A Canadian Critical Care Trials Group project in collaboration with the international forum for acute care trialists - Collaborative H1N1 Adjuvant Treatment pilot trial (CHAT): study protocol and design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes.</p> <p>Methods/Design</p> <p>A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates.</p> <p>Discussion</p> <p>Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic.</p> <p>Trial Registration Number</p> <p><a href="http://www.controlled-trials.com/ISRCTN45190901">ISRCTN45190901</a></p

Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets

Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza

Processus bidimensionnels et modele autoregressif vectoriel ; application a la modelisation des textures

Cet article propose l'utilisation d'un modèle vectoriel pour l'identification des processus à 2 indices ; les principaux résultats concernant l'estimation linéaire vectorielle sont présentés : nous analysons, en particulier, les relations entre la factorisation des matrices de corrélation et différentes normalisations de l'algorithme de Robinson. Nous montrons que certains polynomes à 2 variables orthogonaux sur le cercle unité sont obtenus en utilisant un algorithme récursif d'estimation des processus vectoriels ; ces polynomes sont associés au filtre bidimensionnel récursif le plus général (filtre demi-plan asymétrique) ; cette méthode est ensuite utilisée pour la modélisation des Textures

Quelques proprietes importantes du modele autoregressif vectoriel

Dans cet article nous étudions les méthodes d'estimation des moindres carrés et du maximum de vraisemblance pour le modèle autorégressif vectoriel. Plusieurs résultats nouveaux sont présentés ; nous montrons, en particulier, que comme dans le cas scalaire, les deux méthodes conduisent au même ensemble de paramètres estimés. Nous démontrons ensuite une propriété intéressante de la formulation des moindres carrés et du maximum de vraisemblance : l'estimation du modèle autorégressif vectoriel est réalisée en minimisant l'erreur de prédiction pour chacune des composantes du signal vectoriel. Plusieurs formes canoniques du modèle autorégressif vectoriel sont proposées, et nous étudions en détail, les propriétés algébriques et les propriétés de stabilité des algorithmes normalisés correspondants. Nous présentons, ensuite, plusieurs critères de reconnaissance qui se déduisent des méthodes d'estimation précédentes

Dendritic cells transduced with an adenovirus vector enconding Epstein-Barr virus latent mebrane protein 2B: a new modality for vaccination

Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignancies, particularly in immunocompromised hosts. As a strategy for stimulating immunity against EBV for the treatment of EBV-associated tumors, we have genetically engineered dendritic cells (DC) to express EBV antigens, such as latent membrane protein 2B (LMP2B), using recombinant adenovirus vectors. CD8(+) T lymphocytes from HLA-A2.1(+), EBV-seropositive healthy donors were cultured with autologous DC infected with recombinant adenovirus vector AdEGFP, encoding an enhanced green fluorescent protein (EGFP), or AdLMP2B at a multiplicity of infection of 250. After 48 h, >95% of the DC were positive far EGFP expression as assessed by fluorescence-activated cell sorting analysis, indicating efficient gene transfer. AdLMP2-transduced DC were used to stimulate CD8(+) T cells. Responder CD8(+) T cells were tested for gamma interferon (IFN-gamma) release by enzyme-linked spot (ELISPOT) assay and cytotoxic activity. Prior to in vitro stimulation, the frequencies of T-cells directed against two HLA-A2-presented LMP2 peptides (LMP2 329-337 and LMP2 426-434) were very low as assessed by IFN-gamma spot formation (T-cell frequency, <0.003%)). IFN-gamma ELISPOT assays performed at day 14 showed a significant (2-log) increase of the day 0 frequency of T cells reactive against the LMP2 329-337 peptide, from 0.003 to 0.3 (P < 0.001). Moreover, specific cytolytic activity was observed against the autologous EBV B-lymphoblastoid cell lines after 21 days of stimulation of T-cell responders with AdLMP2-transduced DC (P < 0.01), In summary, autologous mature DC genetically modified with an adenovirus encoding EBV antigens stimulate the generation of EBV-specific CD8(+) effector T cells in vitro, supporting the potential application of EBV-based adenovirus vector vaccination for the immunotherapy of the EBV-associated malignancies

Yet another survey on image segmentation: Region and boundary information integration

Abstract. Image segmentation has been, and still is, a relevant research area in Computer Vision, and hundreds of segmentation algorithms have been proposed in the last 30 years. However, it is well known that elemental segmentation techniques based on boundary or region information often fail to produce accurate segmentation results. Hence, in the last few years, there has been a tendency towards algorithms which take advantage of the complementary nature of such information. This paper reviews different segmentation proposals which integrate edge and region information and highlights 7 different strategies and methods to fuse suchinformation. In contrast withother surveys which only describe and compare qualitatively different approaches, this survey deals with a real quantitative comparison. In this sense, key methods have been programmed and their accuracy analyzed and compared using synthetic and real images. A discussion justified with experimental results is given and the code is available on Internet