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Supplementary Data from Pilot Study of Vaccination with Recombinant CEA-MUC-1-TRICOM Poxviral-Based Vaccines in Patients with Metastatic Carcinoma

Purpose: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points.Experimental Design: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function–associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination.Results: The vaccine was well tolerated. Apart from injection-site reaction, no grade ≥2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis.Conclusions: This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.

Emergency management of deliberate self-poisoning (DSP) by drug overdose is common in emergency medicine. There is a paucity of data about the prehospital care of these patients. The principal aim was to describe the intensity of care received by patients with DSP who were managed by prehospital emergency medical service (EMS) physicians. A 48-h cross-sectional study was conducted in 319 EMS and emergency units in France. Patient and poisoning characteristics and treatments administered were recorded. Complications of poisoning, hospitalization, intensive care unit admission and death were recorded until day 30. The primary endpoint was the probability of receiving prehospital intensive care, including fluid resuscitation, vasopressor therapy, invasive ventilation, or antidotal treatments, depending whether prehospital treatment was carried out by an EMS physician or not. Data from 703 patients (median age was 43 [30-52] years, 288 (40%) men) were analyzed. One hundred and fifteen (16%) patients were attended by an EMS physician. Patients attended by EMS physicians were more likely to receive intensive treatment in the prehospital setting [odds ratio (OR) 7.4, 95% confidence interval 4.3-12.9]. These patients had more severe poisoning as suggested mainly by a lower Glasgow Coma Score (13 [8-15] vs. 15 [15-15]; p \textless 0.001) and a higher rate of admission to an intensive care unit [29 (25%) vs. 15 (2%), p \textless 0.001]. Patients with DSP attended by prehospital EMS physicians frequently received intensive care. The level of care seemed appropriate for the severity of the poisoning.

Colloque avec actes et comité de lecture. Internationale.; International audience; The risk of wake vortex encounter is a major issue in aviation. This is notably true in the vicinity of airports during take-o? and landing. In order to reduce wake vortex encounters, conservative separation distances are applied. However, these distances impede on the increase of the frequency of arrivals and departures at airports by the steadily increasing tra?c. In the present work, an analysis of the control of the two-dimensional vortex dynamics close and at the ground as a mean to reduce the separation distance is carried out. The behavior of vortices in ground e?ect has been a much investigated subject, motivated by this aviation issue but also by wall bounded turbulence (Stephan et al. 2013). It has been demonstrated that vortices (Harvey et al. 1971) rebound at the ground instead of going sideways like in the inviscid situation (Lamb 1932). Vortex rebound causes vortices to stay longer above runways and increase the risk of encounters. Two control strategies are described in order to alleviate the aforementioned issue. The ?rst one is based on an optimal perturbation approach aiming at mitigating vortices by increasing perturbations growth. An analysis of the e?ect of the perturbation symmetry and horizon time, along with a physical mechanism of the transient growth processes is achieved. The second approach is based on the optimal control of the vortex position through the implementation of active blowing/suction at the ground. The maximization of the lateral position of the vortices is achieved with the idea of suppressing vortex rebound, and promoting an inviscid like kinematics of the vortices (the vortices move sideways out of the runway). The method achieves a 50% increase in the lateral position of the vortices. A physical analysis of the change induced by the control on the ?ow is detailed.

The paper reviews research conducted at ONERA over the last thirty years on the transonic buffet. We first present the transonic buffet phenomenon and we explain its importance for aeronautical applications. Then, a distinction is made between the 2D buffet produced by an airfoil and the 3D buffet that characterizes swept wings of finite span. The 2D buffet amounts to a pure oscillation of the shock phase-locked with the detachment and reattachment of the boundary layer downstream, whereas the 3D buffet takes the form of a pocket of broadband perturbations located in a limited portion of the wing. We recall that these mechanisms were first studied in the 1980s through a series of tests conducted in the transonic wind tunnel ONERA T2 at Toulouse and in the large transonic wind tunnel ONERA S2Ma at Modane. Since this pioneering work, progress in the measurement techniques has led to the constitution of a comprehensive database of the 2D buffet that we describe. This database, obtained in the wind tunnel ONERA S3Ch at Meudon, has been extensively used to validate various CFD tools, with the latter being used in turn to investigate the buffet physics. We illustrate this collaboration between simulation and physics by recalling that a linear stability analysis of accurate Reynolds-Averaged-Navier-Stokes (RANS) solutions made it possible to prove that the buffet on a 2D airfoil stems from a global instability mechanism. We also review more recent tests done in the case of a laminar airfoil, which reveal very distinct behaviors of the buffet flow. This illustrates how sensitive the buffet is to the nature of the boundary layer. The last section of the paper gives a short overview of advanced simulations for these different test cases. In the conclusion, we list research perspectives, which include some more general topics such as data assimilation., AerospaceLab Journal, Issue 12, December 2016; ISSN: 2107-6596

