Lightweight certificateless and provably-secure signcryptosystem for the internet of things

International audienceIn this paper, we propose an elliptic curve-based signcryption scheme derived from the standardized signature KCDSA (Korean Certificate-based Digital Signature Algorithm) in the context of the Internet of Things. Our solution has several advantages. First, the scheme is provably secure in the random oracle model. Second, it provides the following security properties: outsider/insider confidentiality and unforgeability; non-repudiation and public verifiability, while being efficient in terms of communication and computation costs. Third, the scheme offers the certificateless feature, so certificates are not needed to verify the user's public keys. For illustration, we conducted experimental evaluation based on a sensor Wismote platform and compared the performance of the proposed scheme to concurrent scheme

Contribution à l'étude des ponts à dalles pleines en béton précontraint renforcé de fibres métalliques

Suite à la destruction du Concorde Viaduc à Montréal en 2006, le Ministère des Transports du Québec (MTQ) a exigé une armature de cisaillement supplémentaire même s'il n'est pas nécessaire dans les calculs. L'objectif principal de ce projet de recherche est de développer une dalle structurale précontrainte sans armature passive et d'étudier la possibilité de remplacer l'armature transversale minimale de cisaillement exigée par le Ministère des Transports du Québec (MTQ) par des fibres métalliques pour une meilleure ductilité tout en gardant le même niveau de fiabilité structurale Le projet de recherche consiste à étudier le comportement en cisaillement de dalles en BFM. Il vise à examiner l'influence du renforcement par fibres métalliques sur la capacité et la ductilité de dalles en béton armé ou précontraint. L'étude expérimentale de ce projet de recherche se divise en trois parties : i) des essais de caractérisation "des matériaux, ii) des essais sur la zone d'ancrage, iii) des essais de cisaillement sur dalles structurales qui visent à étudier le comportement à l'effort tranchant des dalles en béton précontraint renforcé de fibres métalliques

Empéripolèse des cellules de lymphomes humains Ramos par les fibroblastes

Le fichier vidéo en format .avi accompagne mon document et correspond à l'annexe II. C'est une vidéomicroscopie dont la légende est mise en annexe II.Les fibroblastes (Fbs) constituent le type cellulaire dominant du stroma tumoral. Une vision "cafocentrique" du microenvironnement tumoral (MET) soutient que les interactions dynamiques et réciproques entre les cellules tumorales et les "cancer-associated fibroblasts" (CAFs) favoriseraient le potentiel métastasique des cellules tumorales. Notre principale hypothèse soutient qu'une interaction physique directe entre les cellules tumorales et les CAFs au sein du stroma tumoral est non seulement possible grâce au couple α4β1/VCAM-1 mais qu'elle pourrait éventuellement constituer une cible thérapeutique de choix. Grâce à la cytofluorométrie et aux anticorps bloquants, nous avons montré que des cellules de lymphome humain Ramos sont capables d'interagir avec les Fbs, que cette interaction est modulable et qu'elle implique le couple α4β1/VCAM-1. Une augmentation dose-dépendante de cette interaction ainsi que du niveau d'expression de VCAM-1 après une stimulation préalable des Fbs par le TNF-α ont été observés. Ce résultat a été confirmé par la surexpression de VCAM-1 par transfection. Des analyses par microscopie confocale ont révélé que les Ramos sont internalisés dans le cytoplasme des Fbs, phénomène connu sous le nom d'empéripolèse et qui correspond en partie à de la migration transcellulaire. Une colocalisation de la sous-unité α4 de α4β1 et de VCAM-1 à la jonction d'adhésion des Ramos aux Fbs ainsi que l'implication de la vimentine au niveau des cônes de migration ont été observées. La vidéomicroscopie a confirmé ce processus cellulaire actif. Finalement, un modèle mimétique de billes fluorescentes de polystyrène tapissées de α4β1 a confirmé les précédents résultats. Cette étude révèle que les Ramos peuvent interagir puis transmigrer à travers les Fbs grâce au couple α4β1/VCAM-1 de façon modulable. Tel que stipulé dans l'hypothèse du "Seed and Soil", nos résultats supportent l'hypothèse d'un adressage cellulaire et tissulaire dans la dissémination métastasique des cellules tumorales qui s'implanteraient préférentiellement là où l'expression de VCAM-1 a été induite. Le couple α4β1/VCAM-1 pourrait servir de cible thérapeutique de choix dans le développement de nouveaux antagonistes anticancéreux.Fibroblasts (Fbs) often represent the majority of stromal cells within tumors. A “cafocentric” view of the tumor microenvironment (MET) hypothesizes that the dynamic and reciprocal interactions between tumor cells and cancer-associated fibroblasts (CAFs) may enhance the metastatic potency of tumor cells. Very few studies investigated a physical interaction between Fbs and tumor cells within the tumor stroma. Using flow cytometry and blocking antibodies, we demonstrated that a human lymphoma cell line Ramos could interact with Fbs through the couple α4β1/VCAM-1. We observed a dose-dependent increased interaction after tumor necrosis factor-α (TNF-α) stimulation which correlated with increased VCAM-1 expression. A similar observation was made after VCAM-1 overexpression by transfection. Further investigations by confocal microscopy revealed the engulfment of Ramos into the cytoplasm of Fbs, a process called emperipolesis which mostly corresponds to transcellular migration and involves the clustering of the α4 sub-unit and VCAM-1 and the involvement of vimentin intermediate filaments at the transmigration cups. We visualized this cell-in-cell penetration by real time-lapse video-microscopy, which confirmed an active cellular process. Finally, we used α4β1 polystyrene coated-beads as a mimetic model to further confirm the precedent results. Our results showed that Ramos lymphoma cells can interact with and further transmigrate through Fbs by an active cellular process, the emperipolesis which involves the couple of receptors α4β1/VCAM-1. This crosstalk between Fbs and tumor cells through emperipolesis may modulate tumor cells escape from the primary tumor and support the "seed and soil" hypothesis as well as a possible involvement in tumor drug resistance. This fibroblastic permeability can be modulated by inflammation and the CAFs may react as endothelial cells and should be considered as a future target in the MET. Tumor cells may selectively search for new metastatic niches where VCAM-1 expression was already induced. Our results strengthen the growing idea that Fbs and tumor cell integrins may serve as suitable targets in the development of antagonist-based cancer therapy

