1,721,366 research outputs found
Data for: Oral versus Intravenous Antibiotics for Bone and Joint Infection – Randomised controlled trial
No full textThe management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. The OVIVA study investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.
We collected data on 1054 adults treated for bone of joint infection at 26 UK centres.
Participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy.
The primary end point was definitive treatment failure within 1 year after randomisation. Additional data on clinical variables (including information on line complications, episodes of C-Diff), antibiotic use, clinical reviews, severe adverse events, inpatient admissions and patient reported outcomes (EQ-5D-3L and Oxford Hip Score/ Oxford Knee Score for participants with infections in their hips/ knees). </p
Replication Data for: Twenty-Seven Years of Clinical Surveillance of Severe Malaria in Kilifi County, Kenya
No full textThis dataset contains clinical data from 18,000 children with severe malaria admitted to Kilifi County Hospital, Kenya, during a 27-year period of reducing transmission. Data collection was done through continuous surveillance of hospital admissions is ongoing in KCH since May 1989 as a partnership between the Research Programme and Kilifi County Department of Health. The dataset also includes demographic characteristics and malaria control activities such as distributions of insecticide-treated bed nets. A more detailed description of the data collection methodology is included in the related publication. </p
Replication Data for: Twenty-Seven Years of Clinical Surveillance of Severe Malaria in Kilifi County, Kenya
No full textThis dataset contains clinical data from 18,000 children with severe malaria admitted to Kilifi County Hospital, Kenya, during a 27-year period of reducing transmission. Data collection was done through continuous surveillance of hospital admissions is ongoing in KCH since May 1989 as a partnership between the Research Programme and Kilifi County Department of Health. The dataset also includes demographic characteristics and malaria control activities such as distributions of insecticide-treated bed nets. A more detailed description of the data collection methodology is included in the related publication. </p
Associations between antibodies to a panel of Plasmodium falciparum specific antigens and response to sub-optimal antimalarial therapy in Kampala, Uganda.
Full text linkAntibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.A cohort of children aged 1-10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.Higher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41-0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.Measurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking
Health facility data to describe the epidemiology of malaria in sub-Saharan Africa
Full text linkThe current understanding of malaria burden in Africa relies on modelled estimates based on incomplete and outdated data. The WHO defines malaria disease surveillance as a central pillar of its Global Technical Strategy. The thesis examines the precision of existing models to predict malaria burden changes and interrogation of malaria metrics from health facility and community surveys on the Kenyan coast.
Geostatistical, epidemiological models provide approximations of malaria disease burden but are rarely tested against empirical data. A systematic review included 93 health facility sites across Africa with a minimum of 5 complete years of temporal data. There was a broad congruence in the matched changes at 70 sites, but significant discordance at 23 sites which showed stagnated or upward trends.
Data on the pathway from infection to death, necessary to parametrise models of morbidity and mortality risk are rare. Prospective 12-month surveillance at six health facilities, the county hospital and repeat surveys among 36 matched communities was used to describe the epidemiology of malaria in all age groups. Despite conditions of declining transmission intensity, immunity to disease and the fatal consequences of infection continue to be acquired in early childhood, faster than anti-parasitic immunity and without evidence of emerging burdens of severe malaria or mortality among young-older non-pregnant adults.
The value of routinely collected data from health facilities to define malaria risk was explored at 36 health facility-community pairs. There was a direct non-linear polynomial relationship between passively detected fever test-positivity and traditional community-based parasite prevalence. Information obtained through routine testing of febrile patients for malaria was able to identify spatial and temporal heterogeneities of malaria risk.
Routine data offers important insights into local malaria transmission patterns, disease burdens and changing patterns of disease. An increased effort is required to replace malaria burden models with empirical data
Targeted Amplicon deep sequencing of ama1 and mdr1 to track within-host P. falciparum diversity in Kilifi, KENYA
No full textThese data were generated from targeted amplicon sequencing of Plasmodium falciparum ama1 and mdr1 genes in samples collected from Kilifi, at the coast of Kenya.
Two objectives were explored:
[1] To determine temporal changes in the genetic diversity of malaria parasites in asymptomatic and febrile infections.
[2] To track within-host parasite diversity, throughout treatment in a clinical drug trial
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Accessing complex genomic variation in Plasmodium falciparum natural infections
Full text linkGenetic polymorphism in Plasmodium falciparum is a considerable obstacle to malaria intervention. Parasites have repeatedly evolved to overcome every front-line antimalarial deployed throughout history, and artemisinin resistant populations are expanding in Southeast Asia. Promising vaccine candidates routinely fail when challenged by the genetic diversity of natural parasite populations, and a recent trial using a blood-stage antigen showed immunity was allele specific. Modern sequencing technologies have revolutionized our understanding of parasite genomics and population genetics by providing access to single nucleotide variation, but characterizing more complex polymorphism remains a key challenge. Solving this problem is important because the selective pressures from drugs and host immunity often create complex polymorphism in the most clinically relevant genes that is missed using standard genotyping methods. In three sections, this thesis is a narrative about 1) encountering complex variation, 2) overcoming it with novel tools, and then 3) innovatively applying those tools to old and new questions. I first show examples of complex variation in a vaccine candidate (EBA-175) and a drug resistance gene (pfcrt) while reporting SNP based analyses of Kenyan and Tanzanian field isolates. While introducing this complex variation I also describe biological insights discovered in these populations. In Kenya I show evidence that chloroquine resistance selects for parasites that are primaquine sensitive, use a GWAS approach to discover new drug resistance loci, and catalogue variation in known resistance genes. In Tanzania I describe the population structure and allele frequencies of parasites from two geographic regions. In the second section of the thesis I develop methods for accessing complex variation and demonstrate their utility by producing de novo assemblies of eba-175, pfcrt, ama1, and msp3.4 from thousands of sequenced samples. Finally, in the third section I apply these tools in depth to eba-175. I comprehensively characterize the SNP and structural variation in eba-175 using an alignment of 1419 de novo assemblies. I use this resource to illustrate the profiles of positive selection across the gene, and corroborate these signals of balancing selection by showing the geographic distribution of the F/C indels and a lesser known 6bp indel positioned between the DBL domains. I then use the alignments to design Sequenom genotyping assays that facilitate a genome wide association study, testing for human associations with the eba-175 indels in the infecting parasite. I close by reporting a potential association on human chromosome 14 with the 6bp indel in eba-175
Variations on the Author
Full text link“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
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