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The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed.

Les postes de secours mobile (PSM) sont des dispositifs mobiles, mobilisables et projetables dont la vocation principale est la mise à disposition des intervenants de dotations médico-pharmaceutiques et logistiques conçues pour la prise en charge d’un afflux massif de victimes.

Cybersecurity in Industrial Control Systems (ICS) is a crucial problem, as recent history has shown. A notable characteristic of ICS, compared to Information Technology, is the necessity to take into account the physical process, and its specific dynamics and effects on the environment, when considering cybersecurity issues. Intrusion Detection Systems have been studied extensively. In our work, we address the less classic topic of response mechanisms, and their automation in a self-protection feedback loop. More precisely, we address self-protection seen as resilience, where the functionality of the system is maintained under attacks, be it in a degraded mode. We model this as a Discrete Event Systems supervisory control problem, involving a model of the plant’s possible behaviors, a model of considered attacks, and a formulation of the control objectives. We consider a case study, and perform a prototype implementation and simulation, using the Heptagon/BZR programming language and compiler/code generator, and targeting a multi-PLC experimental platform.

Mitochondrial diseases represent a significant clinical challenge. Substantial efforts have been devoted to identifying therapeutic strategies for mitochondrial disorders, but effective interventions have remained elusive. Recently, we reported attenuation of disease in a mouse model of the human mitochondrial disease Leigh syndrome through pharmacological inhibition of the mechanistic target of rapamycin (mTOR). The human mitochondrial disorder MELAS/MIDD (Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes/Maternally Inherited Diabetes and Deafness) shares many phenotypic characteristics with Leigh syndrome. MELAS/MIDD often leads to organ failure and transplantation and there are currently no effective treatments. To examine the therapeutic potential of mTOR inhibition in human mitochondrial disease, four kidney transplant recipients with MELAS/MIDD were switched from calcineurin inhibitors to mTOR inhibitors for immunosuppression. Primary fibroblast lines were generated from patient dermal biopsies and the impact of rapamycin was studied using cell-based end points. Metabolomic profiles of the four patients were obtained before and after the switch. pS6, a measure of mTOR signaling, was significantly increased in MELAS/MIDD cells compared to controls in the absence of treatment, demonstrating mTOR overactivation. Rapamycin rescued multiple deficits in cultured cells including mitochondrial morphology, mitochondrial membrane potential, and replicative capacity. Clinical measures of health and mitochondrial disease progression were improved in all four patients following the switch to an mTOR inhibitor. Metabolomic analysis was consistent with mitochondrial function improvement in all patients.

Que ce soient des accidents catastrophiques à effet limité (ACEL) ou des situations sanitaires exceptionnelles (SSE), ces événements engendrent des victimes, que ce soit en nombre ou selon des types de blessures spécifiques (brûlées, enfants, etc.). L’importance de la gestion efficace des victimes lors d’ACEL ou de SSE. À la suite de l’attentat du 13 novembre 2015, des outils comme SINUS et SI-VIC ont été renforcés pour suivre le parcours des victimes. Une instruction interministérielle propose une organisation interministérielle pour la prise en charge des victimes, la constitution d’un bilan victimaire et l’information des familles. La méthodologie implique l’harmonisation des termes, la temporalisation des bilans victimaires, et la collaboration avec les agences régionales de santé (ARS). L’organisation interministérielle, via des outils de traçabilité, vise à gérer l’événement et maintenir l’équilibre de l’offre de soins. Le processus inclut la prise en charge initiale sur le terrain avec des bracelets SINUS, la régulation par le SAMU, et l’accueil des victimes dans les établissements de santé. Au niveau de l’État, la gestion implique l’activation des cellules de crise, l’alerte des établissements de santé, la planification des besoins en soins, et la communication aux familles et au public. L’utilisation coordonnée des outils SINUS et SI-VIC par les professionnels est cruciale pour le suivi et la confirmation du bilan des victimes après l’événement. Tout ceci ne peut réussir que si l’ensemble des professionnels des secours et de la santé utilise les outils SINUS et SI-VIC, afin que l’ARS puisse suivre, vérifie, consolide, puis confirme le bilan des victimes après la fin de l’événement.

