451 research outputs found

    Effect of hydraulic parameters on sediment transport capacity in overland flow over erodible beds

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    Sediment transport is an important component of the soil erosion process, which depends on several hydraulic parameters like unit discharge, mean flow velocity, and slope gradient. In most of the previous studies, the impact of these hydraulic parameters on transport capacity was studied for non-erodible bed conditions. Hence, this study aimed to examine the influence of unit discharge, mean flow velocity and slope gradient on sediment transport capacity for erodible beds and also to investigate the relationship between transport capacity and composite force predictors, i.e. shear stress, stream power, unit stream power and effective stream power. In order to accomplish the objectives, experiments were carried out in a 3.0 m long and 0.5 m wide flume using four well sorted sands (0.230, 0.536, 0.719, 1.022 mm). Unit discharges ranging from 0.07 to 2.07 × 10<sup>−3</sup> m<sup>2</sup> s<sup>−1</sup> were simulated inside the flume at four slopes (5.2, 8.7, 13.2 and 17.6%) to analyze their impact on sediment transport rate. The sediment transport rate measured at the bottom end of the flume by taking water and sediment samples was considered equal to sediment transport capacity, because the selected flume length of 3.0 m was found sufficient to reach the transport capacity. The experimental result reveals that the slope gradient has a stronger impact on transport capacity than unit discharge and mean flow velocity due to the fact that the tangential component of gravity force increases with slope gradient. Our results show that unit stream power is an optimal composite force predictor for estimating transport capacity. Stream power and effective stream power can also be successfully related to the transport capacity, however the relations are strongly dependent on grain size. Shear stress showed poor performance, because part of shear stress is dissipated by bed irregularities, bed form evolution and sediment detachment. An empirical transport capacity equation was derived, which illustrates that transport capacity can be predicted from median grain size, total discharge and slope gradient

    Afgewezen en uit Nederland vertrokken? Een onderzoek naar de achtergronden van variatie in zelfstandige terugkeer onder uitgeprocedeerde asielzoekers

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    __Abstract__ In de periode 2008 tot en met maart 2010 heeft het Wetenschappelijk Onderzoek- en Documentatiecentrum (WODC) voor het eerst uitgebreid onderzoek gedaan naar de vraag hoe verklaard kan worden dat sommige uitgeprocedeerde asielmigranten met hulp van de Nederlandse overheid besluiten om zelfstandig terug te keren, ter-wijl anderen er de voorkeur aan geven om illegaal in Nederland te blijven of even-tueel door te migreren naar een ander land.1 De Directie Migratiebeleid (DMB) heeft het WODC verzocht een vervolgstudie te verrichten naar zelfstandige terugkeer. Dit rapport vormt de neerslag van deze vervolgstudie. Er is in de volgende opzichten voortgebouwd op het eerdere terugkeeronderzoek. Ten eerste is er in dit onderzoek gekeken naar feitelijk terugkeergedrag (geregis-treerde terugkeer via IOM) in plaats van naar terugkeerintenties en -attitudes, die in de eerdere studie centraal stonden. Ten tweede wordt terugkeer nu in verband gebracht met onafhankelijke gegevens over maatschappelijke omstandigheden in herkomstlanden. Ten derde wordt ditmaal uitgebreider gekeken naar de mogelijke invloed van terugkeerprogramma’s op zelfstandige terugkeer. Ten vierde is er nu ook onderzoek gedaan naar de vraag of de kans op terugkeer afhangt van demo-grafische kenmerken van afgewezen asielzoekers (zoals geslacht, leeftijd en gezins-samenstelling) en de tijd die de IND nodig heeft om een asielaanvraag te beoorde-len (procedureduur in eerste aanleg). De centrale vraag van het onderzoek luidt: In hoeverre stimuleren beleidsinstrumenten op het gebied van terugkeer de zelf-standige terugkeer via IOM wanneer wordt gecontroleerd voor relevante individuele kenmerken en sociaaleconomische en politieke omstandigheden in het land van herkomst

    Growth factors of stem cell niche extend the life-span of precision-cut intestinal slices in culture:A proof-of-concept study

