821 research outputs found

    Drugs for 'neglected diseases': a bitter pill.

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    How Planting Density Affects Number and Yield of Potato Minitubers in a Commercial Glasshouse Production System

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    Commercial potato minituber production systems aim at high tuber numbers per plant. This study investigated by which mechanisms planting density (25.0, 62.5 and 145.8 plants/m2) of in vitro derived plantlets affected minituber yield and minituber number per plantlet. Lowering planting density resulted in a slower increase in soil cover by the leaves and reduced the accumulated intercepted radiation (AIR). It initially also reduced light use efficiency (LUE) and harvest index, and thus tuber weights per m2. At the commercial harvest 10 weeks after planting (WAP), LUE tended to be higher at lower densities. This compensated for the lower AIR and led to only slightly lower tuber yields. Lowering planting density increased tuber numbers per (planted) plantlet in all grades. It improved plantlet survival and increased stem numbers per plant. However, fewer stolons were produced per stem, whereas stolon numbers per plant were not affected. At lower densities, more tubers were initiated per stolon and the balance between initiation and later resorption of tubers was more favourable. Early interplant competition was thought to reduce the number of tubers initiated at higher densities, whereas later-occurring interplant competition resulted in a large fraction of the initiated tubers being resorbed at intermediate planting densities. At low planting densities, the high number of tubers initiated was also retained. Shortening of the production period could be considered at higher planting densities, because tuber number in the commercial grade > 9 mm did not increase any more after 6 WA

    A randomized comparison of branded sodium stibogluconate and generic sodium stibogluconate for the treatment of visceral leishmaniasis under field conditions in Sudan.

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    OBJECTIVE: To compare the outcome of treatment of Sudanese kala-azar patients treated under field conditions with either branded sodium stibogluconate (SSG) (Pentostam GlaxoWellcome) or generic SSG (Albert David Ltd, Calcutta, supplied by International Dispensary Association, Amsterdam). METHOD: Randomised comparison. 271 patients were treated with Pentostam and 245 with generic SSG. RESULTS: No statistically significant differences in cure rate or mortality were detected between Pentostam and generic SSG. No differences in side-effects between the two drugs were noted. The initial cure rate at the time of discharge was 93.7 and 97.6%, respectively; the death rate during treatment 5.9 and 2.4%. Six months follow up was achieved in 88.5% of the discharged patients. Two patients had died in the Pentostam group and two had died in the generic SSG group, giving a final death rate of 7.5 and 3.7%. The number of relapses in the Pentostam and generic SSG groups were 3 and 1, respectively. The final cure rates, calculated at 6 months after discharge, were 91.3% and 95.9%. CONCLUSION: No difference was observed in the performance of generic SSG compared to Pentostam for the treatment of visceral leishmaniasis in Sudan. Generic SSG can be routinely and safely used for the treatment of kala-azar. Generic SSG costs only 1/14 of the price of Pentostam. The use of generic SSG may make treatment of kala-azar affordable for national governments in Africa

    Dynamic partitioning of nanoparticulate metal species between gel layers and aqueous media