La protéinose alvéolaire pulmonaire auto-immune est une maladie rare, liée à l’accumulation de surfactant au niveau des alvéoles.

Moisture is known to affect the flowing properties of powders. However, the quantification and the understanding of the observed effects are far to be obvious. To study air moisture influence on powder flowability in a laboratory, a conditioning system and a precise flowmeter are necessary. Simple flow testers, which are commonly used R&D laboratories, are not able to quantify precisely the effect of moisture on powders. The use of advanced techniques is necessary. In this paper, we present how a precise and user-friendly flowability test associated with a dynamic conditioning system can be used to quantify the influence of moisture on the flowability properties of lactose powders. The effect of residence time T in high humidity conditions is analyzed. Afterward, we show that the relative humidity range that optimizes the flowability of lactose powders is between 30% and 50%. For lower values of the relative humidity, the apparition of electric charges inside the bulk induces cohesive forces. For higher relative humidity, the condensation of the air humidity at the contact between the grains forms capillary bridges which favors also the cohesive interactions. A model taking both triboelectric and capillary effects into account is proposed to fit the experimental data.

Inhalation of therapeutic aerosols has a long tradition and is, moreover, regarded as a safe and efficient route of drug administration to the respiratory tract. Especially, the targeting opportunities of this approach are beneficial for the treatment of numerous airway diseases. However, the rapid decay of local drug concentration and the resulting short-term duration of action of conventional medications necessitates several daily inhalations, which is clearly in conflict with a patients’ convenience and compliance. Recent progress in pharmaceutical engineering has provided promising drug delivery vehicles (e.g., liposomes, nanoparticles and thermo-responsive preparations) allowing for a sustained release of the encapsulated medication at the target site. Nevertheless, aspects such as generating tailored aerosols from these formulations (including stability during aerosolization) and the choice of biocompatible excipients remain considerable challenges, which need to be addressed in order to optimize inhalation therapy. Therefore, toxicology issues raised by these novel drug delivery vehicles with respect to physicochemical and material properties and biocompatibility are described in this review. This brief overview is intended to serve as a foundation to prompt future advancement in the field of controlled drug delivery to the lungs.

Le syndrome des antisynthétases correspond à une myopathie inflammatoire fréquemment associée à une atteinte pulmonaire, surtout parenchymateuse (pneumopathie infiltrante diffuse) et plus rarement vasculaire (hypertension pulmonaire). Devant un tableau clinique et radiologique évocateur, la présence d’anticorps anti-ARNt synthétases signe le diagnostic. Les plus fréquents de ces auto-anticorps sont les anti-Jo1, les anti-PL7 et les anti-PL12. De nombreuses manifestations cliniques extrathoraciques associées à l’atteinte pulmonaire peuvent orienter le diagnostic : myalgies ou déficit musculaire, phénomène de Raynaud, polyarthrite, fièvre et « mains de mécaniciens ». Une augmentation des créatine-phospho-kinases est quasi constante. Le recours à l’électromyogramme, à l’imagerie musculaire par résonance magnétique ou à l’histologie n’est pas systématique. Néanmoins, il existe une grande variabilité des symptômes et de leur sévérité d’un patient à l’autre ou au long de l’évolution de la maladie. L’atteinte pulmonaire est un facteur pronostic majeur et incite à traiter de manière intensive les patients, principalement par corticothérapie systémique, voire d’emblée par association corticoïdes et immunosuppresseurs. Mieux connaître cette pathologie qui est souvent de révélation pneumologique permettrait d’améliorer le diagnostic et la prise en charge thérapeutique, voire même le pronostic.

