596 research outputs found

    Is bilateral aid responding to good governance in Africa?

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    This paper investigates whether aid flows from traditional donor countries to African countries have responded to improved governance in African countries, whether aid has been used by donors to improve the quality of governance in the last two decades; it also investigates alternative sources of development financing, especially from the Global South, as well as researchesnewmodalities of aid delivery. Using the insights provided by several alternative approaches, the paper finds that at the aggregate level, aid flows to African countries respond positively to improved governance. However, there are wide variations in country experiences while aid flows to some countries respond positively to improved governance, aid flows to other countries are not in any way related to changes in governance. The paper finds that while all donor countries purport to increase aid flows in response to improved governance, donors generally tend to follow their national interests and focus on aspects of governance that are consistent with their foreign policy interests but not necessarily the governance as more broadly conceived. Although some donors respond positively to improved governance and may withhold aid for egregious violations of human rights, most donors give aid to further their strategic interests even in the face of poor governance records of recipient countries. While some donors provide aid to support activities that improve governance, donors have generally not used increased resources to support activities to improve governance. Africa countrieson the other hand have learnt to take advantage of the ambivalence of donors towards governance reforms by promising to reform governance in exchange for aid without following through with the promises. The paper also finds that there are several sources of alternative development financing, available especially from the Global South. While these sources provide relatively small amounts of financing, they are rapidly increasing in importance and it behooves African countries to seek these sources not only as additional sources of development financing but also as a way of diversifying funding sources. In addition, the delivery mode of development financing from these sources is different from those of the traditional sources and may be more suitable to African needs. Finally, the paper finds that a new mode of aid delivery cash on delivery may not be easily implantable in African countries. Key words: donors, bilateral aid, governance, cash-on-delivery, Afric

    Transmission of murine scrapie to P101L transgenic mice

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    Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177Item is not available in this repository.The PrP protein is central to the transmissible spongiform encephalopathies (TSEs), and the amino acid sequence of this protein in the host can influence both incubation time of disease and targeting of disease pathology. The N terminus of murine PrP has been proposed to be important in the replication of TSE agents, as mutations or deletions in that region can alter the efficiency of agent replication. To address this hypothesis and to investigate the mechanisms by which host PrP sequence controls the outcome of disease, we have assessed the influence of a single amino acid alteration in the N-terminal region of murine PrP (P101L) on the transmission of TSE agents between mice. Mice homozygous for the mutation (101LL) were inoculated with TSE strains 139A and 79A derived from mice carrying a Prnpa allele, and 79V and 301V derived from mice carrying a Prnpb allele. Incubation times in 101LL mice were extended with all four strains of agent when compared with those in the corresponding mouse genotype from which the infectivity was derived. However, the degree to which the incubation period was increased showed considerable variation between each strain of agent. Moreover, the presence of this single amino acid alteration resulted in a 70 day reduction in incubation time of the 301V strain in Prnpa mice. The effect of the 101L mutation on murine scrapie incubation time appears therefore to be strain specific.https://doi.org/10.1099/vir.0.19147-084pubpub1

    Clinical and cost effectiveness of a multi-professional medication reviews in care homes (CAREMED)

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    Objectives With 70% of care home residents experiencing a medication error every day in the UK, better multi‐professional working between medical practitioners, pharmacists and care homes was recommended. The aim of this study was to determine the effectiveness (falls reduction) and cost‐effectiveness, of a multi‐professional medication review (MPMR) service in care homes for older people. Method A total of care homes in the East of England were cluster randomised to ‘usual care’ or two multi‐professional (General practitioner, clinical pharmacist and care homes staff) medication reviews during the 12‐month trial period. Target recruitment was 900 residents with 10% assumed loss to follow‐up. Co‐primary outcome measures were number of falls and potentially inappropriate prescribing assessed by the Screening Tool of Older Persons Prescriptions. Key findings A total of 826 care home residents were recruited with 324 lost to follow‐up for at least one primary outcome measure. The mean number of falls per resident per annum was 3.3 for intervention and 3.0 for control (P = 0.947). Each resident was found to be prescribed 0.69 (intervention) and 0.85 (control) potentially inappropriate medicines after 12 months (P = 0.046). No significant difference identified in emergency hospital admissions or deaths. Estimated unadjusted incremental mean cost per resident was £374.26 higher in the intervention group. Conclusions In line with other medication review based interventions in care homes, two MPMRs improved medication appropriateness but failed to demonstrate improvements in clinical outcomes. From a health system perspective costs where estimated to increase overall and therefore a different model of medicines management is required