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    This thesis deals with several aspects of the use of Diffusive Gradient in Thin film (DGT) and Diffusive Equilibriation in Thin film (DET) in dynamic metal speciation analysis. It has a clear focus on the properties of the diffusive gel layer, and their possible impact on metal speciation measurements in samples containing nanoparticulate and colloidal complexing agents. The introductory chapter already announced the paramount feature of the DGT technique, which is the well-defined control over the diffusive layer thickness. DGT realizes this via the introduction of a hydrogel layer in which diffusion is the sole mode of transport for ions and complexes that are able to enter the gel phase. The rate of diffusive transport across the gel layer is then governed by the species mobility and the layer thickness, with the latter parameter being under full control of the analyst. In order to maintain a limiting steady-state flux across the gel layer, it is backed by a strong cation exchange layer that acts as a perfect sink for metal ions. The most common set-up uses a Chelex-resin. Current research is exploring the use of dedicated binding agents for more specific uses in a variety of environmental systems, e.g. Teasdale et al. (1-4). Nowadays, DGT is being employed for systems that are increasingly complex, and sometimes largely uncharacterized. For example, numerous experiments have been performed on the use of DGT in soils (5, 6), laser ablation for element detection at high spatial resolution (7, 8) and array-type setups for simultaneous deployment of larger numbers of DGT sensor units. Although this creative branching opens up a lot of opportunities, it also introduces a host of potential complications that require dedicated solutions. Nevertheless, more detailed knowledge is required to address the pitfalls that are already present in the most straightforward application of DGT in aquatic systems. Here we do this to a significant extent by combining DGT with DET measurements on the same sample system, using exactly the same gel in each case, to fully utilize the complementary nature of the two techniques. Chapter 2 investigates the pore size of two common types of DGT diffusive gels. They are usually known as “open pore” (APA2) and “restricted” (RG) gel. Both gels have been shown to be fully permeable to metal ions and small complexes. However, it has been generally assumed that colloidal particles with radii from tens to hundreds of nm are excluded from the gel. This chapter describes DGT and DET measurements in model dispersions of differently sized synthetic particles. These particles bind Pb(II) from solution, in essence providing us with probes using Pb(II) as a marker which is easily detectable by ICP-MS. The particles involved are monodisperse, carboxylated latex nanospheres with radii 40.5 nm and 129 nm. Extensive information on their diffusion coefficients and ion binding affinities for various metals, under a range of pH and ionic strength conditions, is available. Apart from them being well characterized and excellently monodisperse, the main interest in using these particular particles as model colloidal ligands is their size and their relatively large metal binding site density. DET results show a very clear difference compared to those for a system where no permeation would take place. Time-resolved investigation of the DET process clearly shows the slow process of diffusion of large particles into the gel, and the amount measured at equilibrium is the sum of the concentrations of the free and particle-bound metal in the gel. DGT, on the other hand, measures the mobility-weighted sum of these concentrations. As a consequence, DGT speciation analysis of samples possibly containing colloidal species call for parallel DET experiments. This combination of techniques makes it possible to determine the concentration of both the free and the particle-bound metal, provided the ratio between the mobilities of the two types of species is known. In Chapter 3, attention is shifted from pore size features to the charge properties of the diffusive gel. Often the assumption is made that the gel matrix is effectively uncharged and chemically inert with respect to the species of interest. Prior to the work performed for this thesis however, research on the same gel (DGT) by Yezek et al. (9, 10) showed significant non-ideal behavior at relatively low ionic strength, suggesting a finite structural electric charge within the gel matrix. Such structural charge within the gel layer gives rise to species concentrations in the gel phase that are different from those in the sample. The steady-state diffusion of ions through the gel is also influenced by the structural charge, but the net effect will depend on the details of the speciation. Perturbations of the concentrations and fluxes of ions in the gel phase as compared to the sample solution are particularly troublesome because quantitative interpretations for submillimolar ionic strength solutions are common in freshwater research. We highlight how to calculate the correction factor needed for the particular ionic strength of the sample and the characteristics of the gel used. However, Donnan partitioning affects not only the total metal concentration in the gel phase, but also the relative concentrations of all charged species. Hence, the entire metal speciation within the gel phase depends on the magnitude of the Donnan potential. Consequently, the relationship between the amount of metal measured by DGT and the corresponding metal species distribution in the bulk sample solution may adopt a rather involved nature. Again, due to the inherent differences between DET and DGT, complementary DET deployment appears helpful, if not indispensable. Chapter 4 starts our investigation into the effects of the natural ligands humic acid (HA) and fulvic acid (FA) on DGT and DET metal speciation measurements. Knowledge on the impact of such complexing agents on dynamic metal ion speciation is fundamental to understanding many processes in aquatic media. Humic and fulvic acids are highly complex and diverse, and are found in a large variety of