1,721,387 research outputs found
Microsatellite instability/mismatch repair deficiency in pancreatic cancers: the same or different?
No full textNo abstract availabl
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
GERMLINE & SOMATIC VARIATION IN GASTROINTESTINAL MALIGNANCIES
Full text linkGermline Somatic Variation in Gastrointestinal Malignancies
Ashton Antoine Connor
Doctor of Philosophy
Institute of Medical Science (IMS)
University of Toronto
2017
Abstract
Primary gastrointestinal malignancies have among the highest incidence, morbidity and mortality rates. We hypothesized that improved understanding of predisposing germline variation and acquired somatic variation would inform novel prevention and treatment strategies. We generated germline and somatic DNA and RNA sequence data from colorectal and pancreatic cancer patients.
For the germline, we identified non-silent variation occurring at allele frequencies of less than 1% in the general population in a gene, FAT1, which co-segregates with colorectal adenocarcinoma by exome sequencing of affecteds in pedigrees that meet Familial Colorectal Cancer Type X criteria obtained from Canadian and Australian databases. This observation was not validated by targeted sequencing of affected probands or by a genetically modified mouse model.
For the somatic, we identified genomic signatures that describe mutational processes acting on pancreatic ductal adenocarcinomas and transcriptomic signatures that describe the immune component of the tumour-associated stroma by whole genome and transcriptome sequencing of a retrospective cohort of surgically resected specimens. We integrated the two signature types, demonstrating that pancreatic cancers with deficiencies in DNA repair, namely mismatch repair and homologous recombination, were associated with high expression of transcripts representative of active adaptive immunity and co-regulatory pathways.
We also studied three separate pancreatic ductal adenocarcinomas that presented in one patient, two of which arose following resection of the primary cancer. By whole genome sequencing, we demonstrated that these secondary lesions were in fact intra-parenchymal metastases sharing a common ancestor with the primary, rather than distinct metachronous lesions arising from separate tumour lineages. The degrees of genomic concordance between the primary and two secondary samples were characterised to determine the molecular phylogeny of the three lesions. Clinically, this informs patient management, as resection of metastatic pancreas cancer is unlikely to result in meaningful disease control. Scientifically, this allows the study of primaries and metastases in a system independent of external selective pressures.
Overall, we have identified novel somatic findings in pancreas cancer that will hopefully inform patient management, and we have created germline and somatic repositories of sequencing data from which future investigations of genetic variation can be performed.Ph.D
Identifying Susceptibility Genes for Familial Pancreatic Cancer Using Novel High-resolution Genome Interrogation Platforms
No full textFamilial Pancreatic Cancer (FPC) is a cancer syndrome characterized by clustering of pancreatic cancer in families, but most FPC cases do not have a known genetic etiology. Understanding genetic predisposition to pancreatic cancer is important for improving screening as well as treatment. The central aim of this thesis is to identify candidate susceptibility genes for FPC, and I used three approaches of increasing resolution. First, based on a candidate-gene approach, I hypothesized that BRCA1 is inactivated by loss-of-heterozygosity in pancreatic adenocarcinoma of germline mutation carriers. I demonstrated that 5/7 pancreatic tumors from BRCA1-mutation carriers show LOH, compared to only 1/9 sporadic tumors, suggesting that BRCA1 inactivation is involved in tumorigenesis in germline mutation carriers. Second, I hypothesized that the germline genomes of FPC subjects differ in copy-number profile from healthy genomes, and that regions affected by rare deletions or duplications in FPC subjects overlap candidate tumor-suppressors or oncogenes. I found no significant difference in the global copy-number profile of FPC and control genomes, but I identified 93 copy-number variable genomic regions unique to FPC subjects, overlapping 88 genes of which several have functional roles in cancer development. I investigated one duplication to sequence the breakpoints, but I found that this duplication did not segregate with disease in the affected family. Third, I hypothesized that in a family with multiple pancreatic cancer patients, genes containing rare variants shared by the affected members constitute susceptibility genes. Using next-generation sequencing to capture most bases in coding regions of the genome, I interrogated the germline exome of three relatives who died of pancreatic cancer and a relative who is healthy at advanced age. I identified a short-list of nine candidate genes with unreported mutations shared by the three affected relatives and absent in the unaffected relative, of which a few had functional relevance to tumorigenesis. I performed Sanger sequencing to screen an unrelated cohort of approximately 70 FPC patients for mutations in the top two candidate genes, but I found no additional rare variants in those genes. In conclusion, I present a list of candidate FPC susceptibility genes for further validation and investigation in future studies.Ph
- …