Alpha-1 antitrypsin, secreted by the liver, inhibits neutrophil elastase. Its deficiency favours the development of emphysema. Restoring a “protective” serum level in deficient patients should make it possible to inhibit the development of emphysema.

En s'appuyant sur des calculs ab-initio des énergies des états de valence et des moments de transition, on montre que l'état fondamental de la molécule GeSi, encore inobservée en phase gazeuse, est un état triplet et que son spectre électronique d'absorption (hors-Rydberg) doit être formé de trois systèmes triplet-triplet de transfert de charge situés dans le proche ultraviolet. En émission, outre ces trois systèmes, on doit pouvoir observer une transition électronique entre singulets dans l'infrarouge. Des calculs supplémentaires sur GeSi+permettent de prévoir un état 4Σ-comme état fondamental de cet ion.

Complex computing systems are increasingly designed so that they are self-adaptive, and adopt the autonomic computing approach for their administration. Real systems require the co-existence of multiple such autonomic management loops. Their uncoordinated execution can lead to problematic interferences and jeopardize performance as well as consistency. This is a typical example of the general need for methodological support for the design of wellcoordinated managers, without breaking their natural modularity. We address the problem with a method stressing modularity, and focusing on the discrete control of the interactions of managers. This paper focusses on proposals for the distributed execution of modular controllers, first in synchronized way, and then relaxing this synchronization. We apply and validate our method on a multiple-loop multi-tier system in a data-center.

Inactivation of Rac1 by MgcRacGAP at the cleavage plane is essential to ensure cytokinesis. Trio activates Rac1 in dividing cells, and its depletion rescues the cytokinesis failure induced by MgcRacGAP. This work identifies for the first time a GEF-activating Rac1 in dividing cells that counteracts MgcRacGAP function in cytokinesis.

La protéinose alvéolaire pulmonaire (PAP) est une maladie rare caractérisée par l’accumulation alvéolaire de composants du surfactant qui gêne les échanges gazeux. Les PAP sont séparées en trois groupes : les PAP auto-immunes caractérisées par la présence d’anticorps sériques anti-GM-CSF qui sont les plus fréquentes ; les PAP secondaires à une maladie sous-jacente, le plus souvent hématologique, mais aussi à l’inhalation de toxiques et à des infections ; enfin, les PAP d’origine génétique. Le diagnostic de PAP est évoqué sur le scanner thoracique avec une pneumopathie infiltrante diffuse ayant un aspect classique de crazy paving, puis confirmé par l’aspect laiteux du lavage bronchoalvéolaire, et la présence de matériel lipoprotéinacé PAS positif. La confirmation du diagnostic de PAP par biopsie pulmonaire chirurgicale est désormais rarement nécessaire. La positivité des anticorps sériques anti-GM-CSF signe le caractère auto-immun de la maladie. Le traitement de référence des PAP auto-immunes est le « grand lavage pulmonaire thérapeutique ». En cas de maladie réfractaire, d’autres traitements sont disponibles, tels que le GM-CSF en injection sous-cutanée ou en aérosol et le rituximab. L’évolution de la maladie est imprévisible. Une évolution spontanément favorable ou même une guérison spontanée peuvent survenir et la survie actuarielle à 5ans est de 95 %. Les principales complications sont infectieuses.

L’hydroxyurée est un antimétabolite utilisé dans le traitement des maladies myéloprolifératives. Ses effets secondaires habituels sont principalement hématologiques, gastro-intestinaux, cutanés et une fièvre. Plus rarement, des pneumopathies ont été décrites.

