19 research outputs found

    Limits to scale invariance in alluvial rivers

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    Assumptions about fluvial processes and process–form relations are made in general models and in many site‐specific applications. Many standard assumptions about reach‐scale flow resistance, bed‐material entrainment thresholds and transport rates, and downstream hydraulic geometry involve one or other of two types of scale invariance: a parameter (e.g. critical Shields number) has the same value in all rivers, or doubling one variable causes a fixed proportional change in another variable in all circumstances (e.g. power‐law hydraulic geometry). However, rivers vary greatly in size, gradient, and bed material, and many geomorphologists regard particular types of river as distinctive. This review examines the tension between universal scaling assumptions and perceived distinctions between different types of river. It identifies limits to scale invariance and departures from simple scaling, and illustrates them using large data sets spanning a wide range of conditions. Scaling considerations and data analysis support the commonly made distinction between coarse‐bed and fine‐bed reaches, whose different transport regimes can be traced to the different settling‐velocity scalings for coarse and fine grains. They also help identify two end‐member sub‐types: steep shallow coarse‐bed ‘torrents’ with distinctive flow‐resistance scaling and increased entrainment threshold, and very large, low‐gradient ‘mega rivers’ with predominantly suspended load, subdued secondary circulation, and extensive backwater conditions

    Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: user acceptability

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    <p>Abstract</p> <p>Background</p> <p>Malaria in pregnancy is associated with increased risks of maternal and foetal complications. Currently, intermittent preventive treatment (IPT) of malaria during pregnancy with sulphadoxine-pyrimethamine (SP) is recommended by the WHO as part of a package of interventions also including insecticide-treated nets and effective case management. However, with increasing resistance to SP, the effectiveness of SP-IPT has been questioned. A randomized controlled trial (RCT) to investigate the relative efficacy of an alternative strategy of intermittent screening and treatment (IST), which involves a rapid diagnostic test for malaria at scheduled ANC visits and treatment of women only if positive, versus SP-IPT has been conducted in Ashanti region, Ghana. This paper reports on a complementary study investigating the acceptability of the different strategies to women enrolled in the trial.</p> <p>Methods</p> <p>Data were collected through twelve focus group discussions with women selected at random from the different arms of the RCT, exploring their experiences and perceptions about antenatal care and their involvement in the trial. Content analysis was used to identify relevant themes to structure the results.</p> <p>Results</p> <p>Five main themes emerged from participants' experiences of ANC and the RCT that would influence their acceptability of malaria prevention strategies during pregnancy: health benefits; drugs received; tests received; other services received; and health worker attitude. Their own health and that of their baby were strong motivations for attending ANC, and reported favourably as an outcome of being in the RCT. Women were not always clear on the biomedical function of drugs or blood tests but generally accepted them due to strong trust in the health staff. Home visits by staff and free ITNs as part of the trial were appreciated. Politeness and patience of health staff was a very strong positive factor.</p> <p>Conclusions</p> <p>Overall, both intermittent screening and treatment and intermittent preventive treatment appeared equally acceptable to pregnant women as strategies for the control of malaria in pregnancy. The women were more concerned about quality of services received, in particular the polite and patient attitude of health staff, and positive health implications for themselves and their babies than about the nature of the intervention.</p

    Down-Regulation of miR-101 in Endothelial Cells Promotes Blood Vessel Formation through Reduced Repression of EZH2

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    Angiogenesis is a balanced process controlled by pro- and anti-angiogenic molecules of which the regulation is not fully understood. Besides classical gene regulation, miRNAs have emerged as post-transcriptional regulators of angiogenesis. Furthermore, epigenetic changes caused by histone-modifying enzymes were shown to modulate angiogenesis as well. However, a possible interplay between miRNAs and histone-modulating enzymes during angiogenesis has not been described. Here we show that VEGF-mediated down-regulation of miR-101 caused pro-angiogenic effects. We found that the pro-angiogenic effects are partly mediated through reduced repression by miR-101 of the histone-methyltransferase EZH2, a member of the Polycomb group family, thereby increasing methylation of histone H3 at lysine 27 and transcriptome alterations. In vitro, the sprouting and migratory properties of primary endothelial cell cultures were reduced by inhibiting EZH2 through up-regulation of miR-101, siRNA-mediated knockdown of EZH2, or treatment with 3-Deazaneplanocin-A (DZNep), a small molecule inhibitor of EZH2 methyltransferase activity. In addition, we found that systemic DZNep administration reduced the number of blood vessels in a subcutaneous glioblastoma mouse model, without showing adverse toxicities. Altogether, by identifying a pro-angiogenic VEGF/miR-101/EZH2 axis in endothelial cells we provide evidence for a functional link between growth factor-mediated signaling, post-transcriptional silencing, and histone-methylation in the angiogenesis process. Inhibition of EZH2 may prove therapeutic in diseases in which aberrant vascularization plays a role

    Population-scale analysis of common and rare genetic variation associated with hearing loss in adults

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    To better understand the genetics of hearing loss, we performed a genome-wide association meta-analysis with 125,749 cases and 469,497 controls across five cohorts. We identified 53/c loci affecting hearing loss risk, including common coding variants in COL9A3 and TMPRSS3. Through exome sequencing of 108,415 cases and 329,581 controls, we observed rare coding associations with 11 Mendelian hearing loss genes, including additive effects in known hearing loss genes GJB2 (Gly12fs; odds ratio [OR] = 1.21, P = 4.2 × 10-11) and SLC26A5 (gene burden; OR = 1.96, P = 2.8 × 10-17). We also identified hearing loss associations with rare coding variants in FSCN2 (OR = 1.14, P = 1.9 × 10-15) and KLHDC7B (OR = 2.14, P = 5.2 × 10-30). Our results suggest a shared etiology between Mendelian and common hearing loss in adults. This work illustrates the potential of large-scale exome sequencing to elucidate the genetic architecture of common disorders where both common and rare variation contribute to risk
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