85 research outputs found
Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications
Superparamagnetic iron oxide nanoparticles
can providemultiple benefits for biomedical applications
in aqueous environments such asmagnetic separation or
magnetic resonance imaging. To increase the colloidal
stability and allow subsequent reactions, the introduction
of hydrophilic functional groups onto the particlesâ
surface is essential. During this process, the original
coating is exchanged by preferably covalently bonded
ligands such as trialkoxysilanes. The duration of the
silane exchange reaction, which commonly takes more
than 24 h, is an important drawback for this approach. In
this paper, we present a novel method, which introduces
ultrasonication as an energy source to dramatically
accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove
the generic character, different functional groups were
introduced on the surface including polyethylene glycol
chains, carboxylic acid, amine, and thiol groups. Their
colloidal stability in various aqueous buffer solutions as
well as human plasma and serum was investigated to
allow implementation in biomedical and sensing
applications.status: publishe
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ÎČ, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1ÎČ innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
BACKGROUND:
The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.
METHODS:
In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
RESULTS:
At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91).
CONCLUSIONS:
Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)
Quantitative elastography of breast tumors and response to treatment
Introduction : LâĂ©lastographie shear wave (ESW) est une technique rĂ©cente dâĂ©chographie qui Ă©value quantitativement la duretĂ© des tissus et permet dâamĂ©liorer la caractĂ©risation des lĂ©sions mammaires. Comme toute nouvelle technique dâimagerie, lâESW nĂ©cessite une validation prĂ©clinique pour dĂ©finir les conditions dâutilisations et Ă©tablir les limites des champs dâapplications dans lesquelles la technique pourra ĂȘtre considĂ©rĂ©e comme valide. MatĂ©riels et mĂ©thodes : Dans une premiĂšre partie effectuĂ©e au laboratoire de recherche en Imagerie nous avons Ă©tudiĂ© les Ă©lĂ©ments histologiques sous tendant lâimage dâESW sur un modĂšle de cancer du sein implantĂ© chez la souris, au cours de sa croissance puis sous traitement. Dans une deuxiĂšme partie, nous avons Ă©tudiĂ© chez des patientes le rĂŽle de la compression manuelle en ESW pour la caractĂ©risation des lĂ©sions mammaires. Dans une derniĂšre partie, effectuĂ©e en collaboration avec une Ă©quipe de lâInstitut Langevin Ondes et Images, nous avons Ă©tudiĂ© la faisabilitĂ© dâun nouveau paramĂštre, le module de cisaillement non linĂ©aire pour lâanalyse des lĂ©sions mammaires. RĂ©sultats : Au laboratoire, nous avons Ă©tabli des corrĂ©lations entre la duretĂ© mesurĂ©e en Ă©lastographie et les caractĂ©ristiques histologiques des tumeurs, y compris sous traitement. Nous avons montrĂ© que la fibrose Ă©tait associĂ©e Ă une duretĂ© Ă©levĂ©e et la nĂ©crose Ă une duretĂ© moindre. Notre Ă©tude clinique a montrĂ© quâune compression manuelle minimale Ă©tait nĂ©cessaire pour obtenir de bonnes performances de lâESW et quâune pression trop Ă©levĂ©e devait ĂȘtre Ă©vitĂ©e. Enfin nous avons montrĂ© la faisabilitĂ© en imagerie mammaire dâun nouveau paramĂštre quantitatif obtenu en Ă©lastographie shear wave : le module de cisaillement non linĂ©aire. Conclusion : A partir de travail de thĂšse, une meilleure comprĂ©hension de la part des Ă©lĂ©ments biologiques et techniques en ESW du sein est possible et des recommandations pour lâutilisation clinique peuvent ĂȘtre formulĂ©es. Nos observations cliniques ont entrainĂ© la mise au point dâun nouveau paramĂštre diagnostique quantitatif : le module de cisaillement non linĂ©aire.Introduction: Shear Wave Elastography (SWE) is a recent ultrasound technique assessing quantitatively tissue stiffness and improving breast lesions characterization. As every new imaging technique, SWE requires a pre clinical validation in order to define in which conditions it should be used and precise the applications for which the technique is validated. Materials and methods: First, in a research lab we have investigated the pathological features underlying SWE image in a breast cancer model implanted in mice, during tumor growth and under therapy. Secondly, we have studied in patients the role of manual compression in SWE for the characterization of breast lesions. Finally, in collaboration with on team from Institut Langevin Ondes et Images, we have studied the feasibility of a new parameter, the non-linear modulus, for breast lesion assessment. Results: in the research lab, we have shown correlations between stiffness as measured with SWE and pathological features of tumors, even on treatment. We have shown that fibrosis was associated with high stiffness values and necrosis with lowers. Our clinical study, showed that a minimal manual compression was required for optimal performance of SWE and that strong compression should be avoided. Finally, we demonstrated feasibility of a new parameter, derived from SWE, the non-linear modulus. Conclusion: Our work provides a better understanding of biological and technical elements of SWE. On the basis of our results, new recommendations may be made for the use of SWE in clinical practice. From our clinical findings, we developed a new quantitative parameter, which may be useful for the diagnosis of breast lesions, the non-linear modulus
