1,720,977 research outputs found
Systemic inflammation and disease progression in Multiple Sclerosis
No full textMultiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by immune-mediated demyelination and neurodegeneration causing neurological and physical disability. The mechanisms leading to disease progression are not fully understood.Here it is hypothesised that systemic inflammation is associated with disease progression in MS. With this in mind, the aims of this thesis were to (1) develop a method to measure systemic inflammation longitudinally, (2) relate systemic inflammation to brain atrophy rates in MS, and (3) relate systemic inflammation to disability progression in MS. Since extracellular haemoglobin has been associated with progression in MS, a novel mechanism linking systemic inflammation and erythrocyte fragility is explored.In this thesis, my initial focus is on method development. Firstly, I show that monitoring urinary neopterin to creatinine ratio (UNCR) using ultra-performance liquid chromatography - mass spectrometry (UPLC-MS) is a useful and robust method of measuring systemic inflammation. Secondly, I show that remote physical activity monitoring can be used to track disability progression in people with progressive MS.Employing these methods, I then proceed to address the primary hypothesis in individuals with progressive MS. I find that background systemic inflammation, as measured by UNCR, and cognitive function are linked and that the magnitude of the host immune response to both symptomatic and unknown systemic inflammatory events correlates with brain atrophy rate in persons with annual brain atrophy of less than 0.4%. However, the clinical significance of this appearsviminor and there is no role for systemic inflammation in overall disability progression.In a prospective study I demonstrate that in vitro erythrocyte fragility is linked to systemic inflammation as measured by UNCR. Using UK Biobank data, I confirm an association between reticulocyte count and C-reactive protein in health and disease. Finally, I provide evidence supporting causation of haemolysis by systemic inflammation in a preclinical animal model.In summary, neurodegeneration in individuals with progressive MS may be impacted by both symptomatic and unknown, or asymptomatic, systemic inflammatory events. Further work is required to establish the importance of erythrocyte fragility in MS disease pathology and progression
Dehydration associates with lower urinary tract symptoms in progressive multiple sclerosis
No full textBackground: lower urinary tract symptoms (LUTS) are common in persons with progressive multiple sclerosis (pwPMS), who may consequently limit their fluid intake. We aimed to investigate the hypothesis that LUTS associate with objective evidence of inadequate hydration status in pwPMS.Methods: in this prospective study, 55 pwPMS were studied over 2 years. A 6-monthly first-morning urine specimen was analysed for urinary osmolality and sodium as hydration markers. LUTS symptom severity in three categories (urgency, voiding and discomfort) was assessed and quantified using a questionnaire. Correlation between LUTS severity and hydration was assessed within subjects and between subjects, controlling for age.Results: some 274 urine samples with accompanying LUTS data from 55 participants were analysed. Biochemical data showed the expected loss of urine-concentrating capacity with increasing age. Inadequate hydration was observed in 47% of participants. LUTS were very common (87% reported urgency and 89% voiding symptoms). Voiding and discomfort, but not urgency severity, were correlated with hydration markers, both within and between participants.Conclusions: LUTS are very common in pwPMS, and associate with inadequate hydration. The causes and consequences of inadequate hydration in MS need further study, since (i) this will focus greater attention on LUTS management in pwPMS and (ii) dehydration has been associated with reversible cognitive dysfunction and physical underperformance
SPoC
No full textIn clinical, field or laboratory longitudinal studies, sequential samples may need to be pooled in proportion to the time interval between sampling time points. For instance, pooling of samples in this manner provides an integration of the measurand with time over the course of the study, using analysis of a single sample. This delivers time and cost savings when compared to analysis of all the serial samples followed by area-under the curve analysis in silico. In practice the time intervals between serial samples may not be exactly the same, and there may be missing samples. The Sample Pooling Calculator (SPoC) helps with the preparation of the single pooled sample. It calculates the volume of each sample to add to the pooled sample, based on the time interval between consecutive samples. The software is written in Visual Basic for Applications (VBA) in Excel. A manual PDF is provided. SPoC is made available under a BY NC ND Creative Commons Licence
An open-source SQL database schema for integrated clinical and translational data management in clinical trials
No full textUnlocking the power of personalised medicine in oncology hinges on the integration of clinical trial data with translational data (i.e. biospecimen-derived molecular information). This combined analysis allows researchers to tailor treatments to a patient's unique biological makeup. However, current practices within UK Clinical Trials Units present challenges. While clinical data are held in standardised formats, translational data are complex, diverse, and requires specialised storage. This disparity in format creates significant hurdles for researchers aiming to curate, integrate and analyse these datasets effectively. This article proposes a novel solution: an open-source SQL database schema designed specifically for the needs of academic trial units. Inspired by Cancer Research UK's commitment to open data sharing and exemplified by the Southampton Clinical Trials Unit's CONFIRM trial (with over 150,000 clinical data points), this schema offers a cost-effective and practical 'middle ground' between raw data and expensive Secure Data Environments/Trusted Research Environments. By acting as a central hub for both clinical and translational data, the schema facilitates seamless data sharing and analysis. Researchers gain a holistic view of trials, enabling exploration of connections between clinical observations and the molecular underpinnings of treatment response. Detailed instructions for setting up the database are provided. The open-source nature and straightforward design ensure ease of implementation and affordability, while robust security measures safeguard sensitive data. We further showcase how researchers can leverage popular statistical software like R to directly query the database. This approach fosters collaboration within the academic discovery community, ultimately accelerating progress towards personalised cancer therapies
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
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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
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