Adhesion and transcellular migration of neutrophils and B lymphocytes on fibroblasts

During tissue inflammation, infiltrated leukocytes may have physical contacts with fibroblasts. We observed that neutrophils and B lymphocytes adhered in a larger proportion than T cells on cultured fibroblasts. Microscopy showed that adhesion was also characterized by leukocyte engulfment by the fibroblasts. In migration assays, only neutrophils and B lymphocytes were selectively able to migrate through a fibroblast barrier. Adhesion and migration were increased by stimulation with tumor necrosis factor-alpha (TNF-alpha) and phorbol-12-myristate-13-acetate (PMA). Antibodies against ICAM-1/beta2 integrin blocked the interaction of neutrophils to fibroblasts. For B lymphocytes the couple VCAM-1/alpha4 integrin was also involved in this interaction. Human skin fibroblasts presented similar adhesion characteristics as rat cardiac fibroblasts. By measuring the distance between the border of migration holes and cadherin-positive adherens junctions, more than 65% of the holes correspond to the transcellular route over the paracellular route. Furthermore, vimentin staining revealed that the migration holes were highly nested by intermediate filaments in accordance with the transcellular route. Our results demonstrated that engulfment of neutrophils and B lymphocytes by fibroblasts resulted in selective passage by a transcellular route.This work was supported by grants from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Counci

Secure P2P Data Storage and Maintenance

P2P data storage requires strong reliability and security assurances. Existing data storage solutions have been designed for centralized as well as distributed settings; yet they do not address the security and cooperation issues raised by self-organization. P2P systems also introduce new needs regarding data availability due to the dynamicity of the infrastructure, which are unaddressed so far. This paper first discusses the approaches for tackling these problems. A solution is then introduced that relies on self-organizing security mechanisms in conjunction with a data rejuvenation scheme using erasure codes

Infection of Human Neutrophils With Leishmania infantum or Leishmania major Strains Triggers Activation and Differential Cytokines Release

