298 research outputs found

    Plasmin-mediated activation of the coagulation system. :A study of patients with acute ischemic heart disease treated with recombinant tissue-plasminogen activator

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    We have studied the response of haemostatic reaction products in peripheral blood of patients with acute ischaemic heart disease receiving combined recombinant tissue type plasminogen activator/heparin therapy. We have found evidence that formation of excessive amounts of plasmin in vivo in relation to such therapy significantly enhances the degradation of fibrin, and of fibrinogen as well as the formation of thrombin. We conclude that excessive plasmin formation by thrombolytic therapy causes systemic effects including activation of coagulation.</p

    Plasmin-mediated activation of the coagulation system. :A study of patients with acute ischemic heart disease treated with recombinant tissue-plasminogen activator

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    We have studied the response of haemostatic reaction products in peripheral blood of patients with acute ischaemic heart disease receiving combined recombinant tissue type plasminogen activator/heparin therapy. We have found evidence that formation of excessive amounts of plasmin in vivo in relation to such therapy significantly enhances the degradation of fibrin, and of fibrinogen as well as the formation of thrombin. We conclude that excessive plasmin formation by thrombolytic therapy causes systemic effects including activation of coagulation.</p

    Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation

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    Objective-The beneficial effect of dietary fish oil, rich in omega-3 polyunsaturated fatty acids (PUFAs), on cardiovascular disease is multifactorial and may partly rely on their anticoagulant action. We studied how fish oil intake influenced thrombin generation in plasma and which factors were involved herein. Methods and Results-Twenty-five healthy males with borderline overweight received 3.0 g omega-3 PUFAs daily for 4 weeks. Fish oil intake reduced plasma triglycerides and lowered platelet integrin activation, as well as plasma levels of fibrinogen and factor V, but had no effect on vitamin K-dependent coagulation factors. Before fish oil intake, thrombin generation (reflecting the coagulant potential) considerably varied between plasmas from individual subjects, which were partly explained by variation in prothrombin, antithrombin, fibrinogen, and factor V levels. Fish oil intake reduced thrombin generation in the presence and absence of platelets. This reduction correlated with the fish oil effect on fibrinogen and factor V levels. Interestingly, the lowering effect of fish oil on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying a structural fibrinogen α-chain polymorphism. Conclusions-Dietary omega-3 PUFAs provoke a hypocoagulant, vitamin K-independent effect in humans, the degree of which may depend on fibrinogen level. Chemicals / CAS: antithrombin, 9000-94-6; blood clotting factor 5, 9001-24-5, 9013-23-4; cholesterol, 57-88-5; fibrinogen, 9001-32-5; fish oil, 8016-13-5; protein C, 60202-16-6; prothrombin, 9001-26-7; thrombin, 9002-04-4; vitamin K group, 12001-79-5; Cholesterol, LDL; Factor V, 9001-24-5; Fatty Acids, Omega-3; Fibrinogen, 9001-32-5; Fish Oils; Peptide Fragments; Thrombin, 3.4.21.5; Triglycerides; thrombin receptor peptide (42-47

    New Development in Chip Control Research: Moving Towards Chip Breakability Predictions for Un-manned Manufacture

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    In the over-broken and effectively broken ranges, as the ratio increases, the radius of the chip also increases. However, in the region where tangled chips are produced the trend reverses itself. In this region, the chip radius decreases as the ratio increases. The results regarding the chip radius are interesting, but they do not provide much useful information for the machine operator who needs to know where to place a chip breaker to effectively control chips in a turning operation. In order to make the graph useful for this purpose, it has been broken down into three distinct regions by two vertical dashed line. The first line is located at the point where the ratio of breaker location to feed equals 13.5. To the left of this line the chips are over-broken. The second line is located at the point where the ratio is 29.5. To the right of this line the chips are all underbroken. Between these lines lies the region where effective breakage was noted. The transitions from one type of chip to another are very distinct. This indicates that the ratio of breaker location to feed is a good measure for predicting and adjusting breaker location for proper chip control when turning 4150 steel. Conclusions The data collected for this investigation indicates that it is possible to provide a practical means for a machine operator to predict where an obstruction type chip breaker should be placed for effective chip control when working with 4150 steel. The location of the breaker can be calculated using a ratio of breaker location to the feed which results in well-broken chips. Since the feed will have been set and is known to the operator, the proper breaker location can be calculated by multiplying the feed by the proper ratio. A good value of this ratio appears to be about 20, so for effective chip breaking with 4150 steel, the breaker should be located back from the primary cutting edge by a distance 20 times the feed. The beauty of this method is that the main cutting parameters need not be changed to get good chips. This means chip control is possible without decreasing the efficiency of the process significantly. These experimental results also agree with the analysis in the sense that the ratio of the feed to the location of the chip breaker is indeed the most important parameter. The optimal ratio of chip breaker location to feed may also depend on other parameters such as tool geometry and materials as these variables affect the cutting process. However, for a given tool geometry and materials, properly broken chips can be obtained over various machining conditions by maintaining the ratio at a constant value

