The binding of fibrinogen and fibrin to platelets is important in normal hemostasis. The extent of platelet-fibrin interaction can be measured as the viscoelastic strength of clot by rotational ...thromboelastometry (ROTEM). In this study, we investigated the effect of fibrinogen concentration and its relative contribution to overall clot strength using ROTEM.
Blood samples were collected from healthy volunteers. The effects of platelet count on clot strength, determined by maximum clot elasticity (MCE), were evaluated on ROTEM using platelet-rich plasma (PRP) adjusted with autologous plasma to generate a range of platelet counts. PRPs were adjusted to 10 x 10(3) mm(-3), 50 x 10(3) mm(-3), and 100 x 10(3) mm(-3) and spiked with fibrinogen concentrates at 550 and 780 mg/dL. The effect of fibrin polymerization on clot strength, independent of platelet attachment, was analyzed by the cytochalasin D-modified thromboelastometry (FIBTEM) method. Additional retrospective analysis of clot strength (MCE) in two groups of thrombocytopenic patients was conducted.
Clot strength (MCE) decreased at a platelet count below 100 x 10(3) mm(-3), whereas increases in MCE peaked and reached a plateau at platelet counts from 400 x 10(3) mm(-3). Increasing fibrinogen concentrations in PRP increased clot strength in a concentration-dependent manner, even at low platelet counts (10 x 10(3) mm(-3)). The positive correlation between clot strength and plasma fibrinogen level was also confirmed in the analysis of the data obtained from 904 thrombocytopenic patients.
These in vitro and clinical data indicate that the clot strength increases in a fibrinogen concentration-dependent manner independent of platelet count, when analyzed by ROTEM. The maintenance of fibrinogen concentration is critical in the presence of thrombocytopenia. EXTEM (extrinsic activation) and FIBTEM may be useful in guiding fibrinogen repletion therapy.
Inflammation in cardiac surgical patients is produced by complex humoral and cellular interactions with numerous pathways including activation, generation, or expression of thrombin, complement, ...cytokines, neutrophils, adhesion molecules, mast cells, and multiple inflammatory mediators. Because of the redundancy of the inflammatory cascades, profound amplification occurs to produce multiorgan system dysfunction that can manifest as coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive defects. Coagulation and inflammation are also closely linked through networks of both humoral and cellular components including proteases of the clotting and fibrinolytic cascades, including tissue factor. Vascular endothelial cells also mediate inflammation and the cross talk between coagulation and inflammation. Novel antiinflammatory agents inhibit these processes by several mechanisms such as preventing proteolysis of the protease-activated receptor (aprotinin), inhibiting complement-mediated injury (pexelizumab), or inhibiting contact activation (kallikrein inhibitors). Surgery alone also activates specific hemostatic responses, activation of immune mechanisms, and inflammatory response mediated by the release of various cytokines and chemokines. Novel agents are under investigation to further improve outcomes in cardiac surgical patients.
The strong coupling between antiferromagnetism and ferroelectricity at room temperature found in BiFeO3 generates high expectations for the design and development of technological devices with novel ...functionalities. However, the multi-domain nature of the material tends to nullify the properties of interest and complicates the thorough understanding of the mechanisms that are responsible for those properties. Here we report the realization of a BiFeO3 material in thin film form with single-domain behaviour in both its magnetism and ferroelectricity: the entire film shows its antiferromagnetic axis aligned along the crystallographic b axis and its ferroelectric polarization along the c axis. With this we are able to reveal that the canted ferromagnetic moment due to the Dzyaloshinskii-Moriya interaction is parallel to the a axis. Furthermore, by fabricating a Co/BiFeO3 heterostructure, we demonstrate that the ferromagnetic moment of the Co film does couple directly to the canted moment of BiFeO3.
Abstract
Electric-field control of magnetism requires deterministic control of the magnetic order and understanding of the magnetoelectric coupling in multiferroics like BiFeO
3
and EuTiO
3
. Despite ...this critical need, there are few studies on the strain evolution of magnetic order in BiFeO
3
films. Here, in (110)-oriented BiFeO
3
films, we reveal that while the polarization structure remains relatively unaffected, strain can continuously tune the orientation of the antiferromagnetic-spin axis across a wide angular space, resulting in an unexpected deviation of the classical perpendicular relationship between the antiferromagnetic axis and the polarization. Calculations suggest that this evolution arises from a competition between the Dzyaloshinskii–Moriya interaction and single-ion anisotropy wherein the former dominates at small strains and the two are comparable at large strains. Finally, strong coupling between the BiFeO
3
and the ferromagnet Co
0.9
Fe
0.1
exists such that the magnetic anisotropy of the ferromagnet can be effectively controlled by engineering the orientation of the antiferromagnetic-spin axis.