Leishmaniases are neglected diseases, caused by intracellular protozoan parasites of the Leishmania (L.) genus. Although the principal host cells of the parasites are macrophages, neutrophils are the first cells rapidly recruited to the site of parasites inoculation, where they play an important role in the early recognition and elimination of the parasites. The nature of early interactions between neutrophils and Leishmania could influence the outcome of infection. Herein we aimed to evaluate whether different Leishmania strains, responsible for distinct clinical manifestations, could influence ex vivo functional activity of neutrophils. Human polymorphonuclear leukocytes were isolated from 14 healthy volunteers and the ex vivo infection of these cells was done with two L. infantum and one L. major strains. Infection parameters were determined and neutrophils activation was assessed by oxidative burst, degranulation, DNA release and apoptosis; cytokine production was measured by a multiplex flow cytometry analysis. Intracellular amastigotes were rescued to determine Leishmania strains survival. The results showed that L. infantum and L. major promastigotes similarly infected the neutrophils. Oxidative burst, neutrophil elastase, myeloperoxidase activity and apoptosis were significantly increased in infected neutrophils but with no differences between strains. The L. infantum-infected neutrophils induced more DNA release than those infected by L. major. Furthermore, Leishmania strains induced high amounts of IL-8 and stimulated the production of IL-1β, TNF-α, and TGF-β by human neutrophils. We observed that only one strain promoted IL-6 release by these neutrophils. The production of TNF-α was also differently induced by the parasites strains. All these results demonstrate that L. infantum and L. major strains were able to induce globally a similar ex vivo activation and apoptosis of neutrophils; however, they differentially triggered cytokines release from these cells. In addition, rescue of intracellular parasites indicated different survival rates further emphasizing on the influence of parasite strains within a species on the fate of infection

Analysis of the impact of the SARS-CoV-2 infection on the pediatric population hospitalized during the pandemic in the Greater Paris University Hospitals

BackgroundThe clinical characteristics, disease progression and outcome in children affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appear significantly milder compared to older individuals. Nevertheless, the trends in hospitalization and clinical characteristics in the pediatric population seem to be different over time across the different epidemic waves.ObjectiveOur aim was to understand the impact of the different COVID-19 variants in the pediatric population hospitalized in the Pediatric Departments of the Public Hospital in the Greater Paris area by the analysis performed with the Assistance Publique-Hopitaux de Paris (AP-HP) Health Data Warehouse.MethodsThis is a retrospective cohort study including 9,163 patients under 18 years of age, hospitalized from 1 March 2020 to 22 March 2022, in the Paris area, with confirmed infection by SARS-CoV-2. Three mutually exclusive groups with decreasing severity (Pediatric Inflammatory Multisystem Syndrome (PIMS), symptomatic infection, mild or asymptomatic infection) were defined and described regarding demography, medical history, complication of the SARS-CoV-2 infection, and treatment during admission. Temporal evolution was described by defining three successive waves (March–September 2020, October 2020–October 2021, and November 2021–March 2022) corresponding to the emergence of the successive variants.ResultsIn the study period, 9,163 pediatric patients with SARS-CoV-2 infection were hospitalized in 21 AP-HP hospitals. The number of patients with SARS-CoV-2 infection increased over time for each wave of the pandemic (the mean number of patients per month during the first wave was 332, 322 during the 2nd, and 595 during the third wave). In the medical history, the most associated concomitant disease was chronic respiratory disease. Patients hospitalized during the third wave presented a higher incidence of pulmonary involvement (10.2% compared to 7% and 6.5% during the first and second waves, respectively). The highest incidence of PIMS was observed during the first and second waves (4.2% in the first and second waves compared to 2.3% in the 3rd wave).DiscussionThis analysis highlighted the high incidence of hospitalized children in the Greater Paris Area during the third wave of SARS-CoV-2 pandemic corresponding to the Omicron Covid-19 variant, which is probably an expression of a concomitant SARS-CoV-2, while a decreased incidence of PIMS complication was observed during the same period

Ketogenic diet for super-refractory status epilepticus (SRSE) with NORSE and FIRES: Single tertiary center experience and literature data

