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541.
Dan K. Kajungu Annette Erhart Ambrose Otau Talisuna Quique Bassat Corine Karema Carolyn Nabasumba Michael Nambozi Halidou Tinto Peter Kremsner Martin Meremikwu Umberto D’Alessandro Niko Speybroeck 《PloS one》2014,9(5)
Background
Pharmacovigilance programmes monitor and help ensuring the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously unknown safety risks is spontaneous notifications. In this study we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria in African children.Methods
We used paediatric safety data from a multi-site, multi-country clinical study conducted in seven African countries (Burkina Faso, Gabon, Nigeria, Rwanda, Uganda, Zambia, and Mozambique). Each site compared three out of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) or chlorproguanil/dapsone and artesunate (CD+A). We examine two pharmacovigilance signal detection methods, namely proportional reporting ratio and Bayesian Confidence Propagation Neural Network on the clinical safety dataset.Results
Among the 4,116 children (6–59 months old) enrolled and followed up for 28 days post treatment, a total of 6,238 adverse events were reported resulting into 346 drug-event combinations. Nine signals were generated both by proportional reporting ratio and Bayesian Confidence Propagation Neural Network. A review of the manufacturer package leaflets, an online Multi-Drug Symptom/Interaction Checker (DoubleCheckMD) and further by therapeutic area experts reduced the number of signals to five. The ranking of some drug-adverse reaction pairs on the basis of their signal index differed between the two methods.Conclusions
Our two data mining methods were equally able to generate suspected signals using the pooled safety data from a phase IIIb/IV clinical trial. This analysis demonstrated the possibility of utilising clinical studies safety data for key pharmacovigilance activities like signal detection and evaluation. This approach can be applied to complement the spontaneous reporting systems which are limited by under reporting. 相似文献542.
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中国洞穴蜘蛛多样性及其对洞穴环境的适应 总被引:1,自引:0,他引:1
对中国洞穴蜘蛛的多样性、地理分布信息进行了详细的闸述.初步探讨了洞穴蜘蛛对洞穴环境的适应性特征及其进化机制.我国洞穴蜘蛛目前已知16科27属80种,其巾暗蛛科、弱蛛科、泰莱蛛科和巨蟹蛛科物种最多;在属级阶元上,以弱蛛属Leptoneta14种、泰莱蛛属Telema lO种、龙角蛛属Draamar如和巾遁蛛属Sinopoda各9种,宽隙蛛属Platocoelotes 8种居多.我国洞穴蜘蛛主要集中分布在贵卅、海南、云南、北京、浙江、广西等喀斯特洞穴较为密集地区,在河北、河南、湖北和湖南也有部分报道.在不同地区分布的洞穴蜘蛛类群或优势类群及区系成分等都存在较大差异.洞穴蜘蛛中约有20%~30%的种类凶为长期生活在黑暗无光、食物匮乏以及缺乏温度和光周期的季节调节等特殊环境,出现了一些地表生境蜘蛛类群中所没有的刘洞穴环境的适应性特征,如缺乏体色素、眼退化共至无眼、附肢延长、全身牛有很多具较敏锐触觉和嗅觉功能的感觉毛、繁殖无季节性、耗氧量降低而新陈代谢缓慢、代谢率降低、产牛的后代少、单个卵粒包含更多的营养等. 相似文献
548.
The objective of this study was to determine the effects of different doses of porcine luteinizing hormone (pLH) versus 100 μg gonadotropin-releasing hormone (GnRH) on ovulatory response (during diestrus and proestrus) and corpus luteum (CL) development in nonlactating cows. In Experiment 1, 75 cows received an intravaginal insert containing 1.9 g progesterone (P4) for 10 d to synchronize estrus (Day 0), with prostaglandin F2α (PGF) at insert removal. On Day 5, all follicles ≥8 mm were ablated, and on Day 12, cows received 8, 12.5, or 25 mg pLH or 100 μg GnRH. Mean (±SEM) plasma P4 concentrations on Day 12 did not differ among treatments (5.6 ± 0.2 ng/mL). Mean plasma LH concentration was greatest (P < 0.01) in cows given 25 mg pLH (4.3 ± 0.4 ng/mL). The ovulatory response to 25 mg pLH (84%) or 100 μg GnRH (72%) was greater (P < 0.05) than that to 8 mg pLH (32%), but not different from that of 12.5 mg pLH (58%). In Experiment 2, 68 cows were given two injections of PGF 10 d apart to synchronize estrus (Day 0). On Day 7, cows received PGF, and, 36 h later, pLH or GnRH (as in Experiment 1). The interval from treatment to ovulation was most variable in cows given 8 mg pLH; only 65% of these cows ovulated during the initial 27 h versus 88% of cows given 25 mg pLH (P < 0.05). Cows given 25 mg pLH or 100 μg GnRH had larger CL area and greater plasma P4 concentrations (P < 0.05) than that of those given 8 mg pLH. In summary, diestrous cows given 25 mg pLH had the greatest plasma luteinizing hormone concentrations, but ovulatory response did not differ from that of those given 100 μg GnRH. Proestrous cows given 25 mg pLH or 100 μg GnRH had greater CL area and P4 concentrations than that of those given 8 mg pLH. 相似文献
549.
Huang SH Long M Wu CH Kwon-Chung KJ Chang YC Chi F Lee S Jong A 《The Journal of biological chemistry》2011,286(40):34761-34769
Cryptococcus neoformans is a neurotropic fungal pathogen, which provokes the onset of devastating meningoencephalitis. We used human brain microvascular endothelial cells (HBMEC) as the in vitro model to investigate how C. neoformans traverses across the blood-brain barrier. In this study, we present several lines of evidence indicating that C. neoformans invasion is mediated through the endocytic pathway via lipid rafts. Human CD44 molecules from lipid rafts can directly interact with hyaluronic acid, the C. neoformans ligand. Bikunin, which perturbs CD44 function in the lipid raft, can block C. neoformans adhesion and invasion of HBMEC. The lipid raft marker, ganglioside GM1, co-localizes with CD44 on the plasma membrane, and C. neoformans cells can adhere to the host cell in areas where GM1 is enriched. These findings suggest that C. neoformans entry takes place on the lipid rafts. Upon C. neoformans engagement, GM1 is internalized through vesicular structures to the nuclear membrane. This endocytic redistribution process is abolished by cytochalasin D, nocodazole, or anti-DYRK3 (dual specificity tyrosine-phosphorylation-regulated kinase 3) siRNA. Concomitantly, the knockdown of DYRK3 significantly reduces C. neoformans invasion across the HBMEC monolayer in vitro. Our data demonstrate that the lipid raft-dependent endocytosis process mediates C. neoformans internalization into HBMEC and that the CD44 protein of the hosts, cytoskeleton, and intracellular kinase-DYRK3 are involved in this process. 相似文献
550.
SarA is an essential positive regulator of Staphylococcus epidermidis biofilm development 总被引:6,自引:0,他引:6
Tormo MA Martí M Valle J Manna AC Cheung AL Lasa I Penadés JR 《Journal of bacteriology》2005,187(7):2348-2356