natural settings, from soils and sediments to marine waters and freshwaters. The environmental abundance and ligand traits of HA and FA imply that they are also of major importance for the bioavailability of heavy metals. Previous DGT research has focused on the effects of HA and FA in the sample solutions while ignoring the ultimate sample/gel partitioning fate of the HA and FA particles themselves. Here we analyze solutions of Suwannee River Fulvic Acid standard (SRFA) and a specific Forest Soil Humic Acid (FSHA) and show with DET that these natural complexing agents do enter the gel layer. The humic acid even appears to accumulate in the gel, with typical enrichment factors up to several tens. The accumulation is especially strong at relatively low ionic strength, implying a very substantial accumulation under freshwater conditions, while media with an ionic strength similar to that of marine conditions showed no accumulation at all. Other research on humic acids has shown that, due to the heterogeneous distribution of the charged groups within the humic structure, these substances are able to form so-called “pseudomicelles”. At lower ionic strength, the pseudomicelle formation is counteracted by increased repulsion between the charged groups, which enhances the availability of the more hydrophobic center of the FSHA entity to binding by the polyacrylamide gel backbone instead. Time-dependent DET measurements confirm the migration of humic acid into the gel phase. The rate of this process indicates that the steady-state achievement time for DGT, which is already large due to the low mobilities, will be substantially further enlarged due to the strong accumulation in the gel. Further research on the accumulation properties of different types of humic acids, for various ionic strengths, from freshwaters to marine levels, will be mandatory. The results herein have significant consequences for the interpretation of DGT-data on metal fluxes from aquatic media containing humics and fulvics. Chapter 5 extends the research to the accumulation of humic and fulvic acids in the presence of metal ions, specifically cadmium(II), and the consequences for interpretation of speciation. The changes in the partitioning of HA and FA, as well as the partitioning of cadmium itself, are measured. At millimolar ionic strength level, DET data show significant accumulation of Cd(II) in the gel phase, on top of some Donnan enrichment. It is shown that the accumulation of HA is significantly influenced by the presence of the cadmium ions, and vice versa. The accumulation of both FSHA and metals is again strongest at relatively low ionic strength. It seems that the presence of metal ions significantly influences the formation of HA pseudomicelles, which in turn has a significant effect on the transport of the metal species themselves through the gel layer. Future research may include an extension of this study to different combinations of humic acids and heavy metals, and their accumulation and gel partition properties for various ionic strengths. Chapter 6 discusses the impact of the accumulation of humic acid in the gel layer on the properties of the DGT metal flux for various experimental conditions. The inherent complications due to the accumulation of the different species are exacerbated by the simultaneous Donnan effects for all charged species. For samples with insufficiently defined natural ligands, the interpretation of DGT fluxes generally requires independent information on physicochemical parameters such as affinities between complexing ligands and the gel backbone. Accordingly, the translation of DGT fluxes to metal speciation dynamics in freshwaters containing humic substances may be rather involved and certainly requires careful consideration of factors such as lability, interaction with the gel backbone and Donnan effects. Therefore it is strongly recommended to (i) perform measurements including variation of deployment time for accurate determination of the steady-state achievement time, and (ii) deliberately combine DGT flux measurements with DET equilibrium data on the gel/sample partitioning of both metals and humics. References (1) Li, W.; Zhao, H.; Teasdale, P.R.; John, R.; Zhang, S. Synthesis and characterisation of a polyacrylamide-polyacrylic acid copolymer hydrogel for environmental analysis of Cu and Cd. React. Funct. Polym. 2002, 52, 31-41. (2) Li, W.; Zhao, H.; Teasdale, P.R.; John, R.; Zhang, S. Application of a cellulose phosphate ion exchange membrane as a binding phase in the diffusive gradients in thin films technique for measurement of trace metals. Anal. Chim. Acta 2002, 464, 331-339. (3) Li, W.J.; Teasdale, P.R.; Zhang, S.Q.; John, R.; Zhao, H.J. Application of a poly(4-styrenesulfonate) liquid binding layer for measurement of CU2+ and Cd2+ with the diffusive gradients in thin-films technique. Anal. Chem. 2003, 75, 2578-2583. (4) Li, W.J.; Zhao, H.J.; Teasdale, P.R.; John, R.; Wang, F.Y. Metal speciation measurement by diffusive gradients in thin films technique with different binding phases. Anal. Chim. Acta 2005, 533, 193-202. (5) Zhang, H.; Davison, W.; Knight, B.; McGrath, S. In situ measurements of solution concentrations and fluxes of trace metals in soils using DGT. Environ. Sci. Technol. 1998, 32, 704-710. (6) Sochaczewski, L.; Tych, W.; Davison, W.; Zhang, H. 2D DGT induced fluxes in sediments and soils (2D DIFS). Environ. Modell. Softw. 2007, 22, 14-23. (7) Warnken, K.W.; Zhang, H.; Davison, W. Analysis of polyacrylamide gels for trace metals using diffusive gradients in thin films and laser ablation inductively coupled plasma mass spectrometry. Anal. Chem. 2004, 76, 6077-6084. (8) Warnken, K.W.; Zhang, H.; Davison, W. Accuracy of the diffusive gradients in thin-films technique: Diffusive boundary layer and effective sampling area considerations. Anal. Chem. 2006, 78, 3780-3787. (9) Yezek, L.P.; van Leeuwen, H.P. An electrokinetic characterization of low charge density cross-linked polyacrylamide gels. J. Colloid Interface Sci. 2004, 278, 243-250. (10) Yezek, L. P.; van Leeuwen, H. P. Donnan effects in the steady-state diffusion of metal ions through charged thin films. Langmuir 2005, 21, 10342-10347. <br/

