1,721,206 research outputs found
Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa.
Get PDFThe efficacy of anti-malarial drugs is assessed over a period of 28-63 days (depending on the drugs' residence time) following initiation of treatment in order to capture late failures. However, prolonged follow-up increases the likelihood of new infections depending on transmission intensity. Therefore, molecular genotyping of highly polymorphic regions of Plasmodium falciparum msp1, msp2 and glurp loci is usually carried out to distinguish recrudescence (true failures) from new infections. This tool has now been adopted as an integral part of anti-malarial efficacy studies and clinical trials. However, there are concerns over its utility and reliability because conclusions drawn from molecular typing depend on the genetic profile of the respective parasite populations, but this profile is not systematically documented in most endemic areas. This study presents the genetic diversity of P. falciparum msp1, msp2 and glurp markers in selected sub-Saharan Africa countries with varying levels of endemicity namely Malawi, Tanzania, Uganda, Burkina Faso and São Tomé.A total 780 baseline (Day 0) blood samples from children less than seven years, recruited in a randomized controlled clinical trials done between 1996 and 2000 were genotyped. DNA was extracted; allelic frequency and diversity were investigated by PCR followed by capillary electrophoresis for msp2 and fragment sizing by a digitalized gel imager for msp1 and glurp. Plasmodium falciparum msp1, msp2 and glurp markers were highly polymorphic with low allele frequencies. A total of 17 msp1 genotypes [eight MAD20-, one RO33- and eight K1-types]; 116 msp2 genotypes [83 3D7 and 33 FC27- types] and 14 glurp genotypes were recorded. All five sites recorded very high expected heterozygosity (HE) values (0.68 - 0.99). HE was highest in msp2 locus (HE=0.99), and lowest for msp1 (HE=0.68) (P<0.0001). The genetic diversity and allelic frequency recorded were independent of transmission intensity (P=0.84, P=0.25 respectively. A few genotypes had particularly high frequencies; however the most abundant showed only a 4% probability that a new infection would share the same genotype as the baseline infection. This is unlikely to confound the distinction of recrudescence from new infection, particularly if more than one marker is used for genotyping. Hence, this study supports the use of msp1, msp2 and glurp in malaria clinical trials in sub-Saharan Africa to discriminate new from recrudescent infections
Statistical analysis of "Plasmodium falciparum" infection dynamics
Get PDFMalaria is one of the major contributors to the global burden of disease. Worldwide, there were an estimated number of 200 million malaria cases in the year 2008, with a vast majority (85%) of those being in the African Region. This has lead to an estimated number of up to one million deaths, with a similar majority (89%) happening in the African region. There are several parasite species causing malaria, but most deaths are caused by Plasmodium falciparum. Malaria remains a major challenge for scientific research: constantly the parasite evolves resistance against existing drugs, and ever new substances to cure malaria need to be found. Creating a vaccine against Plasmodium falciparum proves exceptionally difficult, because the parasite has found ways to escape the human immune response. How exactly, is poorly understood. In addition, many countries affected by the disease suffer from poverty and ineffective health infrastructure. In the 1950’s the final eradication of malaria was envisioned by the WHO: the newly discovered insecticide DDT showed very promising results in reducing the malaria burden by killing the Anopheles mosquitoes, through which malaria is transmitted, and mathematical models of malaria transmission predicted that eradication of the disease would be possible. Despite great successes in the Caribbean, parts of Asia and South-Central America, and elimination in Europe and North America during the following decades, the efforts did not succeed in tropical Africa and many parts of Asia. After that failure, malaria was a “neglected” disease for a long period. Only since recent times malaria is again high on the global health agenda. Now, the enormous progress in the life sciences during the last decades provides new tools to better understand the parasite’s natural history, and perhaps will reveal new ways of attacking it. One factor which limited the understanding of the epidemiology of the parasite was that microscopy as diagnostic tool is not able to distinguish multiple concurrent infections within one human host: people in endemic areas often harbour several infecting clones in parallel. DNA-based methods make use of genetic loci of which many different variants exist in the parasite population, e.g. merozoite surface protein 2 (msp2), to distinguish co-infecting clones. This thesis develops statistical models to analyse such data on the presence of (mostly) msp2 genotypes. In particular, data from a longitudinal study in Navrongo, Northern Ghana is used in all chapters except chapter 6, where data from Papua New Guinea is analysed. A major challenge in the analysis of this type of data is the