1,721,112 research outputs found
Genetics of primary progressive multiple sclerosis
Full text linkMultiple sclerosis (MS) patients are classified as either having relapsing onset or progressive onset disease, also known as primary progressive MS (PPMS). Relative to relapsing onset patients, PPMS patients are older at disease onset, are equally likely to be men or women, and have more rapid accumulation of disability that does not respond well to treatments used in relapsing onset MS. Although estimates vary, 5-15% of all MS patients have a PPMS disease course. Genetic variance is a proposed determinant of MS disease course. If distinct genes associated with PPMS were identified study of these genes might lead to an understanding of the biology underlying disease progression and neural degeneration that are the hallmarks of PPMS. These genes and their biological pathways might also represent therapeutic targets. This chapter systematically reviews the PPMS genetic literature. Despite the intuitively appealing notion that differences between PPMS and relapsing onset MS are due to genetics, definite differences associated with these phenotypes at the major histocompatibility complex or elsewhere in the genome have not been found. Recent large-scale genome wide screens identified multiple genes associated with MS susceptibility outside the MHC. The genetic variants identified thus far make only weak individual contributions to MS susceptibility. If the genetic effects that contribute to the differences between PPMS and relapsing MS are similar in magnitude to those that distinguish MS from healthy controls then, given the relative scarcity of the PPMS phenotype, very large datasets will be needed to identify PPMS associated genes. International collaborative efforts could provide the means to identify such genes. Alternately, it is possible that factors other than genetics underlie the differences between these clinical phenotypes
Multiple sclerosis genetics
Full text linkFamilial aggregation and the studies of twins indicate that heredity contributes to multiple sclerosis (MS) risk. Immunologic studies of leukocyte antigens subsequently followed by gene-mapping techniques identified the primary MS susceptibility locus to be within the major histocompatibility complex (MHC). The primary risk allele is HLA-DRB1*15, although other alleles of this gene also influence MS susceptibility. Other genes within the MHC also contribute to MS susceptibility. Genome-wide association studies have identified over 50 additional common variants of genes across the genome. Estimates suggest that there may be as many as 200 genes involved in MS susceptibility. In addition to these common polymorphisms, studies have identified several rare risk alleles in some families. Interestingly, the majority of the genes identified have known immunologic functions and many contribute to the risk of inheriting other autoimmune diseases. Genetic variants in the vitamin D metabolic pathway have also been identified. That vitamin D contributes to MS susceptibility as both an environmental as well as genetic risk factor underscores the importance of this metabolic pathway in disease pathogenesis. Current efforts are focused on understanding how the myriad of genetic risk alleles interact within networks to influence MS risk at family level as well as within populations
2014 Multiple Sclerosis Therapeutic Update
Full text linkRapid advances are occurring in multiple sclerosis disease modifying therapies. Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod). The impact of vitamin D supplementation on the disease course in relapsing MS patients is also being studied in several clinical trials. This article reviews the current state of the field with a forward look to the next phase of MS research that could focus on strategies to promote remyelination and provide neuronal protection
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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