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    Precision-cut intestinal slices (PCIS) is an ex vivo culture technique that found its applications in toxicology, drug transport and drug metabolism testing, as well as in fibrosis research. The main limiting factor of PCIS as experimental model is the relatively short viability of tissue slices. Here, we describe a strategy for extending the life-span of PCIS during culture using medium that is routinely used for growing intestinal organoids. Mouse and rat PCIS cultured in standard medium progressively showed low ATP/protein content and severe tissue degradation, indicating loss of tissue viability. In turn, organoid medium, containing epithelial growth factor (EGF), Noggin and R-spondin, maintained significantly higher ATP/protein levels and better preserved intestinal architecture of mouse PCIS at 96 h. In contrast, organoid medium that additionally contained Wnt, had a clear positive effect on the ATP content of rat PCIS during 24 h of culture, but not on slice histomorphology. Our proof-of-concept study provides early evidence that employing organoid medium for PCIS culture improved tissue viability during extended incubation. Enabling lasting PCIS cultures will greatly widen their range of applications in predicting long-term intestinal toxicity of xenobiotics and elucidating their mechanism of action, among others

    Interleukin-1 beta Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-beta 1

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    One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ). TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, -2, -9 and -14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti-fibrotic treatment regimes

    Triage conducted by lay-staff and emergency training reduces paediatric mortality in the emergency department of a rural hospital in Northern Mozambique

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    Introduction The majority of emergency paediatric death in African countries occur within the first 24 h of admission. A coloured triage system is widely implemented in high-income countries and the emergency triage and assessment treatment (ETAT) is recommended by the World Health Organization, but not put into practice in Mozambique. We implemented a three-colour triage system in a rural district hospital with lay-staff workers conducting the first triage. Methods A retrospective, before and after, mortality analysis was performed using routine patient files from the district hospital between 2014 and 2017. The triage system was implemented in August 2016. Inclusion criteria were children under 15 years of age that entered the emergency centre. Primary outcome was child mortality rate. Secondary outcomes included the percentage agreement between the clinical and non-clinical staff and the duration from triage to first treatment. We used a negative binomial model in STATA 15 to compare mortality rates, and Kappa statistics to estimate the agreement between clinical and non-clinical staff. Results 4176 admissions were included. The mortality rate ratio (MMR) was 45% lower after the start of the intervention (2016; MRR = 0.55; 0.38, 0.81; p = 0.002), compared to before. To estimate the agreement between non-clinical and clinical staff, 548 (of the 671) patient files were included. The agreement was estimated at 88.7% (Kappa = 0.644; p < 0.001). The median waiting time decreased with urgency of the triage: 2 h33 for ‘green’/least serious (IQR 1 h58-3 h30), 21 min for yellow/serious (IQR 0 h10-0 h58) and nine minutes for ‘red’/urgent (IQR 2–40 min). Conclusion In a rural setting with nurse-led clinical care and non-clinician staff working at the triage reception, implementation of a three-coloured triage system was feasible. Triage and ETAT training was associated with a decrease of 45% of paediatric deaths. The impact on mortality, low cost, and ease of the implementation supports scaling this intervention in similar settings

    Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices

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    Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and triggered the onset of fibrogenesis in all PCTS in organ-specific manner. TGFβ signalling was activated during 48 h culture in all PCTS. However, the degree of its involvement varied: both canonical and non-canonical TGFβ pathways were activated in liver and kidney slices, while only canonical, Smad-dependent, cascade was involved in intestinal slices. The treatment with galunisertib blocked the TGFβRI/SMAD2 signalling in all PCTS, but attenuated culture-induced dysregulation of ECM homeostasis and mitigated the onset of fibrogenesis with organ-specificity. In conclusion, regardless the many common features in pathophysiology of organ fibrosis, PCTS displayed diversity in culture-induced responses and in response to the treatment with TGFβRI kinase inhibitor galunisertib, even though it targets a core fibrosis pathway. A clear understanding of the common and organ-specific features of fibrosis is the basis for developing novel antifibrotic therapies
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