Most bona fide centrosome proteins including centrins, small calcium-binding proteins, participate in spindle function during mitosis and play a role in cilia assembly in non-cycling cells. Although the basic cellular functions of centrins have been studied in lower eukaryotes and vertebrate cells in culture, phenotypes associated with centrin depletion in vertebrates in vivo has not been directly addressed. To test this, we depleted centrin2 in zebrafish and found that it leads to ciliopathy phenotypes including enlarged pronephric tubules and pronephric cysts. Consistent with the ciliopathy phenotypes, cilia defects were observed in differentiated epithelial cells of ciliated organs such as the olfactory bulb and pronephric duct. The organ phenotypes were also accompanied by cell cycle deregulation namely mitotic delay resulting from mitotic defects. Overall, this work demonstrates that centrin2 depletion causes cilia-related disorders in zebrafish. Moreover, given the presence of both cilia and mitotic defects in the affected organs, it suggests that cilia disorders may arise from a combination of these defects.

Condylar fracture osteosynthesis is today commonly practiced, but only a few studies deal with complications due to plates or screws loosening.

The fire‐retardant properties of a recycled poly(propylene)‐based material were investigated and compared to the non‐recycled formulation. An intrinsic intumescent system and zinc borate were used to flame‐retard these polymers. By mass loss calorimetry, the best results were obtained with 20 wt.‐% of additives. Synergisms between AP765 and ZB were observed in the non‐recycled blends but not in the recycled ones. Solid‐state NMR showed that chemical reactions during the decomposition process were leading to the formation of borophosphates, reinforcing the efficiency of the intumescent char. From a ‘physical’ point of view, it was shown that the fire retardant properties of the materials are related to the formation speed of the intumescent structure and not on the char thickness.

The drug 131I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration.

Summary:In this work, the reaction to fire of reprocessed polypropylene (PP)/Ethylene Propylene Rubber (EPR) materials containing engine oil as pollutant was investigated by mass loss calorimetry. It was compared to the behaviour of the corresponding original high impact PP material. In order to flame retard the polymers, an intumescent system was studied in combination with zinc borate (ZB) as potential synergistic agent. It is shown that 20% of additives are necessary to obtain good FR properties. The use of ZB greatly improves the reaction to fire of original PP/EPR materials due to the formation of borophosphates during the degradation process that permit to reinforce the char structure. In the case of the polluted and reprocessed formulations, ZB has no influence on the fire performance because the minerals included in the engine oil act also as a flame retardant. For the two types of materials, it is demonstrated that the expansion rate at the beginning of the intumescent process plays a crucial role in the formation of an efficient insulating layer at the surface of the substrate. On the contrary, the fire performance is not related to the thickness of the carbonaceous shield.

In this paper, a decentralised supervisory control approach for distributed adaptive systems is proposed. The adaptive systems are modelled, with their adaptation managers, as synchronous reactive systems using finite state machines with inputs/outputs and transition guards. A formal automated control synthesis technique is developed, for supervising the method of coupling adaptation managers with the system, for the purpose of ensuring important safety properties. Our approach is based on existing techniques for discrete controller synthesis, and develops controllers for decentralised systems, consisting of multiple subsystems spread across remote sites. At each site, abstracted behaviour models for each remote subsystem, is computed. In order to compensate for the lack of information caused by the distributed nature of the system, the model used at each site, consists of the abstracted models of the remote subsystems coupled with the full model of the local subsystem. Discrete controller synthesis is then applied at each site, to obtain its local controller. The site controllers then act collectively and independently, on their corresponding subsystems, to ensure that the total global system behaviour respects the given global property.

We present a novel technique for designing discrete, logical control loops, on top of continuous control tasks, ensuring logical safety properties of the tasks sequencings and mode changes. We define this new handler on top of the real-time executives built with the Orccaddesign environment for control systems, which is applied, e.g. to robotics and real-time networked control. It features structures of control tasks, each equipped with a local automaton, used for the reactive, event-based management of its activity and modes. The additional discrete handler manages the interactions between tasks, concerning, e.g., mutual exclusions, forbidden or imposed sequences. We use a new reactive programming language, with constructs for finite-state machines and data-flow nodes, and a mechanism of behavioral contracts, which involves discrete controller synthesis. The result is a discrete control loop, on top of the continuous control loops, all integrated in a coherent real-time architecture. Our approach is illustrated and validated experimentally with the case study of a robot arm.