Metallic supports with sufficient surface quality to achieve highly selective thin Pd–Ag membranes require specific pre-treatments, are not readily available on the market and are generally very ...expensive. To reduce costs, rough and large media grade Hastelloy X filters have been acquired and pre-treated via polishing and chemical etching. The loss in gas permeance given by the polishing treatment proved fully recovered after chemical etching. A method to fill the large pores of the filters via aspiration of α-Al2O3 water-powder suspension has been applied and characterized via imaging of the filled pores, inferential statistics, and capillary flow porometry measurements. The most suitable filler particle size for pore size distribution reduction has been identified as 18 μm, while a 5 μm filler proved optimal for further pore morphology improvement. The wide pore size distribution of the filters has thus been reduced up to 200 nm by filling with α-Al2O3 particles of decreasing size, similarly to the ceramic supports used for thin Pd–Ag membranes deposition. A boehmite based interdiffusion barrier has been deposited, achieving further surface roughness reduction. A highly H2 selective membrane has been obtained via simultaneous Pd–Ag plating on the pre-treated filter.
Display omitted
•A method to fill the pores of Hastelloy filters via aspiration of α-Al2O3 water suspension has been developed.•The effect of α-Al2O3 particle size on the surface quality has been studied with a statistical method.•The asymmetrical filling method can reduce the average pore size of the filters from 1.1 μm up to 200 nm.•A boehmite-based layer is used to change the surface quality and as interdiffusion barrier.•A highly H2-selective Pd–Ag membrane (∼40 000) has been obtained on the asymmetrically filled support.
Although the number of global clinical trials (GCTs) conducted in multiple countries including Japan has increased recently, it is not clear how much these GCTs help in reducing the lag in drug ...development (LDD: difference between the submission dates for new drug applications (NDAs) in the United States and Japan). We examined the effects of various clinical development strategies on LDD because the development period depends on what types of clinical trials were conducted for the Japanese NDA. Although various drug development strategies are available, deciding early on an appropriate strategy is a key to minimizing the LDD in Japan. The inclusion of GCTs in the clinical development strategy is also important; simultaneously, the smaller sample size of the Japanese population should be taken into consideration. Furthermore, reinforcement of Japan's capability to lead drug development may also be important in providing innovative drugs to Japanese patients without any significant LDD.
Clinical Pharmacology & Therapeutics (2014); 95 5, 533–541. doi:10.1038/clpt.2013.223
Rice is mainly grown under rainfed conditions in West Africa. Unpredictable and variable rainfall, poor soil quality, and suboptimal crop management practices are the main determinants of low ...productivity. We assessed the effects of soil water availability and fertilizer application, and their interaction on the yield of rainfed rice in Glazoué, Department of Zou-Collines, central Benin between 2010 and 2013. On-farm fertilizer management trials and field surveys were conducted in 13–39 farmers’ fields per year. Field water conditions were visually assessed three times per week during the rice-growing season and flood and drought indices were calculated on the basis of number of days with ponded water and dry surface soil relative to the total number of days for the vegetative, the reproductive and whole rice-growing period. Variations in flood and drought indices were related to the sand content of the soil. While nitrogen was the most limiting nutrient, average response to N fertilizer application was low with an agronomic N use efficiency of only 7–9 kg grain per kg of N applied. Year-to-year variation in rainfall and spatial variation in field water status affected both rice yield and response to N fertilizer. Some 47% of the observed yield variation was explained by field water status and the amounts of N fertilizer applied, with rice response to N fertilizer being less when water was limited. We conclude that the prevailing blanket fertilizer recommendations are unlikely to contribute to yield increases in rainfed systems of West Africa. There is a need for field-specific recommendations that consider soil texture and the spatial–temporal dynamics of water availability.
Abstract
Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 10
19
W/cm
2
), 30 femtosecond, 800 nm high contrast laser ...pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications.
Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted ...whole blood above which the rate of clot formation approaches normal.
Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50–300 mg dl−1 and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls.
Coagulation parameters and platelets were reduced by 74–85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl−1. Adding tissue plasminogen activator, 0.15 μg ml−1, led to a decrease of clot firmness and lysis time.
The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl−1 as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.
PDF