Elastographie quantitative des tumeurs du sein et de la réponse au traitement
Introduction: Shear Wave Elastography (SWE) is a recent ultrasound technique assessing quantitatively tissue stiffness and improving breast lesions characterization. As every new imaging technique, SWE requires a pre clinical validation in order to define in which conditions it should be used and precise the applications for which the technique is validated. Materials and methods: First, in a research lab we have investigated the pathological features underlying SWE image in a breast cancer model implanted in mice, during tumor growth and under therapy. Secondly, we have studied in patients the role of manual compression in SWE for the characterization of breast lesions. Finally, in collaboration with on team from Institut Langevin Ondes et Images, we have studied the feasibility of a new parameter, the non-linear modulus, for breast lesion assessment. Results: in the research lab, we have shown correlations between stiffness as measured with SWE and pathological features of tumors, even on treatment. We have shown that fibrosis was associated with high stiffness values and necrosis with lowers. Our clinical study, showed that a minimal manual compression was required for optimal performance of SWE and that strong compression should be avoided. Finally, we demonstrated feasibility of a new parameter, derived from SWE, the non-linear modulus. Conclusion: Our work provides a better understanding of biological and technical elements of SWE. On the basis of our results, new recommendations may be made for the use of SWE in clinical practice. From our clinical findings, we developed a new quantitative parameter, which may be useful for the diagnosis of breast lesions, the non-linear modulus.Introduction : LâĂ©lastographie shear wave (ESW) est une technique rĂ©cente dâĂ©chographie qui Ă©value quantitativement la duretĂ© des tissus et permet dâamĂ©liorer la caractĂ©risation des lĂ©sions mammaires. Comme toute nouvelle technique dâimagerie, lâESW nĂ©cessite une validation prĂ©clinique pour dĂ©finir les conditions dâutilisations et Ă©tablir les limites des champs dâapplications dans lesquelles la technique pourra ĂȘtre considĂ©rĂ©e comme valide. MatĂ©riels et mĂ©thodes : Dans une premiĂšre partie effectuĂ©e au laboratoire de recherche en Imagerie nous avons Ă©tudiĂ© les Ă©lĂ©ments histologiques sous tendant lâimage dâESW sur un modĂšle de cancer du sein implantĂ© chez la souris, au cours de sa croissance puis sous traitement. Dans une deuxiĂšme partie, nous avons Ă©tudiĂ© chez des patientes le rĂŽle de la compression manuelle en ESW pour la caractĂ©risation des lĂ©sions mammaires. Dans une derniĂšre partie, effectuĂ©e en collaboration avec une Ă©quipe de lâInstitut Langevin Ondes et Images, nous avons Ă©tudiĂ© la faisabilitĂ© dâun nouveau paramĂštre, le module de cisaillement non linĂ©aire pour lâanalyse des lĂ©sions mammaires. RĂ©sultats : Au laboratoire, nous avons Ă©tabli des corrĂ©lations entre la duretĂ© mesurĂ©e en Ă©lastographie et les caractĂ©ristiques histologiques des tumeurs, y compris sous traitement. Nous avons montrĂ© que la fibrose Ă©tait associĂ©e Ă une duretĂ© Ă©levĂ©e et la nĂ©crose Ă une duretĂ© moindre. Notre Ă©tude clinique a montrĂ© quâune compression manuelle minimale Ă©tait nĂ©cessaire pour obtenir de bonnes performances de lâESW et quâune pression trop Ă©levĂ©e devait ĂȘtre Ă©vitĂ©e. Enfin nous avons montrĂ© la faisabilitĂ© en imagerie mammaire dâun nouveau paramĂštre quantitatif obtenu en Ă©lastographie shear wave : le module de cisaillement non linĂ©aire. Conclusion : A partir de travail de thĂšse, une meilleure comprĂ©hension de la part des Ă©lĂ©ments biologiques et techniques en ESW du sein est possible et des recommandations pour lâutilisation clinique peuvent ĂȘtre formulĂ©es. Nos observations cliniques ont entrainĂ© la mise au point dâun nouveau paramĂštre diagnostique quantitatif : le module de cisaillement non linĂ©aire
Avenue dâOuchy 51. Logements Ă Lausanne (VD)
Claire se rĂ©veilla tĂŽt, accompagnĂ©e par les bruits du jardin. Son copain, lui, dormait encore Ă poings fermĂ©s. La partie de poker, la veille Ă leur Ă©tage, avait dĂ» se finir tard. ArrivĂ©e dans la salle-Ă -manger, elle put apercevoir, Ă travers la fenĂȘtre de la cuisine, les oiseaux qui lâavaient tirĂ©e de son sommeil. Un toast brĂ»lant Ă la main, elle devinait maintenant entre les maisons et les arbres la pointe azurĂ©e du lac en ce chaud samedi dâĂ©tĂ©. Tandis quâelle partait, une apparition de lumiĂšre dans lâimposte lui indiqua que lâappartement se rĂ©veillait tranquillement. «Quel parfum !» se dit-elle ironiquement en passant le seuil de sa porte. Lâodeur de tabac des joueurs dâhier nâavait pas encore quittĂ© les lieux malgrĂ© les fenĂȘtres toujours ouvertes. Tout en enfilant ses chaussures, elle pouvait entendre lâĂ©cho du grand escalier. Elle se pencha vers le deuxiĂšme Ă©tage et observa les deux enfants qui y jouaient. «Bonjour Claire». Anne, du premier, sortait Ă lâinstant et la salua dâun ton enjouĂ©. Un dĂ©jeuner sur le perron sâannonçait. Mais Claire nâavait pas le temps. Elle regrettait par moment dâavoir acceptĂ© ce travail. Elle aurait donnĂ© cher pour se poser un instant au jardin. En achevant de descendre les escaliers, elle dĂ©boula dans le hall dâentrĂ©e. «08:07 dĂ©jĂ !» Elle releva rapidement le courrier, et Ă grandes enjambĂ©s, traversa la cour, puis la route et sâengouffra en trombe dans le mĂ©tro. InspirĂ© de Charles-Ferdinand Ramuz, Les circonstances de la vie (1906)
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