Background: Little is known about residual abnormalities after pulmonary embolism (PE). Objectives: To assess risk factors and the clinical significance of perfusion defects in patients with PE. Patients/Methods: Consecutive patients receiving at least 3 months of anticoagulant for an acute PE were included in a prospective cohort study. Ventilation/perfusion lung scan, echocardiography, 6‐min walk test, thrombophilia and hemostatic variables were performed 6–12 months after PE. Perfusion defect was defined as a perfusion defect in at least two segments. Results: Seventy‐three out of 254 patients (29%) had perfusion defects during follow‐up (median 12 months) and were more likely to have dyspnea, had a higher systolic pulmonary arterial pressure [39 mmHg (SD) (12) vs. 31 mmHg (8); P< 0.001] and walked a shorter distance during the 6‐min walk test [374 m (122) vs. 427 m (99); P= 0.004]. Age [odds ratio (OR) 1.35; 95% confidence interval (CI), 1.11–1.63], the time interval between symptom onset and diagnosis (OR, 1.17; 95% CI, 1.04–1.31), pulmonary vascular obstruction at the onset of PE (OR, 1.34; 95% CI, 1.16–1.55) and previous venous thromboembolism (OR 2.06; 95% CI, 1.03–4.11) were independent predictors of perfusion defect after treatment of acute PE. Total tissue factor pathway inhibitor concentration was associated with perfusion defects. Conclusions: Perfusion defects are associated with an increase in pulmonary artery pressure (PAP) and functional limitation. Age, longer times between symptom onset and diagnosis, initial pulmonary vascular obstruction and previous venous thromboembolism were associated with perfusion defects.

Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2β). CHD4 is part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show that many NuRD components interacted with pericentrin by coimmunoprecipitation and that they localized to centrosomes and midbodies. Overexpression of the pericentrin-binding domain of CHD4 or another family member (CHD3) dissociated pericentrin from centrosomes. Depletion of CHD3, but not CHD4, by RNA interference dissociated pericentrin and γ-tubulin from centrosomes. Microtubule nucleation/organization, cell morphology, and nuclear centration were disrupted in CHD3-depleted cells. Spindles were disorganized, the majority showing a prometaphase-like configuration. Time-lapse imaging revealed mitotic failure before chromosome segregation and cytokinesis failure. We conclude that pericentrin forms complexes with CHD3 and CHD4, but a distinct CHD3–pericentrin complex is required for centrosomal anchoring of pericentrin/γ-tubulin and for centrosome integrity.

Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2β). CHD4 is part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show that many NuRD components interacted with pericentrin by coimmunoprecipitation and that they localized to centrosomes and midbodies. Overexpression of the pericentrin-binding domain of CHD4 or another family member (CHD3) dissociated pericentrin from centrosomes. Depletion of CHD3, but not CHD4, by RNA interference dissociated pericentrin and γ-tubulin from centrosomes. Microtubule nucleation/organization, cell morphology, and nuclear centration were disrupted in CHD3-depleted cells. Spindles were disorganized, the majority showing a prometaphase-like configuration. Time-lapse imaging revealed mitotic failure before chromosome segregation and cytokinesis failure. We conclude that pericentrin forms complexes with CHD3 and CHD4, but a distinct CHD3–pericentrin complex is required for centrosomal anchoring of pericentrin/γ-tubulin and for centrosome integrity.

Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases, regulated by endogenous tissue inhibitors (TIMPs) and inducer (EMMPRIN). The demonstration of a functional role of MMPs in pulmonary diseases raises the possibility of therapeutic intervention targeting MMP/TIMP balance to prevent pathological processes.