    Heterogeneities in leishmania infantum infection : using skin parasite burdens to identify highly infectious dogs

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    Background: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs

    Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom

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    Array based comparative genomic hybridisation (aCGH) is a powerful technique for detecting clinically relevant genome imbalance and can offer 40 to > 1000 times the resolution of karyotyping. Indeed, idiopathic learning disability (ILD) studies suggest that a genome-wide aCGH approach makes 10–15% more diagnoses involving genome imbalance than karyotyping. Despite this, aCGH has yet to be implemented as a routine NHS service. One significant obstacle is the perception that the technology is prohibitively expensive for most standard NHS clinical cytogenetics laboratories. To address this, we investigated the cost-effectiveness of aCGH versus standard cytogenetic analysis for diagnosing idiopathic learning disability (ILD) in the NHS. Cost data from four participating genetics centres were collected and analysed. In a single test comparison, the average cost of aCGH was £442 and the average cost of karyotyping was £117 with array costs contributing most to the cost difference. This difference was not a key barrier when the context of follow up diagnostic tests was considered. Indeed, in a hypothetical cohort of 100 ILD children, aCGH was found to cost less per diagnosis (£3,118) than a karyotyping and multi-telomere FISH approach (£4,957). We conclude that testing for genomic imbalances in ILD using microarray technology is likely to be cost-effective because long-term savings can be made regardless of a positive (diagnosis) or negative result. Earlier diagnoses save costs of additional diagnostic tests. Negative results are cost-effective in minimising follow-up test choice. The use of aCGH in routine clinical practice warrants serious consideration by healthcare providers

    Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental

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    CD8(+) T lymphocytes recognize infected cells that display virus-derived antigenic peptides complexed with major histocompatibility complex class I molecules. Peptides are mainly byproducts of cellular protein turnover by cytosolic proteasomes. Cytosolic tripeptidyl-peptidase II (TPPII) also participates in protein degradation. Several peptidic epitopes unexpectedly do not require proteasomes, but it is unclear which proteases generate them. We studied antigen processing of influenza virus nucleoprotein epitope NP(147-155), an archetype epitope that is even destroyed by a proteasome-mediated mechanism. TPPII, with the assistance of endoplasmic reticulum trimming metallo-aminopeptidases, probably ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing), was crucial for nucleoprotein epitope generation both in the presence of functional proteasomes and when blocked by lactacystin, as shown with specific chemical inhibitors and gene silencing. Different protein contexts and subcellular targeting all allowed epitope processing by TPPII as well as trimming. The results show the plasticity of the cell's assortment of proteases for providing ligands for recognition by antiviral CD8(+) T cells. Our observations identify for the first time a set of proteases competent for antigen processing of an epitope that is susceptible to destruction by proteasomes.This work was supported in part by grants from Spanish Ministerio de Educación y Ciencia and from Instituto de Salud Carlos III (to M. D. V.), by a grant from Spanish Ministerio de Educación y Ciencia (to L. C. A.), by an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and by a grant from Comunidad de Madrid (to M. D. V. and L. C. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.S

    Understanding implementability in clinical trials : a pragmatic review and concept map

