1,721,851 research outputs found
Maximum-Likelihood Symbol Timing Estimation Algorithm for OFDM Systems Based on a Repeated Preamble
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Global coconut research for development programme (PROCORD)
This paper deals with the genesis of PROCORD, goals and objectives priority research areas, proposed organizational structure, programme coordination and meetings. The original proposal made by BUROTROP and COGENT for the establishment of a global coconut research programme along the commodity chain approach was well received by the representatives from 34 coconut producing countries who attended the COCOTECH meeting in Chennai, India in July 2000. This meeting recommended that a well-coordinated and well-supported coconut global research programme be developed along the commodity chain approach to address the research areas that seriously limit coconut productivity and income. Research priority areas have been identified which are subject to periodical changes as needed. The coordination of PROCORD will be performed by a committee comprising the Chair and Executive Director of APCC; the Chair of the Board of Administrators and Executive Director of BUROTROP; and the Chair of the COGENT Steering Committee and the COGENT Coordinator, Six research and development programmes have been assigned to APCC, BURTOTROP and COGENT as their lead responsibilities. Under this COGENT will handle Genetic Resources and Improvement and Socio-economics and Policy Support; BUROTROP will handle Agronomy and Coconut Based Farming Systems and Crop Protection; and APCC will deal with Processing and Marketing
Activated prothrombin complex concentrate (APCC)-mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness.
BACKGROUND AND OBJECTIVES: Activated prothrombin complex concentrates (APCCs), utilized in bypassing therapy for hemophiliacs with inhibitor, contain factors (Fs) VII, FII, FIX and FX, and their active forms. A recent report has demonstrated that mixtures of APCC and FVIII potentiated thrombin generation, in vitro, in plasma from patients with severe hemophilia A, but the mechanism(s) involved remains unknown.
RESULTS: APCC (0.05 U mL(-1) ) increased FVIII activity ~ 4-fold within 1 min in one-stage clotting assays, followed by a return to initial levels within 10 min. This reaction was dependent on the presence of tissue factor and phospholipid. Thrombin generation produced from APCC was ~ 3.5-fold greater in the presence of FVIII than that in its absence. SDS-PAGE analysis revealed that APCC sequentially proteolyzed the heavy chain of FVIII at Arg(372) and Arg(740) , followed by cleavage at Arg(336) . Proteolysis was prevented by FVIIa inhibitor, but not by hirudin, supporting the concept that APCC itself possessed the potential to activate FVIII in early coagulation phases, and that FVIIa in APCC contributed mainly to this reaction. APCC-mediated FVIII activation was unaffected by the addition of anti-FVIII inhibitor antibodies, irrespective of epitope specificity. Anti-C2 type 1 inhibitors, however, diminished the inactivation phase of the APCC reaction by inhibiting cleavage at Arg(336) .
CONCLUSION: Small amounts of APCC, relative to the standard concentration used for clinical purposes, could activate FVIII directly, even in the presence of anti-FVIII antibodies. Combination therapy based on mixtures of APCC and FVIII could have significant beneficial implications for the treatment of hemophilia A patients with inhibitors.博士(医学)・甲第601号・平成25年7月22日© 2013 International Society on Thrombosis and Haemostasis
Activated prothrombin complex concentrate (APCC)-mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness.
BACKGROUND AND OBJECTIVES: Activated prothrombin complex concentrates (APCCs), utilized in bypassing therapy for hemophiliacs with inhibitor, contain factors (Fs) VII, FII, FIX and FX, and their active forms. A recent report has demonstrated that mixtures of APCC and FVIII potentiated thrombin generation, in vitro, in plasma from patients with severe hemophilia A, but the mechanism(s) involved remains unknown.
RESULTS: APCC (0.05 U mL(-1) ) increased FVIII activity ~ 4-fold within 1 min in one-stage clotting assays, followed by a return to initial levels within 10 min. This reaction was dependent on the presence of tissue factor and phospholipid. Thrombin generation produced from APCC was ~ 3.5-fold greater in the presence of FVIII than that in its absence. SDS-PAGE analysis revealed that APCC sequentially proteolyzed the heavy chain of FVIII at Arg(372) and Arg(740) , followed by cleavage at Arg(336) . Proteolysis was prevented by FVIIa inhibitor, but not by hirudin, supporting the concept that APCC itself possessed the potential to activate FVIII in early coagulation phases, and that FVIIa in APCC contributed mainly to this reaction. APCC-mediated FVIII activation was unaffected by the addition of anti-FVIII inhibitor antibodies, irrespective of epitope specificity. Anti-C2 type 1 inhibitors, however, diminished the inactivation phase of the APCC reaction by inhibiting cleavage at Arg(336) .