Objective and design: Chronic obstructive pulmonary disease (COPD) is characterized by an inflammatory process and airway remodeling involving matrix metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12 (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from COPD patients and control subjects. Methods: Immunocytochemistry and immunochemistry were performed to analyze the expression of MMP-12 in BAL cells and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in BAL fluids. Results: The number of MMP-12 expressing macrophages together with the staining intensity was higher in BAL samples from COPD patients than in controls subjects. Similar results were noted in bronchial biopsies with higher MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was also observed in BAL fluids from patient with COPD in comparison to control subjects. Conclusion: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.

ABSTRACTThe effect of continuous in-feed administration of anticoccidial agents on antimicrobial sensitivity and the level of bacterial shedding in poultry experimentally infected with Salmonella entericasubsp. entericaserotype Typhimurium definitive type 104 (DT104) were investigated. On day 0, 1,200 1-day-old Salmonella-free broiler chicks were placed into 50 pens, and the pens were randomly allocated to one of five treatments: nonsupplemented (negative control; T1), monensin at 120 mg/kg of diet (T2), salinomycin at 60 mg/kg of diet (T3), semduramicin at 20 mg/kg of diet (T4), or semduramicin at 25 mg/kg of diet (T5). Each bird was inoculated with a well-characterized strain of serotype Typhimurium DT104 on day 10. On day 49, the birds were euthanatized humanely. Bulk fecal samples were collected on days 13, 43, and 48 and were examined for organisms which had acquired resistance. The genetic basis of acquired resistance was determined from representative samples of isolates. Of 784 Salmonella-selective plates supplemented with antimicrobial agents, only 33 showed growth. These isolates came from all treatment regimens, including the nonsupplemented control. A number of phenotypic changes were observed; these included changes in motility, phage type, and agglutination properties. Supplementation of the diet with an anticoccidial drug does not appear to affect antimicrobial resistance or the level of excretion of salmonellae. Most of the changes observed do not seem to be related to the presence of a supplement in feed. Salmonellae appear to be capable of acquiring antimicrobial resistance and phenotypic changes independently of specific antimicrobial selection pressures.

An intercomparison of aerosol backscatter lidar algorithms was performed in 2001 within the framework of the European Aerosol Research Lidar Network to Establish an Aerosol Climatology (EARLINET). The objective of this research was to test the correctness of the algorithms and the influence of the lidar ratio used by the various lidar teams involved in the EARLINET for calculation of backscatter-coefficient profiles from the lidar signals. The exercise consisted of processing synthetic lidar signals of various degrees of difficulty. One of these profiles contained height-dependent lidar ratios to test the vertical influence of those profiles on the various retrieval algorithms. Furthermore, a realistic incomplete overlap of laser beam and receiver field of view was introduced to remind the teams to take great care in the nearest range to the lidar. The intercomparison was performed in three stages with increasing knowledge on the input parameters. First, only the lidar signals were distributed; this is the most realistic stage. Afterward the lidar ratio profiles and the reference values at calibration height were provided. The unknown height-dependent lidar ratio had the largest influence on the retrieval, whereas the unknown reference value was of minor importance. These results show the necessity of making additional independent measurements, which can provide us with a suitable approximation of the lidar ratio. The final stage proves in general, that the data evaluation schemes of the different groups of lidar systems work well.

An intercomparison of aerosol backscatter lidar algorithms was performed in 2001 within the framework of the European Aerosol Research Lidar Network to Establish an Aerosol Climatology (EARLINET). The objective of this research was to test the correctness of the algorithms and the influence of the lidar ratio used by the various lidar teams involved in the EARLINET for calculation of backscatter-coefficient profiles from the lidar signals. The exercise consisted of processing synthetic lidar signals of various degrees of difficulty. One of these profiles contained height-dependent lidar ratios to test the vertical influence of those profiles on the various retrieval algorithms. Furthermore, a realistic incomplete overlap of laser beam and receiver field of view was introduced to remind the teams to take great care in the nearest range to the lidar. The intercomparison was performed in three stages with increasing knowledge on the input parameters. First, only the lidar signals were distributed; this is the most realistic stage. Afterward the lidar ratio profiles and the reference values at calibration height were provided. The unknown height-dependent lidar ratio had the largest influence on the retrieval, whereas the unknown reference value was of minor importance. These results show the necessity of making additional independent measurements, which can provide us with a suitable approximation of the lidar ratio. The final stage proves in general, that the data evaluation schemes of the different groups of lidar systems work well.