Background and purposeKetogenic diet (KD) is an emerging treatment option for super-refractory status epilepticus (SRSE). We evaluated the effectiveness of KD in patients presenting SRSE including NORSE (and its subcategory FIRES).MethodsA retrospective review of the medical records was performed at the Necker Enfants Malades Hospital. All children with SRSE in whom KD was started during the last 10 years were included. A systematic search was carried out for all study designs, including at least one patient of any age with SRSE in whom KD was started. The primary outcome was the responder rate and Kaplan–Meier survival curves were generated for the time-to-KD response. As secondary outcomes, Cox proportional hazard models were created to assess the impact of NORSE-related factors on KD efficacy.ResultsSixteen children received KD for treatment of SRSE, and three had NORSE presentation (one infectious etiology, two FIRES). In medical literature, 1,613 records were initially identified, and 75 were selected for review. We selected 276 patients receiving KD during SRSE. The most common etiology of SRSE was acute symptomatic (21.3%), among these patients, 67.7% presented with NORSE of immune and infectious etiologies. Other etiologies were remote symptomatic (6.8%), progressive symptomatic (6.1%), and SE in defined electroclinical syndromes (14.8%), including two patients with genetic etiology and NORSE presentation. The etiology was unknown in 50.7% of the patients presenting with cryptogenic NORSE, of which 102 presented with FIRES. Overall, most patients with NORSE benefit from KD (p < 0.004), but they needed a longer time to achieve RSE resolution after starting KD compared with other non-NORSE SRSE (p = 0.001). The response to KD in the NORSE group with identified etiology compared to the cryptogenic NORSE was significantly higher (p = 0.01), and the time to achieve SE resolution after starting KD was shorter (p = 0.04).ConclusionsThe search for underlying etiology should help to a better-targeted therapy. KD can have good efficacy in NORSE; however, the time to achieve SE resolution seems to be longer in cryptogenic cases. These findings highlight the therapeutic role of KD in NORSE, even though this favorable response needs to be better confirmed in prospective controlled studies

Assessment of self-perceived knowledge of key clinical pharmacology concepts and educational needs among European Paediatric Intensive Care Units: an ESPNIC survey

Background: Knowledge of clinical pharmacology concepts is essential to improve patients’ outcomes. Scarce data is available on the utilisation of these concepts in the paediatric intensive care unit (PICU). We aimed to investigate the self-perceived knowledge of clinical pharmacology concepts, educational needs and identify priorities for pharmacological research across European PICUs. Methods: From July to November 2022 an online survey was distributed to evaluate i) the self-reported knowledge, and ii) application of key pharmacology concepts in clinical practice (using a likert scale from 1 = never apply to 10 = always apply); iii) need for additional education on them; and iv) key areas for future pharmacological research. The survey was distributed to European Society of Paediatric and Neonatal Intensive Care (ESPNIC) members and other European national PICUs societies members. Results: Two-hundred-thirty-seven responses from 149 PICUs were collected. 54% of PICUs reported to have a clinical pharmacologist available for consultation during drug prescription and 65% of them regularly contact them during the prescribing process. Among clinical pharmacology concepts the parameter with the highest self-reported knowledge was half-life (99%) and the lowest were pharmacodynamics and volume-of-distribution (92%). The reported median application of these concepts in clinical practice ranged between 5/10 and 7/10. Most of the respondents reported the need for additional education on specific pharmacology concepts. Reported priorities for drug research mostly involved analgesics/sedatives (87%), antimicrobials (86%), and cardiovascular medications (55%). Conclusions: Self-reported knowledge on clinical pharmacology concepts seems good, but self-perceived clinical application may improve and most of the respondents report a need for additional education. These findings call for concerted multidisciplinary efforts to streamline education and guidelines to fill this gap

