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21.
Studies on leadership have focused either on physiological state as the key predictor (i.e. "leading according to need"), or else on temperamental asymmetries among group members (i.e. intrinsic leadership). In this paper, we explore how both factors interact in determining the emergence of leaders. We observed pairs of sticklebacks with varying degrees of temperamental difference, and recorded their movements back and forth between a safe covered area and a risky foraging area, both before and after satiating one of the two pair members (but not the other). Before satiation, when the fish had similar hunger levels, temperament was a good predictor of social roles, with the bolder member of a pair leading and the shyer member following. The effect of satiation depended on which fish received the additional food. When the shyer member of a pair was fed, and consequently became less active, the bolder fish did not change its behaviour but continued to lead. By contrast, when the bolder member of a pair was fed, and consequently initiated fewer trips out of cover, the shyer partner compensated by initiating trips more frequently itself. In pairs that differed only a little in temperament, feeding the bolder fish actually led to a role reversal, with the shyer fish emerging as a leader in the majority of joint trips out of cover. Our results show that leadership emerges as the consequence of multiple factors, and that their interaction can be complex. 相似文献
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Hailu A Musa A Wasunna M Balasegaram M Yifru S Mengistu G Hurissa Z Hailu W Weldegebreal T Tesfaye S Makonnen E Khalil E Ahmed O Fadlalla A El-Hassan A Raheem M Mueller M Koummuki Y Rashid J Mbui J Mucee G Njoroge S Manduku V Musibi A Mutuma G Kirui F Lodenyo H Mutea D Kirigi G Edwards T Smith P Muthami L Royce C Ellis S Alobo M Omollo R Kesusu J Owiti R Kinuthia J;Leishmaniasis East Africa Platform 《PLoS neglected tropical diseases》2010,4(10):e709
Background
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.Methods
This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment.Findings
Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified.Conclusion
The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies. 相似文献24.
Musa AM Younis B Fadlalla A Royce C Balasegaram M Wasunna M Hailu A Edwards T Omollo R Mudawi M Kokwaro G El-Hassan A Khalil E 《PLoS neglected tropical diseases》2010,4(10):e855
Background
A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.Methods
This randomized, open-label, dose-finding, phase II study assessed the two above high-dose PM treatment regimens. Patients with clinical features and positive bone-marrow aspirates for VL were enrolled. All patients received their assigned courses of PM intramuscularly and adverse events were monitored. Parasite clearance in bone-marrow aspirates was tested by microscopy at end of treatment (EOT, primary efficacy endpoint), 3 months (in patients who were not clinically well) and 6 months after EOT (secondary efficacy endpoint). Pharmacokinetic data were obtained from a subset of patients weighing over 30 kg.Findings
42 patients (21 per group) aged between 4 and 60 years were enrolled. At EOT, 85% of patients (95% confidence interval [CI]: 63.7% to 97.0%) in the 20 mg/kg/day group and 90% of patients (95% CI: 69.6% to 98.8%) in the 15 mg/kg/day group had parasite clearance. Six months after treatment, efficacy was 80.0% (95% CI: 56.3% to 94.3%) and 81.0% (95% CI: 58.1% to 94.6%) in the 20 mg/kg/day and 15 mg/kg/day groups, respectively. There were no serious adverse events. Pharmacokinetic profiles suggested a difference between the two doses, although numbers of patients recruited were too few to make it significant (n = 3 and n = 6 in the 20 mg/kg/day and 15 mg/kg/day groups, respectively).Conclusion
Data suggest that both high dose regimens were more efficacious than the standard 15 mg/kg/day PM for 21 days and could be further evaluated in phase III studies in East Africa.Trial Registration
ClinicalTrials.gov NCT00255567相似文献25.