In the framework of the European Aerosol Research Lidar Network to Establish an Aerosol Climatology (EARLINET), 19 aerosol lidar systems from 11 European countries were compared. Aerosol extinction or backscatter coefficient profiles were measured by at least two systems for each comparison. Aerosol extinction coefficients were derived from Raman lidar measurements in the UV (351 or 355 nm), and aerosol backscatter profiles were calculated from pure elastic backscatter measurements at 351 or 355, 532, or 1064 nm. The results were compared for height ranges with high and low aerosol content. Some systems were additionally compared with sunphotometers and starphotometers. Predefined maximum deviations were used for quality control of the results. Lidar systems with results outside those limits could not meet the quality assurance criterion. The algorithms for deriving aerosol backscatter profiles from elastic lidar measurements were tested separately, and the results are described in Part 2 of this series of papers [Appl. Opt.43, 977–989 (2004)]. In the end, all systems were quality assured, although some had to be modified to improve their performance. Typical deviations between aerosol backscatter profiles were 10% in the planetary boundary layer and 0.1 × 10^-6 m^-1 sr^-1 in the free troposphere.

Constitutive activation of aberrant fibroblast growth factor receptor 1 (FGFR1) kinase as a consequence of gene fusion such as FOP-FGFR1 associated with t(6; 8)(q27;p11-12) translocation, is the hallmark of an atypical aggressive stem cell myeloproliferative disorder (MPD) in humans. In this study, we show that expression of FOP-FGFR1 in primary bone marrow cells induced by retroviral transduction generates a MPD in mice. Constitutive FOP-FGFR1 kinase activity was both essential and sufficient to cause a chronic myeloproliferative syndrome in the murine bone marrow transplantation model. In contrast to the human disorder, lymphoproliferation and progression to acute phase were not observed. Lymphoid symptoms, however, appeared when onset of the disease was delayed as the result of mutation of FOP-FGFR1 at tyrosine 511, the phospholipase C γ (PLCγ) binding site.

Constitutive activation of aberrant fibroblast growth factor receptor 1 (FGFR1) kinase as a consequence of gene fusion such as FOP-FGFR1 associated with t(6; 8)(q27;p11-12) translocation, is the hallmark of an atypical aggressive stem cell myeloproliferative disorder (MPD) in humans. In this study, we show that expression of FOP-FGFR1 in primary bone marrow cells induced by retroviral transduction generates a MPD in mice. Constitutive FOP-FGFR1 kinase activity was both essential and sufficient to cause a chronic myeloproliferative syndrome in the murine bone marrow transplantation model. In contrast to the human disorder, lymphoproliferation and progression to acute phase were not observed. Lymphoid symptoms, however, appeared when onset of the disease was delayed as the result of mutation of FOP-FGFR1 at tyrosine 511, the phospholipase C γ (PLCγ) binding site.

Background:Giving the immunosuppressive drug tacrolimus (FK506) to liver transplant patients has helped to considerably reduce oral side effects such as gingival hyperplasia. Patients taking cyclosporin who suffer from gingival hyperplasia are often switched to tacrolimus. Methods:We present here a pediatric liver transplantation case study. The patient has been followed for 5.5 years. She developed oral lesions that resulted in the immunosuppressive therapy being changed from tacrolimus to cyclosporin. In clinical terms, the atypical pathology consisted of hyperpigmented patches on the gingival margin, the internal surfaces of the cheeks, and the intraoral surfaces of the lips. When located on the lips, the hyperpigmented patches were associated with pruriginous and edematous lesions. Results:Optical and electronic microscopic examinations of a gingival tissue sample revealed the presence of melanin incontinence and lichenoid lesions with degenerated keratinocytes and a mild infiltrate of lymphocytes. This points to a chronic graft‐versushost disease (cGvHD)‐like syndrome linked to tacrolimus. This diagnosis was given further credence by improvement in the lesions following the switch to cyclosporin. Conclusion:To our knowledge, this is the first reported case of tacrolimus‐associated chronic GvHDlike syndrome occurring in the oral mucosa.J Periodontol 2003;74:552‐556.