CONCLUSION: Small amounts of APCC, relative to the standard concentration used for clinical purposes, could activate FVIII directly, even in the presence of anti-FVIII antibodies. Combination therapy based on mixtures of APCC and FVIII could have significant beneficial implications for the treatment of hemophilia A patients with inhibitors.博士(医学)・甲第601号・平成25年7月22日© 2013 International Society on Thrombosis and Haemostasis.identifier:Journal of thrombosis and haemostasis Vol.11 No.5 p.902-910identifier:15387933identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2635identifier:Journal of thrombosis and haemostasis, 11(5): 902-91
ROTEM and vitro reversal of warfarin with APCC
Background: Warfarin-treated patients with a prolonged Prothrombin Time (PT) can have a normal rotational thromboelastometry (ROTEM) clotting time (CT). A previous in vitro study found that activated prothrombin complex concentrates (APCC) could reverse an albumin-induced coagulopathy monitored with ROTEM, but that prothrombin complex concentrates (PCC) could not. The aim of this study was to investigate the ability of ROTEM to monitor the in vitro reversal of warfarin-induced coagulopathy using APCC and to define an APCC dose response. Method: During the routine control of PT in 27 patients treated with warfarin, one extra 4.5 ml test tube of citrated whole blood was retrieved. Two concentrations of tissue factor ROTEM tissue factor (TF) activating reagents were used: a standard ROTEM ExTEM and a diluted 1:19000 concentration. The effects of two separate doses of APCC added in vitro corresponding to in vivo doses of 50 IE or 100 IE/kg were then studied on the ROTEM. Results: The ROTEM EXTEM CT was prolonged beyond the upper normal range of 68 s in patients with PT >3.0, with a correlation coefficient of 0.88 to PT. ROTEM with the ExTEM reagent alongside high and low doses of APCC resulted in a significant shortening of median CT, both compared to baseline (100 s) and after low (65 s) and high doses (57 s). This was most evident in patients with PT >2.0. ROTEM signals of clot propagation to clot formation time (CFT) and α angle had the reverse pattern. There was no effect on maximal clot strength with APCC. With the diluted TF no CT shortening was found with APCC. Conclusion: A clear dose response of APCC added in vitro to correct the effects of warfarin on ROTEM EXTEM CT was verified. ROTEM CT should be tested with non-activated PCC for in vivo reversal of warfarin in patients along with verification of a normalised PT. Further studies are needed to verify if a ROTEM CT in the lower normal range of <57-65 s, as found in our in vitro APCC-spiked warfarin blood, is safe for invasive procedures
Global coconut research for development programme progress and prospects
Under PROCORD, COGENT is mandated to coordinate research on genetic resources and improvement and on soscioeconomics and policy support. COGENT has conserved and characterized 1402 accessions in genebanks in 23 countries and 224 accessions in COGENT's multi-site International Coconut Genebank. It is developing long-term storage techniques on cryopreservation and has initiated in situ/on-farm conservation in eight countries. It is conducting multilocation trials of 34 promising hybrids in four African and three LAC countries; developed a microsatellite molecular marker kit in collaboration with CIRAD and BUROTROP, trained researchers from nine countries and provided research grants to each trainee to use this technique in characterizing their genetic diversity. An ADB-funded "Poverty reduction in coconut growing communities" has been initiated in 24 project sites in eight countries. COGENT has supported the MSc scholarships of 10 coconut researchers who have all graduated and two more PhD scholarships are ongoing. COGENT has identified two initial priority projects to implement under PROCORD: 1) Establishment and strengthening of the multi-site International Coconut Genebank and 2) "Poverty reduction in coconut growing communities" to demonstrate that coconut farmers need not be poor. BUROTROP has been active in the development of PROCORD and its promotion to European funding agencies and institutions, under PROCORD, BUROTROP is mandated to coordinate research on agronomy, physiology and coconut-based agroforestry systems and crop protection. Two urgent priorities have