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    Background The translation of evidence from clinical trials into practice is complex. One approach to facilitating this translation is to consider the 'implementability' of trials as they are designed and conducted. Implementability of trials refers to characteristics of the design, execution and reporting of a late-phase clinical trial that can influence the capacity for the evidence generated by that trial to be implemented. On behalf of the Australian Clinical Trials Alliance (ACTA), the national peak body representing networks of clinician researchers conducting investigator-initiated clinical trials, we conducted a pragmatic literature review to develop a concept map of implementability. Methods Documents were included in the review if they related to the design, conduct and reporting of late-phase clinical trials; described factors that increased or decreased the capacity of trials to be implemented; and were published after 2009 in English. Eligible documents included systematic reviews, guidance documents, tools or primary studies (if other designs were not available). With an expert reference group, we developed a preliminary concept map and conducted a snowballing search based on known relevant papers and websites of key organisations in May 2019. Results Sixty-five resources were included. A final map of 38 concepts was developed covering the domains of validity, relevance and usability across the design, conduct and reporting of a trial. The concepts drew on literature relating to implementation science, consumer engagement, pragmatic trials, reporting, research waste and other fields. No single resource addressed more than ten of the 38 concepts in the map. Conclusions The concept map provides trialists with a tool to think through a range of areas in which practical action could enhance the implementability of their trials. Future work could validate the strength of the associations between the concepts identified and implementability of trials and investigate the effectiveness of steps to address each concept. ACTA will use this concept map to develop guidance for trialists in Australia

    Biochemical comparison of two Hypostomus populations (Siluriformes, Loricariidae) from the Atlântico Stream of the upper Paraná River basin, Brazil

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    Two syntopic morphotypes of the genus Hypostomus - H. nigromaculatus and H. cf. nigromaculatus (Atlântico Stream, Paraná State) - were compared through the allozyme electrophoresis technique. Twelve enzymatic systems (AAT, ADH, EST, GCDH, G3PDH, GPI, IDH, LDH, MDH, ME, PGM and SOD) were analyzed, attributing the score of 20 loci, with a total of 30 alleles. Six loci were diagnostic (Aat-2, Gcdh-1, Gpi-A, Idh-1, Ldh-A and Mdh-A), indicating the presence of interjacent reproductive isolation. The occurrence of few polymorphic loci acknowledge two morphotypes, with heterozygosity values He = 0.0291 for H. nigromaculatus and He = 0.0346 for H. cf. nigromaculatus. FIS statistics demonstrated fixation of the alleles in the two morphotypes. Genetic identity (I) and distance (D) of Nei (1978) values were I = 0.6515 and D = 0.4285. The data indicate that these two morphotypes from the Atlântico Stream belong to different species

    LSST: from Science Drivers to Reference Design and Anticipated Data Products

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    (Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2^2 field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5σ\sigma point-source depth in a single visit in rr will be 24.5\sim 24.5 (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg2^2 with δ<+34.5\delta<+34.5^\circ, and will be imaged multiple times in six bands, ugrizyugrizy, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg2^2 region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to r27.5r\sim27.5. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

    Allozyme differentiation of two populations of the genus Neoplecostomus Eigenmann & Eigenmann, 1888 (Teleostei, Loricariidae) from the upper Paraná River basin, Brazil

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    Allozyme electrophoresis was used to examine 12 enzymatic systems in two populations of the genus Neoplecostomus from the Paraná River basin. Samples of Neoplecostomus sp. 1 were collected in Paraitinguinha stream of the Tietê River basin, in the municipality of Salesópolis, São Paulo State, and those of Neoplecostomus sp. 2 from São Domingos stream of the Rio Grande River basin, in the municipality of Muzambinho, Minas Gerais State. The genetic variability of the two populations was estimated by Nei’s expected heterozygosity and was considered lower than average for populations of freshwater fish. The proportion of polymorphic loci was low (only 5.26% for the locus Idh). The low frequency of heterozygosity for both populations revealed a high fixation of alleles for each locus. Homozygote excess was observed in both populations. The values of Nei’s genetic identity and the presence of loci with different allele frequencies in both populations may imply that the two populations belong to different species. The genetic variability between populations was compared to other data for loricariids
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