AbstractAmong embryonic aortic vascular malformations, persistence of a right aortic arch and aberrant left subclavian artery associated with a diverticulum of Kommerell is rare, and is estimated to occur in 0.1% of the general population. We report two cases of diverticulum of Kommerell in which tracheal compression due to the vascular ring induced respiratory symptoms such as asthmatic dyspnoea. This reminds us that at least a chest X-ray should be performed in newly diagnosed asthmatic patients, focusing on the trachea and upper mediastinum. In case of vascular abnormality, angiography and magnetic resonance are the best investigations to define the abnormal anatomy and guide surgery.Copyright © 2002 S. Karger AG, Basel

A shape classification technique for cirrus clouds that could be applied to future spaceborne lidars is presented. A ray-tracing code has been developed to simulate backscattered and depolarized lidar signals from cirrus clouds made of hexagonal-based crystals with various compositions and optical depth, taking into account multiple scattering. This code was used first to study the sensitivity of the linear depolarization rate to cloud optical and microphysical properties, then to classify particle shapes in cirrus clouds based on depolarization ratio measurements. As an example this technique has been applied to lidar measurements from 15 mid-latitude cirrus cloud cases taken in Palaiseau, France. Results show a majority of near-unity shape ratios as well as a strong correlation between shape ratios and temperature: The lowest temperatures lead to high shape ratios. The application of this technique to spaceborne measurements would allow a large-scale classification of shape ratios in cirrus clouds, leading to better knowledge of the vertical variability of shapes, their dependence on temperature, and the formation processes of clouds.

A four-element photomixer receiver has been tested in a 10-µm heterodyne Doppler lidar. It addresses a reduction of the variance of the power scattered off distributed aerosols targets at ranges as long as 8 km. An improvement in performance is expected when the four independent signals recorded on every single shot are combined. Two summation techniques of the four signals have been implemented: a coherent summation of signal amplitude and an incoherent summation of intensities. A phasing technique for the four signals is proposed. It is based on a more suitable correlation time with discernible self-consistent packets (SCP’s). The SCP technique has been successfully tested, and the results obtained with a coherent summation of the four signals, i.e., variance reduction, carrier-to-noise ratio improvement, and velocity accuracy improvement, are in agreement with theory.

Introduction: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT) conditioning that may also develop after high-dose chemotherapy. Multiorgan failure (MOF) is associated with the most severe form of VOD/SOS and, if untreated, may result in a mortality rate of >80%. Defibrotide is approved for the treatment of hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in the US and for severe hepatic VOD/SOS post-HCT in patients aged >1 month (mo) in the EU. The DEFIFrance study collected real-world data on the efficacy and safety of defibrotide from HCT centers in France. This analysis presents final, long-term data on the primary study population: patients who received defibrotide treatment for severe/very severe VOD/SOS post-HCT.

Mohty: Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Adaptive Biotechnologies: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Peffault De Latour: Amgen: Consultancy, Other, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Jazz Pharmaceuticals: Honoraria. Labopin: Jazz Pharmaceuticals: Honoraria. Detrait: Jazz Pharmaceuticals: Research Funding. Huynh: Jazz Pharmaceuticals: Honoraria. Renard: Jazz Pharmaceuticals: Research Funding. Asubonteng: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Delaval: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Dalle: Jazz Pharmaceuticals: Honoraria.