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Sungwon Jeon Asta Blazyte Changhan Yoon Hyojung Ryu Yeonsu Jeon Youngjune Bhak Dan Bolser Andrea Manica Eun-Seok Shin Yun Sung Cho Byung Chul Kim Namhee Ryoo Hansol Choi Jong Bhak 《Molecules and cells》2021,44(9):680
Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing. 相似文献
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Prugnolle F Manica A Charpentier M Guégan JF Guernier V Balloux F 《Current biology : CB》2005,15(11):1022-1027
The human leukocyte antigen (HLA; known as MHC in other vertebrates) plays a central role in the recognition and presentation of antigens to the immune system and represents the most polymorphic gene cluster in the human genome [1]. Pathogen-driven balancing selection (PDBS) has been previously hypothesized to explain the remarkable polymorphism in the HLA complex, but there is, as yet, no direct support for this hypothesis [2 and 3]. A straightforward prediction coming out of the PDBS hypothesis is that populations from areas with high pathogen diversity should have increased HLA diversity in relation to their average genomic diversity. We tested this prediction by using HLA class I genetic diversity from 61 human populations. Our results show that human colonization history explains a substantial proportion of HLA genetic diversity worldwide. However, between-population variation at the HLA class I genes is also positively correlated with local pathogen richness (notably for the HLA B gene), thus providing support for the PDBS hypothesis. The proportion of variations explained by pathogen richness is higher for the HLA B gene than for the HLA A and HLA C genes. This is in good agreement with both previous immunological and genetic data suggesting that HLA B could be under a higher selective pressure from pathogens. 相似文献
28.
van den Broek I Amsalu R Balasegaram M Hepple P Alemu E Hussein el B Al-Faith M Montgomery J Checchi F 《Malaria journal》2005,4(1):14-7
Background
The treatment for Plasmodium falciparum malaria in Sudan has been in process of change since 2003. Preceding the change, this study aimed to determine which artemisinin-based combination therapies is more effective to treat uncomplicated malaria in Malakal, Upper Nile, Sudan.Methods
Clinical trial to assess the efficacy of 2 antimalarial therapies to treat P. falciparum infections in children aged 6–59 months, in a period of 42 days after treatment.Results
A total of 269 children were followed up to 42 days. Artesunate plus Sulfadoxine/Pyrimethamine (AS+SP) and Artesunate plus Amodiaquine (AS+AQ) were both found to be efficacious in curing malaria infections by rapid elimination of parasites and clearance of fever, in preventing recrudescence and suppressing gametocytaemia. The combination of AS+SP appeared slightly more efficacious than AS+AQ, with 4.4% (4/116) versus 15% (17/113) of patients returning with malaria during the 6-week period after treatment (RR = 0.9, 95% CI 0.81–0.96). PCR analysis identified only one recrudescence which, together with one other early treatment failure, gave efficacy rates of 99.0% for AS+AQ (96/97) and 99.1% for AS+SP (112/113). However, PCR results were incomplete and assuming part of the indeterminate samples were recrudescent infections leads to an estimated efficacy ranging 97–98% for AS+SP and 88–95% for AS+AQ.Conclusion
These results lead to the recommendation of ACT, and specifically AS+SP, for the treatment of uncomplicated falciparum malaria in this area of Sudan. When implemented, ACT efficacy should be monitored in sentinel sites representing different areas of the country. 相似文献29.
Atapour Amir Negahdaripour Manica Ghasemi Younes Razmjuee Dorna Savardashtaki Amir Mousavi Seyyed Mojtaba Hashemi Seyyed Alireza Aliabadi Ali Nezafat Navid 《International journal of peptide research and therapeutics》2020,26(1):369-380
International Journal of Peptide Research and Therapeutics - Breast cancer (BC) is the most common type of women’s cancer with a prevalence of about 25%, although it is rare in men... 相似文献
30.
Sakib Burza Prabhat K. Sinha Raman Mahajan María Angeles Lima Gaurab Mitra Neena Verma Manica Balsegaram Pradeep Das 《PLoS neglected tropical diseases》2014,8(1)