International audience; The paper reviews research conducted at ONERA over the last thirty years on the transonic buffet. We first present the transonic buffet phenomenon and we explain its importance for aeronautical applications. Then, a distinction is made between the 2D buffet produced by an airfoil and the 3D buffet that characterizes swept wings of finite span. The 2D buffet amounts to a pure oscillation of the shock phase-locked with the detachment and reattachment of the boundary layer downstream, whereas the 3D buffet takes the form of a pocket of broadband perturbations located in a limitedportion of the wing. We recall that these mechanisms were first studied in the 1980s through a series of tests conducted in the transonic wind tunnel ONERA T2 at Toulouse and in the large transonic wind tunnel ONERA S2Ma at Modane. Since this pioneering work, progress in the measurement techniques has led to the constitution of a comprehensive database of the 2D buffet that we describe. This database, obtained in the wind tunnel ONERA S3Ch at Meudon, has been extensively used to validate various CFD tools, with the latter being used in turn to investigate the buffet physics. We illustrate this collaboration between simulation and physics by recalling that a linear stability analysis of accurate Reynolds-Averaged-Navier-Stokes (RANS) solutions made it possible to prove that the buffet on a 2D airfoil stems from a global instability mechanism.We also review more recent tests done in the case of a laminar airfoil, which reveal very distinct behaviors of the buffet flow. This illustrates how sensitive the buffet is to the nature of the boundary layer. The last section of the paper gives a short overview of advanced simulations for these different test cases. In the conclusion, we list research perspectives, which include some more general topics such as data assimilation.; L'article passe en revue les recherches menées à l'ONERA au cours des trente dernières années sur le buffet transsonique. Nous présentons d'abord le phénomène du buffet transsonique et nous expliquons son importance pour les applications aéronautiques. On distingue ensuite le buffet 2D produit par une aile bidimensionnelle et le buffet 3D qui caractérise les ailes en flèches d’envergure finie. Le buffet 2D se présente sous la forme d’une oscillation d’ensemble de tout l’écoulement couplant un déplacement de l’onde de choc et le décollement de la couche limite en aval de ce choc. Le buffet 3D prend quant à lui la forme d'une poche de perturbations localisées dans une portion limitée de l'aile. Nous rappelons que ces mécanismes ont d'abord été étudiés à l’ONERA dans les années 80 à travers une série de tests réalisés dans la soufflerie transsonique T2 à Toulouse et dans la grande soufflerie transsonique S2 de Modane. Ces travaux pionniers ont ensuite été approfondis dans la soufflerie S3Ch de Meudon de manière à élaborer une base de données complète du buffet 2D sur une aile 2D en régime turbulent, que nous décrivons. Cette base de données a été utilisée de façon extensive, à l’ONERA et dans d’autres institutions pour valider différents outils de simulation, ces derniers étant alors utilisés à leur tour pour étudier la physique du buffet. Nous illustrons cette collaboration entre la simulation et la physique en rappelant qu'une analyse de stabilité linéaire de solutions précises des équations de Navier-Stokes moyennées au sens de Reynolds (RANS) a permis de prouver que le buffet 2D provient d'un mécanisme d'instabilité globale. Nous passons également en revue des essais plus récents réalisés dans la soufflerie S3Ch sur le cas d'une aile 2D laminaire qui révèlent des comportements très distincts par rapport au cas turbulent. Cela illustre la sensibilité du buffet à la nature de la couche limite. Le dernier paragraphe du document donne un bref aperçu des simulations avancées de ces différents cas tests. Dans la conclusion, nous énumérons les perspectives de recherche sur le sujet, qui incluent aussi des thématiques méthodologiques plus générales telles que l'assimilation de données.

This paper deals with cavity flow physics and its passive control by means of a spanwise cylinder. Two configurations are considered. First, a laminar study of a flow over an unconfined square cavity at a low Reynolds number (7500) is presented. Global stability results are shown, allowing the identification of the driving mechanisms of the cavity flow: the aeroacoustic feedback mechanism and the acoustic resonance mechanism. When both mechanisms interact, the growth rate of the global modes is seen to display a local maximum. At low Mach numbers, we suggest that it is still the feedback aeroacoustic mechanism that selects the frequency mode, the acoustic resonance mechanism only enhancing the response. Second, we study the dynamics of a turbulent deep cavity flow in a transonic regime. Global modes and sensitivity results are shown and compared to experimental data, with and without control cylinder. Concerning the baseline (without control), RANS and URANS simulations, based on the k-ω model of Wilcox, display very good agreement with experiments. Also, the sensitivity map obtained numerically is extremely close to the experimental control map obtained by moving a small control cylinder in the usptream boundary layer and the shear-layer. Different interpretation elements are discussed., Journal Aerospace Lab, Issue 6, June 2013; ISSN: 2107-6596