1,721,003 research outputs found
How to adjust for baseline heterogeneity in count data occurring from experimental studies
No full textWhen analysing the results from experimental and observational studies, the main aim is often to estimate what effect the treatment is having on the participant. For this reason, it is important that the estimate for the treatment effect is not influenced (biased) by having imbalanced (heterogeneous) treatment groups. Randomisation is often used in experimental studies to obtain homogenous treatment groups i.e. the distribution of all covariates (except treatment group) is the same between treatment groups. However, when the sample size is small, randomisation may not successfully obtain entirely homogeneous groups. Heterogeneous groups are often an issue in observational studies as randomisation cannot be used. This thesis aims to demonstrate the need to adjust for baseline heterogeneity by showing the potential consequences of not. The thesis also aims to find a method to successfully adjust for baseline heterogeneity. A hypothetical example is drawn up to demonstrate the potential bias in the results if no adjustment for the baseline heterogeneity is made. An explanation is given on how failing to adjust for heterogeneity, could lead to false conclusions to the extent that a harmful drug could be wrongly authorised. This thesis examines the properties of six potential methods for adjusting for baseline heterogeneity which include 5 parametric methods (using an Offset, Continuous Covariate, Categorical Covariate, Random Effect and a Conditional model) and a non-parametric method (Mantel-Haenszel). The ability of these methods to adjust for heterogeneity is assessed by using them to analyse three datasets containing baseline heterogeneity. Furthermore, a detailed simulation study is undertaken to analyse the bias and RMSE of each of the methods. The treatment effects obtained from the different methods (for adjusting for baseline heterogeneity) differ in the analysis of the example datasets. The AIC and BIC demonstrate that adjusting for baseline heterogeneity is required. However, the AIC and BIC cannot convincingly separate the parametric methods (AIC and BIC is not available for the Mantel Haenszel method). In order to distinguish between the 6 different trial methods, simulation studies are used. The RMSE is then calculated for a range of different scenarios (different sample sizes, risk ratios, number of treatment groups and time points). The Continuous method consistently performs well. For this reason, the 13 Continuous method appears to be the preferred method to use
Haptoglobin as a novel treatment for subarachnoid haemorrhage
No full textSubarachnoid haemorrhage (SAH) is a severe neurological condition caused by rupture of an intracranial aneurysm. A clot forms in the subarachnoid space and erythrocyte lysis causes haemoglobin (Hb) to accumulate in the CSF. In patients surviving the initial bleed, secondary complications such as vasospasm and delayed ischaemic neurological deficits (DIND) can result in poor long term outcome. Hb is neurotoxic through oxidative mechanisms and has also been implicated in the pathogenesis of vasospasm. Management of SAH patients is aimed at securing the aneurysm, inhibiting vasospasm and diversion of CSF to treat hydrocephalus; high morbidity means novel treatments to improve long term outcome are needed and there are none targeting Hb toxicity. Haptoglobin (Hp) is responsible for binding to cell free Hb, facilitating scavenging by CD163-positive macrophages. Hp inhibits free Hb’s pro-oxidative potential by shielding the redox active iron contained in the haem group, rendering Hb oxidatively inert. Two co-dominant HP alleles (HP1 and HP2) exist in humans as a result of an intragenic duplication event. This lead to the production of dimers in HP1 homozygotes (HP1-1), dimers and trimers in heterozygotes (HP2-1), and finally tetramers and large polymers in HP2 homozygotes (HP2-2). Hp isoforms differ in their expression levels, their ability to inhibit Hb’s oxidative potential, and when in complex with Hb, their affinity for CD163 and uptake by macrophages. In this study I hypothesized that: haptoglobin affects outcome after subarachnoid haemorrhage through its role in haemoglobin scavenging and haptoglobin supplementation after SAH is of therapeutic benefit. The