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The epidemiology, risk factors and diagnosis of neonatal sepsis
Get PDFA thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of
Doctor of Philosophy
Johannesburg, South Africa 2017.Background: In sub-Saharan Africa, sepsis is the third most common cause of deaths during the neonatal period. Both maternal human immunodeficiency virus (HIV) infection and vitamin D deficiency (VDD) have been identified as risk factors for infection in children. The relationship of these risk factors, especially VDD among neonates in developing countries is not well documented. The “gold” standard to diagnose sepsis is blood culture; however, it has low sensitivity. Therefore there is a need for tests with improved sensitivity, to improve estimates of the incidence and aetiology of neonatal sepsis. This could enable prompt and targeted use of antibiotics to reduce both mortality and mitigate against emergence of antimicrobial resistance. The aims of this study were to determine the epidemiology of early-onset sepsis (EOS) and community acquired sepsis (CAS) using standard blood culture. Further, we evaluated the role of molecular diagnostic using polymerase chain reaction (PCR) based technology (Taqman array card), and evaluated role of maternal HIV infection and vitamin D status as risk factors for EOS and CAS in neonates born in Soweto, South Africa.
Methods and Procedures: Neonates born and/ or admitted with a diagnosis of possible serious bacterial infection (pSBI) with no previous hospital admission were prospectively enrolled into the study. They were grouped into EOS (onset of sepsis before 3 days of life) and CAS (onset of sepsis between 3-27 days of life). A subgroup of patients who met a predetermined definition of clinical or culture confirmed neonatal sepsis (protocol-defined sepsis), had blood and naso/oro-pharyngeal (NPOP) swabs tested using a PCR- based technique, Taqman array card (TAC) to identify possible causative pathogens. Healthy neonates were enrolled as controls, matched for age-group of cases with sepsis. In a separate cohort, mother-newborn dyads were enrolled soon after birth, and had blood taken to measure serum 25-hydroxyvitamin D [25(OH)D]. These newborns were grouped as being healthy or ill with sepsis. Sepsis in this cohort was defined as presence of clinical signs together with the presence of a positive blood culture and/or high C-reactive protein or interleukin-6. For both cohorts, cases and controls were stratified according to HIV exposure.
Results: There were 34,808 live births in Soweto over the study period, August 2013 to September 2014. A total of 3260 neonates were enrolled, 2624 (80%) and 636 (20%) with a diagnosis of early-onset pSBI (EO-pSBI) and community acquired pSBI (CA-pSBI) respectively. Blood culture positivity rate due to pathogens in neonates with EO-pSBI was 3.7% (96/2624). The incidence (per 1000 live births) of EO-pSBI was 106 (95%CI 102-109
and 3.8 (95% CI 3.2-4.6) for culture-confirmed EOS. More than two thirds of putative pathogens isolated from neonates with culture-confirmed EOS (69.8%) were Gram positive bacteria. The common bacteria were Group B streptococcus (GBS; 35/105; 33%) , Viridans streptococcus (23/105; 22%), Enterococcus species (10/105; 10%) and Escherichia coli (E. coli; 10/105; 10%), with incidences (per 1000 live births) of 1.41 (95%CI 1.06-1.86), 0.92 (95%CI 0.65-1.30), 0.40 (95% CI 0.20-0.61) and 0.40 (95% CI 0.20-0.61) respectively. HIV exposed neonates had higher incidence of sepsis than HIV unexposed for EO-pSBI (OR:1.45; 95%CI 1.34-1.56). The overall case fatality rate was 9.0% (236/2624) for EOS. Blood culture positivity rate due to pathogens in neonates with CA-pSBI was 9% (55/636). The incidence of CA-pSBI and blood/CSF culture confirmed CAS were 33.4 (95%CI 31.6-35.4) and 3.53 (95%CI 2.96-4.22), respectively. More than three-quarters (76.7%) of putative pathogens isolated from CA-pSBI were Gram positive bacteria. Among, the culture-confirmed CAS, common organisms in blood were Viridans streptococci (17/60; 28%), GBS (14/60; 23%), Staphylococcus aureus (12/60; 20%), and E.coli (9/60; 15%); while in CSF the common organisms were GBS (9/25; 36%), Staphylococcus aureus (5/25; 20%), Viridans streptococcus (4/25; 16%) and Enterococcus species (4/25; 16%). The overall incidence for common organisms in blood and/ or CSF for CAS were 0.95 (95%CI 0.67-1.33), 0.90 (95%CI 0.63-1.27), 0.75 (95%CI 0.51-1.10) and 0.58 (95%CI 0.37-0.89) for Staphylococcus aureus, Viridans streptococcus, GBS and Enterococcus species respectively. HIV exposed neonates had higher incidence of blood/CSF culture confirmed CAS than HIV unexposed (OR:1.90;95%CI 1.32-2.74), including specifically for Staphylococcus aureus (OR:2.71; 95% CI 1.35-5.41), GBS (OR:4.82; 95%CI 2.13-10.9) and E.coli (OR:2.71; 95%CI 1.07-6.82). . The case fatality rate for CAS was 1.4% (9/636).
