1,721,056 research outputs found
Cancer risks for people with colorectal cancer-predisposing genetic mutations
No full text© 2013 Dr. Aung Ko WinBackground: Colorectal cancer is one of the most frequently diagnosed cancers in the world. On average, 1 in 20 people will be diagnosed with colorectal cancer in their lifetime. However, an individual’s risk of colorectal cancer varies greatly depending on their genetic and environmental factors. One of the strongest risk factors for colorectal cancer is inherited mutations in predisposing genes such as DNA mismatch repair genes (Lynch syndrome), and DNA base excision repair gene, MUTYH. Given the availability and effectiveness of colorectal cancer screening and interventions, we need precise and accurate risks of cancers to reduce the burden of disease by targeting preventive measures to those at highest risk. The overall aim of the thesis was to estimate cancer risks for people with colorectal cancer-predisposing genetic mutations and their relatives.
Methods: For the systematic reviews (Chapters 3, 4 and 8), PubMed was used to search for relevant studies. To address the different research questions (Chapters 5, 6, 7, 9, 10 and 11), appropriate study samples were selected from the Colon Cancer Family Registry, an international consortium of 37,041 participants from 10,375 colorectal cancer families recruited from the USA, Canada, Australia and New Zealand. Prospective cohort analysis (Chapter 5), retrospective cohort analyses (Chapter 6, 7 and 11), weighted cohort analysis (Chapter 9) and modified segregation analysis (Chapter 10) were conducted.
Results: There was no model that sufficiently covers the known risk factors for colorectal cancer that is suitable for assessment of people from across the full range of risk (Chapter 3). The existing statistical models (MMRpro, PREMM, MMRpredict, and Leiden) had similar discrimination and were quite sensitive and specific in predicting mismatch repair gene mutations (Chapter 4). People with mismatch repair gene mutations without a prior diagnosis of cancer had an increased risk of cancers that are previously known to be associated with Lynch syndrome as well as pancreatic and breast cancers (Chapter 5). There was no evidence of their non-carrier relatives having an increased risk of any cancer, including colorectal cancer (Chapter 5). People with mismatch repair gene mutations with a prior diagnosis of colorectal cancer (Chapter 6) or endometrial cancer (Chapter 7) had substantially elevated risk for a greater range of cancers including breast and prostate cancers.
About half of breast cancer tumours in mismatch repair gene mutation carriers showed loss of mismatch repair proteins, indicating a significant likelihood of an underlying germline mutation (Chapter 8). For all mismatch repair gene mutation carriers combined, there was no evidence of an association of colorectal cancer with the 11 genetic variants that are known to be associated with colorectal cancer for the general population (Chapter 9). There was a wide variation of colorectal cancer risk for monoallelic MUTYH mutation carriers depending on their family history, and their risk can be sufficiently high to warrant consideration of more intensive colorectal cancer screening than for the general population (Chapter 10). Risk of colorectal cancer for first-degree relatives of colorectal cancer cases with suspected Lynch syndrome was higher than for first-degree relatives of mismatch repair-proficient colorectal cancer cases (Chapter 11). A greater risk of colorectal cancer was estimated for first-degree relatives if colorectal cancer cases were diagnosed before age 50 years, had proximal colon cancer, or if their tumours had expanding tumour margin, peritumoural lymphocytes, tumour-infiltrating lymphocytes, or synchronous tumour (Chapter 11).
Conclusions: These accurate and precise cancer risk estimates are critically important to guide and inform public health guidelines, such as for cancer screening; and clinical management of cancer families. The studies from this thesis are fundamental for the development of a new comprehensive model for colorectal cancer risk prediction that takes into account all risk factors for colorectal cancer and is suitable for assessment of people from across the full range of risk
Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis
No full textOur aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, especially if at a young age, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992-99 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up=15.7; range=0.8-21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (P<.001), similar if they survived to 5 years (P=0.4), and lower if they survived to 10 years (P=0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR)=2.52 [95% CI:2.11-3.01] per 10 nodes) and tumor grade (HR=1.62 [95% CI:1.34-1.96] per grade). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis
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
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