Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT

Erosión y desertificación.-Aproximación a la evaluación de cambios de uso de suelo en la cuenca de la Rambla de las Moreras (SE de España)

RESUMEN Los cambios en el uso del suelo no son un fenómeno actual, pero en las últimas tres décadas se han registrado cambios importantes en todo el arco mediterráneo. Este trabajo lleva a cabo el análisis de la evolución de los cambios de usos de suelo acontecidos en la Cuenca de la Rambla de las Moreras, situada en el sector meridional de la Región de Murcia, entre 1956 y 2003. Para ello, la fotointerpretación integrada en Sistemas de Información Geográfica (Chuvieco, 2002; López, et al., 2002) se constituye como una metodología con gran capacidad de análisis espacial, estableciendo una clasificación de los usos de suelo más representativos en cada época. Otras variables como la pendiente del terreno, elevaciones, juegan un papel determinante en este estudio, presentando una relación directa con el uso de suelo y su evolución espacio-temporal

Additive manufacturing of continuous fibre reinforced thermoplastic composites using fused deposition modelling: Effect of process parameters on mechanical properties

Continuous Fibre Reinforced Thermoplastic Composites (CFRTPCs) are becoming alternative materials to replace the conventional thermosetting polymers and metals due to excellent mechanical performance, recycling and potential used in lightweight structures. Fused deposition modelling (FDM) is a promising additive manufacturing technology and an alternative of conventional processes for the fabrication of CFRTPCs due to its ability to build functional parts having complex geometries. The mechanical properties of a built part depend on several process parameters. The aim of this study is to characterize the effect of build orientation, layer thickness and fibre volume content on the mechanical performance of 3D printed continuous fibre reinforced composites components manufactured by a desktop 3D printer. Tensile and three-point bending tests are carried out to determine the mechanical response of the printed specimens. SEM images of fractured surfaces are evaluated to determine the effects of process parameters on failure modes. It is observed that the effect of layer thickness of nylon samples on the mechanical performance is marginally significant. In addition, continuous fibre reinforced samples show higher strength and stiffness values than unreinforced ones. The results show that carbon fibre reinforced composites exhibit the best mechanical performance with higher stiffness and flat samples exhibit higher values of strength and stiffness than on-edge samples. Additionally, the results show that strength and stiffness increase as fibre volume content increases in most cases but, conversely, the level of increment in mechanical performance is moderate with continued rise in fibre content, particularly in the case of Kevlar® and glass fibres, due to weak bonding between the fibre/nylon layers as well as the presence of increased levels of defects

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)