect knowledge on underlying processes and find that the prediction for city populations are in some cases improved in comparison to a static model.

Phthalate esters, mainly di-ethylhexylphthalate (DEHP), represent a class of chemicals primarily used as plasticizers for polyvinyl chloride in a wide range of domestic and industrial applications. These phthalate esters are low-toxicity environmental contaminants. To address these drawbacks, POLYSORB® ID 37, a blend of diesters obtained from esterification of isosorbide with plant-based fatty acids, was developed. The company can now offer PVC manufacturers a new product which competes with phthalates and other such chemicals. The market for plasticizers is very important, and ROQUETTE intends to provide a more sustainable and safer product. Isosorbide diester is bio-based (made from glucose and vegetable fatty acids). This plasticizer is registered in REACH regulation for high volumes (>1000 T/year). Risk assessment was obtained by conducting a wide range of biodegradability and toxicological protocols, using rodent models, according to established guidelines. Overall, all of the toxicological and biodegradability studies demonstrated that POLYSORB® ID 37 is nontoxic to mammalian life and is readily biodegradable.

Germline DDX41 mutations are involved in familial myelodysplastic syndromes (MDSs) and acute myeloid leukemias (AMLs). We analyzed the prevalence and characteristics of DDX41-related myeloid malignancies in an unselected cohort of 1385 patients with MDS or AML. Using targeted next-generation sequencing, we identified 28 different germline DDX41 variants in 43 unrelated patients, which we classified as causal (n = 21) or unknown significance (n = 7) variants. We focused on the 33 patients having causal variants, representing 2.4% of our cohort. The median age was 69 years; most patients were men (79%). Only 9 patients (27%) had a family history of hematological malignancy, and 15 (46%) had a personal history of cytopenia years before MDS/AML diagnosis. Most patients had a normal karyotype (85%), and the most frequent somatic alteration was a second DDX41 mutation (79%). High-risk DDX41 MDS/AML patients treated with intensive chemotherapy (n = 9) or azacitidine (n = 11) had an overall response rate of 100% or 73%, respectively, with a median overall survival of 5.2 years. Our study highlights that germline DDX41 mutations are relatively common in adult MDS/AML, often without known family history, arguing for systematic screening. Salient features of DDX41-related myeloid malignancies include male preponderance, frequent preexisting cytopenia, additional somatic DDX41 mutation, and relatively good outcome.