Among protocol-defined sepsis cases tested with TAC, bacteria or viruses were detected in blood in 37.1% of cases with EOS. Although similar organisms were identified in blood of cases and controls, proportion of cases with positive TAC was higher than in controls (37.1% vs 19.5%; OR: 2.35; 95%CI 1.72-3.21). The common organisms identified in blood of EOS cases using TAC were Streptococcus pneumoniae (14.2%), Ureaplasma species (9.2%), Pseudomonas species (8.5%) and GBS (7.0%). In pharyngeal swabs there were fewer cases that tested positive with TAC compared to controls (44.1% vs 53.1%; OR:0.69; 95%CI 0.59-0.90), and the common organisms identified in cases were Ureaplasma species (19.9%), Klebsiella pneumoniae (11.9%) and GBS (8.5%). After applying modelling factoring positive blood culture, one was able to attribute aetiology to a specific pathogen for 26.7% of cases using blood culture and TAC, and therefore 73.3% of cases did not have an identifiable aetiology from the pathogens tested in culture or TAC. Among the positive TAC results in blood and pharyngeal swabs the organisms that were found to be attributable to EOS were Ureaplasma species (5.4%, 95% CI 3.6%-5.1%) , GBS (4.8%, 95%CI 4.1%-5.8%), and Viridans streptococcus (4.2%, 95%CI 3.5%-5.1%). There were no differences in number of cases and controls with positive TAC results between HIV exposed and unexposed neonates.
In neonates with CAS protocol-defined sepsis cases tested with TAC, bacteria or viruses were detected in blood in 45.8% of cases. Proportion of cases with positive TAC in blood was higher than in controls (45.8% vs 27.4%; OR: 2.24; 95%CI 1.30-3.86). The common organisms identified included Streptococcus pneumoniae (15.7%), GBS (14.5%) and E. coli (8.3%). In pharyngeal swabs there were no differences in numbers with positive TAC results between cases and controls (75.0% vs 70.1%, OR:1.28; 95%CI 0.77-2.12), and the common organisms identified in cases were GBS (28.0%), Klebsiella pneumoniae (24.2%) and at equal rates (13.6%) were E. coli, Ureaplasma species and Streptococcus pneumoniae. Viruses were identified in 40% of cases in the pharyngeal swabs. There were no differences in number of cases and controls with positive TAC results between HIV exposed and unexposed neonates.
Maternal and cord blood 25(OH)D levels were 54.7±30.1 and 39.0±21.3 nmol/L respectively, and prevalence of VDD (defined as a 25(OH)D level of <30 nmol/L) among the women and their newborns was 18.8% and 39.8% respectively. There were no significant differences in 25(OH)D levels or VDD between HIV infected and uninfected pregnant women. On multivariate analysis VDD in neonates was not associated with EOS.
Conclusions: There is high burden of neonatal sepsis in Soweto, including significant mortality. Based on blood culture, GBS is the most common pathogen causing EOS; Viridans streptococcus and Staphylococcus aureus the most common causes of culture-confirmed CAS. HIV exposure contributes significantly to a higher burden of bacterial sepsis in neonates. Although molecular detection using the TAC assay identified more bacteria organisms than from blood culture, including non-culturable organisms like Ureaplasma species, its use as a diagnostic tool for sepsis warrants further evaluation due to high positivity rates among healthy neonates for many of the targeted organisms in blood and NPOP swabs. Nevertheless, after correcting for positive controls, a combination of blood culture and TAC improved the detection of organisms in neonates with sepsis. In this study, maternal and newborn VDD was not associated with sepsis; however, this warrants further evaluation since this study had a limited number of neonates with culture confirmed disease.LG201
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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