phenomenon of imperfect detection: the parasite hides in the deep blood vessels by attaching to the capillary walls, and it can therefore not be always detected in the peripheral blood. The three parameters which are estimated by our statistical models from time-series on presence or absence of genotypes are i) the force of infection (the number of infections acquired per person and year), ii) the duration of infection for one parasite clone, and iii) the detectability (the probability of detecting a parasite, given it is present). Previous statistical methods for the analysis of longitudinal genotyping data were restricted to exponential distributions of infection duration: this means that a constant rate (per time) is assumed at which infections are cleared. The reason for this was mathematical simplicity: the age structure of the infection population within a host can be neglected because the clearance rate is constant and does not depend on the age of an infection. In other words, the same mathematical model as for radioactive decay was used. Biologically, this is a very unrealistic assumption, and to understand more about within-host dynamics of P. falciparum or immunity against it one would like to distinguish between young and old infections. This thesis develops an extension to previous statistical analysis methods and makes use of parametric survival distributions to describe infection clearance and how it depends on the age of an infection. In addition to the age of infection, the effect of host age on infection clearance is investigated: older persons have experienced more infections and are therefore more immune. Changes in infection clearance with host age can therefore be interpreted as effects of immunity. An difference between the distribution of infection durations in the Ghanaian dataset compared to artificial infections4 emerged: a large proportion of infections in the Ghanaian population are cleared quickly after inoculation. It is the first time this could be measured from field data, and the result was confirmed using a different statistical method and study design. The difference between artificial infections and the field data cannot be attributed to acquired immunity in the Ghanaian population because all age groups show a similar abundance of very short infection durations. An interaction between the multiple infections within one host in Northern Ghana appears to be the most likely explanation. The implications of this finding for our understanding of the within-host processes in falciparum malaria are discussed
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Optimization and validation of multi-coloured capillary electrophoresis for genotyping of Plasmodium falciparum merozoite surface proteins (msp1 and 2).
Get PDFBACKGROUND: Genotyping of Plasmodium falciparum based on PCR amplification of the polymorphic genes encoding the merozoite surface proteins 1 and 2 (msp1 and msp2) is well established in the field of malaria research to determine the number and types of concurrent clones in an infection. Genotyping is regarded essential in anti-malarial drug trials to define treatment outcome, by distinguishing recrudescent parasites from new infections. Because of the limitations in specificity and resolution of gel electrophoresis used for fragment analysis in most genotyping assays it became necessary to improve the methodology. An alternative technique for fragment analysis is capillary electrophoresis (CE) performed using automated DNA sequencers. Here, one of the most widely-used protocols for genotyping of P. falciparum msp1 and msp2 has been adapted to the CE technique. The protocol and optimization process as well as the potentials and limitations of the technique in molecular epidemiology studies and anti-malarial drug trials are reported. METHODS: The original genotyping assay was adapted by fluorescent labeling of the msp1 and msp2 allelic type specific primers in the nested PCR and analysis of the final PCR products in a DNA sequencer. A substantial optimization of the fluorescent assay was performed. The CE method was validated using known mixtures of laboratory lines and field samples from Ghana and Tanzania, and compared to the original PCR assay with gel electrophoresis. RESULTS: The CE-based method showed high precision and reproducibility in determining fragment size (< 1 bp). More genotypes were detected in mixtures of laboratory lines and blood samples from malaria infected children, compared to gel electrophoresis. The capacity to distinguish recrudescent parasites from new infections in an anti-malarial drug trial was similar by both methods, resulting in the same outcome classification, however with more precise determination by CE. CONCLUSION: The improved resolution and reproducibility of CE in fragment sizing allows for comparison of alleles between separate runs and determination of allele frequencies in a population. The more detailed characterization of individual msp1 and msp2 genotypes may contribute to improved assessments in anti-malarial drug trials and to a further understanding of the molecular epidemiology of these polymorphic P. falciparum antigens
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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