been identified in two research areas assigned to BUROTROP: tolerance to drought in coconut and management of coconut Lethal Yellowing Disease and is developing proposals to address these priorities and coordinating with other initiatives in these two themes. Under PROCORD, APCC is mandated to coordinate research on processing and marketing. APCC collected information on availability of copra driers and small coconut oil crushing mills. APCC has participated in the International Food Ingredients Exhibition in Bangkok and in the International Coconut Summit and Exhibition in India; in several other international and national seminars and promoted the health and nutritional benefits of coconut products. Project proposal formulation is being undertaken to develop a mechanical harvester, dehusker, refinement of technology for desiccated coconuts and to develop technologies for making niche products for coconut, formulate quality standards of coconut products including virgin oil, assess the nutritive effects as well as health effects of coconut against viral diseases. Preliminary information on availability of products in Europe and USA markets are being obtained. Studies to identify market potential and access and domestic coconut use need to be undertaken. An integrated project on processing and marketing is also being formulated
Thrombus score and thrombus weight: Dose-response for 4F-PCC, aPCC, and rFVIIa.
(A) 4F-PCC thrombus score; (B) 4F-PCC thrombus weight; (C) aPCC thrombus score; (D) aPCC thrombus weight; (E) rFVIIa thrombus score; (F) rFVIIa thrombus weight. Data for venous stasis-induced thrombosis 10 minutes after the end of PCC, aPCC or rFVIIa infusion. Figure shows mean (standard deviation). * indicates a therapeutic dose.</p
SAFETY AND EFFECTIVENESS OF ACTIVATED PROTHROMBIN COMPLEX CONCENTRATE (APCC) MONOTHERAPY IN PATIENTS WITH HEMOPHILIA AND INHIBITORS (PWHI) UNDERGOING SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Introduction: Control of hemostasis during and after surgical procedures in PwHI is challenging. aPCC (Feiba®, Baxalta Inc, a Takeda company, Lexington, MA, USA), a bypassing agent, is indicated for patients with congenital hemophilia A or B with inhibitors for on-demand, prophylaxis and perioperative management, and for acquired hemophilia patients. We present a systematic literature review of studies reporting aPCC safety and a meta-analysis of the hemostatic effectiveness of aPCC monotherapy during major and minor surgical procedures in PwHI.
Methods: This systematic review and meta-analysis was carried out in MedLine through Pubmed from January 1, 1980 (aPCC inception) to June 30, 2018. Prospective, retrospective, randomized and non-randomized studies that reported the safety and hemostatic effectiveness of aPCC monotherapy in PwHI during surgery were eligible. Studies investigating concomitant/sequential infusion of aPCC with rFVIIa, tranexamic acid or emicizumab were excluded. Safety outcomes included serious adverse events (SAEs), including thromboembolic event (TEE), thrombotic microangiopathy (TMA), and other AEs associated with aPCC monotherapy. The hemostatic effectiveness was assessed intraoperatively by the surgeon and late postoperatively by the hematologist and rated as “excellent, good, fair or poor”.
Results: Of 645 publications describing aPCC as monotherapy in PwHI, 14 publications (including 158 patients) reported aPCC monotherapy in a surgical setting (100 major and 162 minor surgeries). TEE occurrence was reported in 4 major surgeries in 4 patients. One SAE of a clot in an arteriovenous fistula (possibly-related to aPCC) was reported. No reports of TMAs were identified in publications of studies that used aPCC as monotherapy. The proportion (95% confidence interval, CI) of major procedures in which hemostatic effectiveness was rated as excellent/good was 0.91 [(0.83-0.99); p=0.04 for heterogeneity] and for minor procedures this was 0.98 [(0.95-1.00); p=0.86 for heterogeneity].
Discussion/Conclusion: In this analysis of published studies involving patients treated with aPCC monotherapy in a surgical setting, a low rate of TEE occurrence and no TMAs were reported, while the hemostatic effectiveness of aPCC monotherapy was rated as excellent/good in >90% of both minor and major surgical procedures
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