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21.
Verena I. Carrara Khin Maung Lwin Aung Pyae Phyo Elizabeth Ashley Jacher Wiladphaingern Kanlaya Sriprawat Marcus Rijken Machteld Boel Rose McGready Stephane Proux Cindy Chu Pratap Singhasivanon Nicholas White Fran?ois Nosten 《PLoS medicine》2013,10(3)
Background
The Shoklo Malaria Research Unit has been working on the Thai–Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.Methods and Findings
Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76–80) (1,048/1,344 consultations) to 7% (95% CI 6.2–7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3–1.4) to 0.7 (95% CI 0.7–0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04–0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0–28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8–4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20–62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13–45) (8/29 patients) in 2011.Conclusions
Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai–Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors'' Summary 相似文献22.
Philippe Barthe Brice Murciano Theo Schetters André Gorenflot Stephane Delbecq Christian Roumestand 《Biomolecular NMR assignments》2013,7(2):241-244
We report here the resonance assignment of EDK-?-Bd37, conformational mutant potentially displaying the “open” conformation of Bd37, a 25 kDa surface protein from the Apicomplexa parasite Babesia divergens that could undergo drastic conformational changes during erythrocyte invasion. 相似文献
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Stephane Savanah 《Biology & philosophy》2013,28(4):657-673
The view that mirror self-recognition (MSR) is a definitive demonstration of self-awareness is far from universally accepted, and those who do support the view need a more robust argument than the mere assumption that self-recognition implies a self-concept (e.g. Gallup in Socioecology and Psychology of Primates, Mouton, Hague, 1975; Gallup and Suarez in Psychological Perspectives on the Self, vol 3, Erlbaum, Hillsdale, 1986). In this paper I offer a new argument in favour of the view that MSR shows self-awareness by examining the nature of the mirror image itself. I argue, using the results of ‘symbol-mindedness’ experiments by Deloache (Trends Cogn Sci 8(2):66–70, 2004), that where self-recognition exists, the mirror image must be functioning as a symbol from the perspective of the subject and the subject must therefore be ‘symbol-minded’ and hence concept possessing. Further to this, according to the Concept Possession Hypothesis of Self-Consciousness (Savanah in Conscious Cogn 2011), concept possession alone is sufficient to demonstrate the existence of self-awareness. Thus MSR as a demonstration of symbol-mindedness implies the existence of self-awareness. I begin by defending the ‘mark test’ protocol as a robust methodology for determining self-recognition. Then follows a critical examination of the extreme views both for and against the interpretation of MSR as an indication of self-awareness: although the non-mentalistic interpretation of MSR is unconvincing, the argument presented by Gallup is also inadequate. I then present the symbol-mindedness argument to fill in the gaps in the Gallup approach. 相似文献
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Devarsetty?PraveenEmail author Anushka?Patel Stephen?McMahon Dorairaj?Prabhakaran Gari?D.?Clifford Pallab?K.?Maulik Rohina?Joshi Stephen?Jan Stephane?Heritier David?Peiris 《Implementation science : IS》2013,8(1):137
Background
Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed.Methods
We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension’s region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation.Expected outcomes
The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations.Significance
The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings.Trial registration
Clinical Trial Registry India CTRI/2013/06/003753.27.
Muhammad A. Javed Somayyeh Poshtiban Denis Arutyunov Stephane Evoy Christine M. Szymanski 《PloS one》2013,8(7)
Campylobacter jejuni and Campylobacter coli are the most common bacterial causes of foodborne gastroenteritis which is occasionally followed by a debilitating neuropathy known as Guillain-Barré syndrome. Rapid and specific detection of these pathogens is very important for effective control and quick treatment of infection. Most of the diagnostics available for these organisms are time consuming and require technical expertise with expensive instruments and reagents to perform. Bacteriophages bind to their host specifically through their receptor binding proteins (RBPs), which can be exploited for pathogen detection. We recently sequenced the genome of C. jejuni phage NCTC12673 and identified its putative host receptor binding protein, Gp047. In the current study, we localized the receptor binding domain to the C-terminal quarter of Gp047. CC-Gp047 could be produced recombinantly and was capable of agglutinating both C. jejuni and C. coli cells unlike the host range of the parent phage which is limited to a subset of C. jejuni isolates. The agglutination procedure could be performed within minutes on a glass slide at room temperature and was not hindered by the presence of buffers or nutrient media. This agglutination assay showed 100% specificity and the sensitivity was 95% for C. jejuni (n = 40) and 90% for C. coli (n = 19). CC-Gp047 was also expressed as a fusion with enhanced green fluorescent protein (EGFP). Chimeric EGFP_CC-Gp047 was able to specifically label C. jejuni and C. coli cells in mixed cultures allowing for the detection of these pathogens by fluorescent microscopy. This study describes a simple and rapid method for the detection of C. jejuni and C. coli using engineered phage RBPs and offers a promising new diagnostics platform for healthcare and surveillance laboratories. 相似文献
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Aurine Verkest Stephane Bourout Jurgen Debaveye Kristine Reynaert Bernadette Saey Ilse Van den Brande Kathleen D'Halluin 《Plant biotechnology journal》2019,17(7):1236-1247
Targeted Genome Optimization (TGO) using site‐specific nucleases to introduce a DNA double‐strand break (DSB) at a specific target locus has broadened the options available to breeders for generation and combination of multiple traits. The use of targeted DNA cleavage in combination with homologous recombination (HR)‐mediated repair, enabled the precise targeted insertion of additional trait genes (2mepsps, hppd, axmi115) at a pre‐existing transgenic locus in cotton. Here we describe the expression and epigenome analyses of cotton Targeted Sequence Insertion (TSI) events over generations. In a subset of events, we observed variability in the level of transgene (hppd, axmi115) expression between independent but genetically identical TSI events. Transgene expression could also be differential within single events and variable over generations. This expression variability and silencing occurred independently of the transgene sequence and could be attributed to DNA methylation that was further linked to different DNA methylation mechanisms. The trigger(s) of transgene DNA methylation remains elusive but we hypothesize that targeted DSB induction and repair could be a potential trigger for DNA methylation. 相似文献
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