    C-reactive protein reference percentiles among pre-adolescent children in Europe based on the IDEFICS study population

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    OBJECTIVES: C-reactive protein (CRP) is involved in a wide range of diseases. It is a powerful marker for inflammatory processes used for diagnostic and monitoring purposes. We aimed to establish reference values as data on the distribution of serum CRP levels in young European children are scarce. SUBJECTS: Reference values of high-sensitivity CRP concentrations were calculated for 9855 children aged 2.0-10.9 years, stratified by age and sex. The children were recruited during the population-based European IDEFICS study (Identification and prevention of Dietary-and lifestyle-induced health Effects in Children and infantS) with 18 745 participants recruited from 2007 to 2010. RESULTS: In 44.1 % of the children, CRP values were below or equal the detection limit of 0.2 mg/l. Median CRP concentrations showed a slight negative age trend in boys and girls, whereas serum CRP values were slightly higher in girls than in boys across all age groups. CONCLUSIONS: Our population-based reference values of CRP may guide paediatric practice as elevated values may require further investigation or treatment. Therefore, the presented reference values represent a basis for clinical evaluation and for future research on risk assessment of diseases associated with increased CRP levels among children

    Effects of vertical grid spacing on the climate simulated in the ICON-Sapphire global storm-resolving model

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    Global storm-resolving models (GSRMs) use strongly refined horizontal grids compared with the climate models typically used in the Coupled Model Intercomparison Project (CMIP) but employ comparable vertical grid spacings. Here, we study how changes in the vertical grid spacing and adjustments to the integration time step affect the basic climate quantities simulated by the ICON-Sapphire atmospheric GSRM. Simulations are performed over a 45 d period for five different vertical grids with between 55 and 540 vertical layers and maximum tropospheric vertical grid spacings of between 800 and 50 m, respectively. The effects of changes in the vertical grid spacing are compared with the effects of reducing the horizontal grid spacing from 5 to 2.5 km. For most of the quantities considered, halving the vertical grid spacing has a smaller effect than halving the horizontal grid spacing, but it is not negligible. Each halving of the vertical grid spacing, along with the necessary reductions in time step length, increases cloud liquid water by about 7 %, compared with an approximate 16 % decrease for halving the horizontal grid spacing. The effect is due to both the vertical grid refinement and the time step reduction. There is no tendency toward convergence in the range of grid spacings tested here. The cloud ice amount also increases with a refinement in the vertical grid, but it is hardly affected by the time step length and does show a tendency to converge. While the effect on shortwave radiation is globally dominated by the altered reflection due to the change in the cloud liquid water content, the effect on longwave radiation is more difficult to interpret because changes in the cloud ice concentration and cloud fraction are anticorrelated in some regions. The simulations show that using a maximum tropospheric vertical grid spacing larger than 400 m would increase the truncation error strongly. Computing time investments in a further vertical grid refinement can affect the truncation errors of GSRMs similarly to comparable investments in horizontal refinement, because halving the vertical grid spacing is generally cheaper than halving the horizontal grid spacing. However, convergence of boundary layer cloud properties cannot be expected, even for the smallest maximum tropospheric grid spacing of 50 m used in this study.</p

    Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects.

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    To identify the genomic regions that confer risk and protection for major depressive disorder (MDD) in humans, large-scale studies are needed. Such studies should collect multiple phenotypes, DNA, and ideally, biological material that allows gene expression analysis, transcriptomic, proteomic, and metabolomic studies. In this paper, we briefly review linkage studies of MDD and then describe the large-scale nationwide biological sample collection in Dutch twin families from the Netherlands Twin Register (NTR) and in participants in the Netherlands Study of Depression and Anxiety (NESDA). Within these studies, 1862 participants with a diagnosis of MDD and 1857 controls at low liability for MDD have been selected for genome-wide genotyping by the US Foundation for the National Institutes of Health Genetic Association Information Network. Stage 1 genome-wide association results are scheduled to be accessible before the end of 2007. Genome-wide association results are open-access and can be viewed at the dbGAP web portal (http://www.ncbi.nlm.nih.gov). Approved users can download the genotype and phenotype data, which have been made available as of 9 October 2007

    DNA methylation signatures of aggression and closely related constructs : A meta-analysis of epigenome-wide studies across the lifespan

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    DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.Peer reviewe

    DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

    Get PDF
    DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.</p
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