recommendations by the Conect4Children expert advice group

Funding Information: Competing interests: A.V.R. has received Speaker fees/Consultant for Abbvie, Novartis, UCB, SOBI, Eli Lilly and Roche. N.M. reports grants outside the submitted work in the last five years from the Medical Research Council, National Institute of Health Research, March of Dimes, British Heart Foundation, HCA international, Health Data Research UK, Shire Pharmaceuticals, Chiesi Pharmaceuticals, Prolacta Life Sciences, and Westminster Children’s Research Fund; N.M. is a member of the Nestle Scientific Advisory Board and accepts no personal remuneration for this role. N.M. reports travel and accommodation reimbursements from Chiesi, Nestle and Shire. N.M. is a member of C4C, International Neonatal Collaboration (INC), UK National Research Ethics Advisory Service and MHRA advisory groups and/or working parties. S.W. has received compensation as a member of the scientific advisory board of AM Pharma, Novartis and Khondrion and receives research funding from IMI2 for the Conect4children project. B.A. has worked for GlaxoSmithKline between October 2006 and September 2009 and holds company shares. Between October 2009 and May 2015, she has worked for Novartis. M.S. has recieved research grant and honoraria for meetings and Advisory Boards from Alexion, Sanofi/Genzyme, Takeda, CHIESI, Ultragenix, Orchard, Orphazyme. P.I. is a permanent employee of Bayer AG, Germany. M.V. has received compensation for Advisory boards or Steering committes from Roche, Novartis, Achillion, Apellis, Retrophin/Travere, Alexion pharmaceuticals. C.M. has been a consultant to or has received honoraria from Janssen, Angelini, Servier, Nuvelution, Otsuka, Lundbeck, Pfizer, Neuraxpharm and Esteve outside the submitted work. She declares conflicts of interest unrelated to the present work. M.C. had advisory roles for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Lilly, and Roche in the last 2 years (outside the topic of the submitted work, for oncology drugs). M.J. has received research grants from Shire and has been engaged as a speaker or consultant by Shire, Ginsana, PCM Scientific Evolan, and New Nordic, all unrelated to the present work. P.S. has received speaker fees and participated at advisory boards for Biomarin, Zogenyx, GW Pharmaceuticals, and has received research funding by ENECTA BV, GW Pharmaceuticals, Kolfarma srl., Eisai. E.R. has received speaker fees and participated at advisory boards for Eisai and has received research funding by GW Pharmaceuticals, Pfizer, Italian Ministry of Health (MoH) and the Italian Medicine Agency (AIFA). This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (legge 232 del 2016). M.A.R. is a member of the c4c Ethics Expert Group and received compensation for ethical consulting activities from Bayer AG Wallace Crandall is employee of Eli Lilly and Co. P.C. is an employee of UCB, and owns stock in the company. She was previously an employee of GSK and owns stock in the company. N.R. has received honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB. The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions from the following industries in the last 3 years: Bristol Myers and Squibb, Eli-Lilly, F Hoffmann-La Roche, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties. M.L. receives/has received consultation fees from CSL Behring, Novartis, Roche and Octopharma, travel grants from Merck Serono, and been awarded educational grants to organise meetings by Novartis, Biogen Idec, Merck Serono and Bayer. All other authors have no disclosures. Funding Information: Conect4children has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777389. The Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The views expressed in this article are the personal views of the author(s) and should not be interpreted as made on behalf of, or reflecting the position of, the regulatory agency/agencies or organisations with which the author(s) is/are employed/affiliated . Publisher Copyright: © 2021, The Author(s).Background: The COVID-19 pandemic has had a devastating impact on multiple aspects of healthcare, but has also triggered new ways of working, stimulated novel approaches in clinical research and reinforced the value of previous innovations. Conect4children (c4c, www.conect4children.org) is a large collaborative European network to facilitate the development of new medicines for paediatric populations, and is made up of 35 academic and 10 industry partners from 20 European countries, more than 50 third parties, and around 500 affiliated partners. Methods: We summarise aspects of clinical research in paediatrics stimulated and reinforced by COVID-19 that the Conect4children group recommends regulators, sponsors, and investigators retain for the future, to enhance the efficiency, reduce the cost and burden of medicines and non-interventional studies, and deliver research-equity. Findings: We summarise aspects of clinical research in paediatrics stimulated and reinforced by COVID-19 that the Conect4children group recommends regulators, sponsors, and investigators retain for the future, to enhance the efficiency, reduce the cost and burden of medicines and non-interventional studies, and deliver research-equityWe provide examples of research innovation, and follow this with recommendations to improve the efficiency of future trials, drawing on industry perspectives, regulatory considerations, infrastructure requirements and parent–patient–public involvement. We end with a comment on progress made towards greater international harmonisation of paediatric research and how lessons learned from COVID-19 studies might assist in further improvements in this important area.publishersversionepub_ahead_of_prin