Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

Aims: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the {beta}-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results: In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the {beta}-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function

Effect of energy restriction and physical exercise intervention on phenotypic flexibility as examined by transcriptomics analyses of mRNA from adipose tissue and whole body magnetic resonance imaging.

Overweight and obesity lead to changes in adipose tissue such as inflammation and reduced insulin sensitivity. The aim of this study was to assess how altered energy balance by reduced food intake or enhanced physical activity affect these processes. We studied sedentary subjects with overweight/obesity in two intervention studies, each lasting 12 weeks affecting energy balance either by energy restriction (~20% reduced intake of energy from food) in one group, or by enhanced energy expenditure due to physical exercise (combined endurance- and strength-training) in the other group. We monitored mRNA expression by microarray and mRNA sequencing from adipose tissue biopsies. We also measured several plasma parameters as well as fat distribution with magnetic resonance imaging and spectroscopy. Comparison of microarray and mRNA sequencing showed strong correlations, which were also confirmed using RT-PCR In the energy restricted subjects (body weight reduced by 5% during a 12 weeks intervention), there were clear signs of enhanced lipolysis as monitored by mRNA in adipose tissue as well as plasma concentration of free-fatty acids. This increase was strongly related to increased expression of markers for M1-like macrophages in adipose tissue. In the exercising subjects (glucose infusion rate increased by 29% during a 12-week intervention), there was a marked reduction in the expression of markers of M2-like macrophages and T cells, suggesting that physical exercise was especially important for reducing inflammation in adipose tissue with insignificant reduction in total body weight. Our data indicate that energy restriction and physical exercise affect energy-related pathways as well as inflammatory processes in different ways, probably related to macrophages in adipose tissue

First fabrication of full 3D-detectors at SINTEF

International audienceA knowledge of the mechanical properties of bacterial biofilms is required to more fully understand the processes of biofilm formation such as initial adhesion or detachment. The main contribution of this article is to demonstrate the use of homogenization techniques to compute mechanical parameters of Pseudomonas aeruginosa PAO1 biofilms. For this purpose, homogenization techniques are used to analyze freeze substitution electron micrographs of the biofilm cross-sections. The concept of a representative volume element and the study about his representativeness allows us to determine the optimal size in order to analyze these biofilm images. Results demonstrate significant heterogeneities with respect to stiffness and these can be explained by varying cell density distribution throughout the bacterial biofilms. These stiffness variations lead to different mechanical properties along the height of the biofilm. Moreover, a numerical shear stress test shows the impact of these heterogeneities on the detachment process. Several modes of detachment are highlighted according to the local strain energy in the different parts of the biofilm. Knowing where, and how, a biofilm may detach will allow better prediction of accumulation and biomass detachment

Use of tracers to evaluate and optimize scale-squeeze-treatment design in the norne field

Summary When squeezing scale inhibitors (SIs) into oil-production wells, the inhibitor should usually be uniformly placed in the open intervals to optimize squeeze lifetime. In wells with varying reservoir quality and/or significant crossflow, however, uniform placement is difficult to obtain. Flow diverters are frequently used to improve the chemical placement. In many cases, it is of great interest to evaluate the squeeze performance and assess the actual placement and back production of inhibitor to gather well information and thereby optimize future squeeze designs. This can be particularly interesting in subsea wells in which other types of data collection, such as production logging, are not feasible because of high intervention costs and high operational risk. This study suggests the use of tracers during squeeze treatments to evaluate the placement as an alternative to running production-logging tools (PLTs). The main purpose of this paper is to demonstrate the applicability of tracers [in this particular study, the injection of a potassium chloride (KCl) slug in a producer well in the Norne field] to evaluate the layer flow-rate profile along the completion interval, which depends on the pressure and geological properties of each layer. The study consists of verifying the layer flow-rate profile predicted by a history-matched reservoir model. On the basis of this layer flow-rate profile, a tracer-injection program is designed, which includes two production stages at different rates. Finally, on the basis of the reservoir-model predictions, it is identified that each layer is at different pressures, which leads to a distinctive return profile. To evaluate the match between the observed data and the simulation data, the layer flow-rate profile from the reservoir model was used to populate a specialized near-wellbore model for scale-squeeze treatments. The match between the observed data and the simulated data was good. However, the near-wellbore model, in particular the layer flow-rate profile, was fine-tuned further. Finally, the fine-tuned near-wellbore model was used to optimize future treatments more accurately with the fine-tuned layer flow-rate profile.</jats:p

Effect of candesartan and metoprolol on myocardial tissue composition during anthracycline treatment: the PRADA trial

Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003). Conclusions: Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume

Results on the production of baryons with |S| = 1, 2, 3 and strange mesons in S-W collisions at 200 GeV/c per nucleon

We report results on the production of strange baryons/antibaryons with 1, 2, and 3 units of strangeness (Λ, Ξ and Ω) and mesons (Ks0, K+ and K-) in WA85 experiment at the CERN SPS. This experiment was designed to study the production of strange particles in central SW collisions at 200 GeV/c per nucleon, in the central rapidity region with medium to high pt. We have measured the inverse slopes of the mt distributions of such particles and the production ratios Λ/Λ, Ξ+/Ξ-, Ξ-/Λ, Ξ+/Λ, Ks0/Λ, Ks0/Λ, (Ω- + Ω+) (Ξ- + Ξ+) and K+ K-. Preliminary results on the production ratios Ξ-/Λ and Ξ+/Λ in pW collisions at 200 GeV/c are also presented. © 1995