aims were to: 1) investigate if HP genotype influences outcome after SAH via its role in Hb scavenging, 2) characterise the kinetics of Hb scavenging in the two week period after SAH, 3) establish whether Hp can reverse Hb neurotoxicity in vitro, and 4) establish and characterise an in vivo model of SAH to translate the results of the in vitro experiments. Due to differential Hb scavenging function, it was hypothesized that HP genotype impacts on outcome after SAH. 1299 SAH patients were typed for their HP duplication genotype and the single nucleotide polymorphism rs2000999, the largest genetic contributor to Hp expression level. Logistic regression analysis of long term outcome identified no effect of rs2000999 but the Hp duplication affected outcome, implying mediation through Hp function rather than expression level. HP2-2 was associated with favourable outcome in high Fisher grade patients (grades III and IV, Odds Ratio (OR): 2.4, 95% Confidence Intervals (CI) 1.4-.4.3, p=0.007). To seek further mechanistic evidence for the effect of Hp on outcome after SAH, the kinetics of Hb and Hp was investigated in serial cerebrospinal fluid (CSF) samples from 44 Fisher grade III-IV SAH patients during a two week period post-ictus. Total Hb levels increased gradually, reaching a plateau of 11.5µM (median between days 11 and 13, interquartile range (IQR): 2.1-16.2µM); the majority of this Hb was found to be uncomplexed (median 96.3%, (IQR): 83.3-99.4%, from third day onwards). There was a trend towards an association of high uncomplexed Hb levels with worse outcome (modified Rankin Scale (mRS) at 6 months post-ictus) (OR: 0.7, 95% CI 0.5-1.0, p=0.064). Auto-oxidation of Hb can cause oxidative damage which inhibits complex formation by Hp. Exogenous Hp was added to the CSF, enough to saturate all Hb, to investigate how much Hb was still able to bind Hp; 90.6% (IQR: 65.8- 96.5%) of the uncomplexed Hb was able to form complexes with exogenous Hp. The Hb scavenging ability of Hp isoforms was investigated with linear mixed modelling. Significantly lower levels of uncomplexed Hb were associated with the Hp2-2 phenotype (p=0.03, vs Hp1-1), in keeping with improved Hb scavenging due to Hp2-2’s higher valency for Hb. To test if Hp can protect against Hb neurotoxicity, primary hippocampal neurones from C57BL/6 mouse pups were cultured and treated with Hb, Hb+Hp, Hp or vehicle. Following a week in culture, viable neurones were counted. Hb produced a dose dependent cytotoxic effect (pSignificantly lower levels of uncomplexed Hb were associated with the Hp2-2 phenotype (p=0.03, vs Hp1-1), in keeping with improved Hb scavenging due to Hp2-2’s higher valency for Hb. To test if Hp can protect against Hb neurotoxicity, primary hippocampal neurones from C57BL/6 mouse pups were cultured and treated with Hb, Hb+Hp, Hp or vehicle. Following a week in culture, viable neurones were counted. Hb produced a dose dependent cytotoxic effect (p=0.003). No adverse effects on neuronal viability were observed with Hp alone. To translate the in vitro findings, I established in our laboratory an in vivo murine model of SAH, involving a stereotaxic injection of blood into the pre-chiasmatic cistern of C57BL/6 mice. The model was optimized to refine the technique, to prepare for future experiments testing Hp as a therapeutic agent after experimental SAH.<br/
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
FIGURE 16 in A story of nasal horns: two new subspecies of Iguana Laurenti, 1768 (Squamata, Iguanidae) in Saint Lucia, St Vincent & the Grenadines, and Grenada (southern Lesser Antilles)
No full textFIGURE 16. STRUCTURE bar plot showing admixture coefficient of each individual to the three inferred genetic clusters. This bar plot was produced using the DISTRUCT program (Rosenberg 2004).Published as part of Breuil, Michel, Vuillaume, Barbara, Schikorski, David, Krauss, Ulrike, Morton, Matthew N., Haynes, Pius, Daltry, Jennifer C., Corry, Elizabeth, Gaymes, Glenroy, Gaymes, Joanne, Bech, Nicolas, Jelić, Mišel & Grandjean, Frédéric, 2019, A story of nasal horns: two new subspecies of Iguana Laurenti, 1768 (Squamata, Iguanidae) in Saint Lucia, St Vincent & the Grenadines, and Grenada (southern Lesser Antilles), pp. 201-232 in Zootaxa 4608 (2) on page 223, DOI: 10.11646/zootaxa.4608.2.1, http://zenodo.org/record/305518
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
- …