    Routine outcome monitoring as a compass in forensic clinical treatment

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    Onderzoek naar het Instrument voor de Forensische Behandel Evaluatie (IFBE) in een tbs-populatie geeft de eerste aanwijzingen dat het instrument als kompas in de forensisch psychiatrische behandeling gebruikt kan worden. Het meten van behandeluitkomsten is al meerdere jaren de standaard binnen de geestelijke gezondheidszorg (GGZ). De tbs-behandeling heeft als doel om de kans op een nieuw delict te verminderen en een patiënt te laten resocialiseren in de maatschappij. Vanuit dit oogpunt is het belangrijk dat behandeling afgestemd wordt op het risico, de factoren die dit risico vergroten of juist verkleinen en de mogelijkheden en sterktes van de patiënt zelf. De huidige tbs-behandeling duurt lang en het is van belang dat de behandeling periodiek geëvalueerd wordt. Het IFBE is speciaal ontwikkeld om de behandeling vanuit deze oogpunten te evalueren. In het proefschrift 'Routine Outcome Monitoring as a Compass in Forensic Clinical Treatment' is door Frida van der Veeken onderzocht of het IFBE geschikt is om richting te geven aan de behandeling. In 2011 is in FPC de Kijvelanden en FPC 2landen gestart met de reguliere afname van het IFBE samen met aanvullende instrumenten voor de verschillende groepen mannelijke patiënten met een tbs-maatregel. Vervolgens is onderzocht of er onderscheidbare 'profielen' zijn te identificeren op basis van het type delict, de psychiatrische diagnostiek en de aanwezige risicofactoren. Aansluitend is gekeken of het IFBE goede psychometrische kwaliteiten heeft om te gebruiken in de forensisch psychiatrische zorg. Hiernaast is onderzocht of de vragen van het IFBE en de drie factoren van het IFBE (beschermend gedrag, probleem gedrag en resocialisatie vaardigheden), voorspellend zijn voor toekomstige agressie en voor middelengebruik. Ook is gekeken of de IFBE scores gerelateerd zijn aan toekomstig verlof. Als laatste is onderzocht of het IFBE verandering in kaart kan brengen op de drie factoren. De resultaten in het proefschrift laten zien dat het IFBE voldoende psychometrische kwaliteiten heeft en dat de overeenstemming tussen behandelaren en de test-hertest betrouwbaarheid voor de meeste items voldoende is. Het voordeel van het IFBE is dat meerdere disciplines het instrument tegelijkertijd kunnen scoren wat leidt tot één samengestelde score. De indeling van de drie factoren wordt in het onderzoek slechts deels ondersteund en verdient verder onderzoek in een grotere populatie. Analyses onderscheiden vier profielen welke een beschrijving geven van de tbs-populatie. Omdat deze echter niet aan alle voorwaarden voldoen, is het niet mogelijk geweest de specifieke behandelvoortgang voor deze profielen te onderzoeken. Het onderzoek naar de behandelvoortgang toont geen voortgang op groepsniveau. Dit heeft mogelijk te maken met de diversiteit van de populatie, de gekozen meetmomenten en het feit dat niet de gehele behandelduur is meegenomen. Patiënten die meer 'problematisch' scoren op een van de factoren laten echter wel voortgang zien op dezelfde factor. Patiënten met een minder 'problematische' score laten echter een trend van achteruitgang zien.Dit proefschrift laat zien dat het IFBE gebruikt kan worden in de forensisch psychiatrische behandeling als ROM-instrument. Toekomstig onderzoek naar het gebruik van feedback en de relatie van de behandelvoortgang met recidive kan verder bijdragen aan het gebruik van het IFBE en de forensische ROM als kompas in de behandeling. Het IFBE zou dan kunnen bijdragen aan het tijdig signaleren van patiënten die geen voortgang of zelfs achteruitgang vertonen. Op die manier zou het IFBE een korter traject, tijdige wijziging van het behandelplan of geïnformeerde besluitvorming kunnen stimuleren. Tenslotte is het niet onbelangrijk te vermelden dat het IFBE gebruiksvriendelijk is en weinig tijd in beslag neemt om te scoren. Het is van belang dat ROM niet als een last en verplichting wordt gezien, maar gebruikt wordt door behandelaren ten bate van de behandeling

    Faraday Current Sensing

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