| 31. |
- Eriksson, Owen, et al.
(författare)
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Ptolemaic Metamodelling?: The Need for a Paradigm Shift
- 2013
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Ingår i: Progressions and Innovations in Model-Driven Software Engineering. - : IGI Global. - 9781466644953
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Bokkapitel (refereegranskat)abstract
- By consideration of scientific paradigm shifts, in this chapter the authors evaluate possible parallels in the evolution of modelling, and particularly metamodelling and modelling language construction, as a basis for evaluating whether or not the time is ripe for a similar change of direction in model language development for software engineering. Having identified several inconsistencies and paradoxes in the current orthodoxy, they then introduce a number of ideas from outside software engineering (including language use, philosophy, and ontology engineering) that seem to solve many of these issues. Whether these new ideas, together, are sufficient to create a shift in mindset or whether they are simply the stimulus for others to create new and orthogonal ideas remains to be seen. The authors urge the modelling and metamodelling communities to search out that new orthodoxy (i.e. instigate a paradigm shift) that will, necessarily, ensure that the science will offer simpler and more satisfying solutions in the years to come.
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| 32. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 33. |
- Gu, Fangyi, et al.
(författare)
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Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2877-2887
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.
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| 34. |
- Haiman, Christopher A., et al.
(författare)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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| 35. |
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| 36. |
- Haiman, Christopher A, et al.
(författare)
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Levels of Beta-Microseminoprotein in Blood and Risk of Prostate Cancer in Multiple Populations.
- 2012
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA common genetic variant (rs10993994) in the 5' region of the gene encoding β-microseminoprotein (MSP) is associated with circulating levels of MSP and prostate cancer risk. Whether MSP levels are predictive of prostate cancer risk has not been evaluated.MethodsWe investigated the prospective relationship between circulating plasma levels of MSP and prostate cancer risk in a nested case-control study of 1503 case subjects and 1503 control subjects among black, Latino, Japanese, Native Hawaiian, and white men from the Multiethnic Cohort study. We also examined the ability of MSP to serve as a biomarker for discriminating prostate cancer case subjects from control subjects. All statistical tests are two-sided.ResultsIn all racial and ethnic groups, men with lower MSP levels were at greater risk of developing prostate cancer (odds ratio = 1.02 per one unit decrease in MSP, P < .001 in the prostate-specific antigen [PSA]-adjusted analysis). Compared with men in the highest decile of MSP, the multivariable PSA-adjusted odds ratio was 3.64 (95% confidence interval = 2.41 to 5.49) for men in the lowest decile. The positive association with lower MSP levels was observed consistently across racial and ethnic populations, by disease stage and Gleason score, for men with both high and low levels of PSA and across all genotype classes of rs10993994. However, we did not detect strong evidence of MSP levels in improving prostate cancer prediction beyond that of PSA.ConclusionsRegardless of race and ethnicity or rs10993994 genotype, men with low blood levels of MSP have increased risk of prostate cancer.
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| 37. |
- Henderson-Sellers, Brian, et al.
(författare)
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On the Need for Identity in Ontology-Based Conceptual Modelling (Keynote Speech)
- 2015
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Ingår i: <em>Proceedings of the 11th Asia-Pacific Conference on Conceptual Modelling (APCCM 2015)</em>. - Sydney, Australien : ACS. - 9781921770470
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Konferensbidrag (refereegranskat)abstract
- Conceptual modelling is often argued to be a core technique in information systems development. An important aspect of conceptual modelling is the ontological and philosophical questions of how to conceive of object existence and identity. Despite significant interest in the topic, formal agreement on how object identity should be represented in modelling languages remains an open question. In the literature, the predominant view is that an object, or entity, is a modelling construct used to represent things. Contrary to this view, we draw on theories of language use and social ontology to understand object identity based on the notion that identity cannot be limited to the identity of physical things. The emphasis is on how language is used to create conceptual entities in a way that maintains fidelity to physical reality and ensures reliable identification of entities across domains. The theoretical implications of this work are primarily the new perspective of conceptual modelling that social ontology affords and the formal introduction and ontological grounding of institutional entities, which have so far been treated rather incidentally. Practical implications include a better foundation for designing and selecting identifiers and classes.
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| 38. |
- Henderson-Sellers, Brian, et al.
(författare)
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Situational Method Engineering
- 2014
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- While previously available methodologies for software – like those published in the early days of object technology – claimed to be appropriate for every conceivable project, situational method engineering (SME) acknowledges that most projects typically have individual characteristics and situations. Thus, finding the most effective methodology for a particular project needs specific tailoring to that situation. Such a tailored software development methodology needs to take into account all the bits and pieces needed for an organization to develop software, including the software process, the input and output work products, the people involved, the languages used to describe requirements, design, code, and eventually also measures of success or failure.The authors have structured the book into three parts. Part I deals with all the basic concepts, terminology and overall ideas underpinning situational method engineering. As a summary of this part, they present a formal meta-model that enables readers to create their own quality methods and supporting tools. In Part II, they explain how to implement SME in practice, i.e., how to find method components and put them together and how to evaluate the resulting method. For illustration, they also include several industry case studies of customized or constructed processes, highlighting the impact that high-quality engineered methods can have on the success of an industrial software development. Finally, Part III summarizes some of the more recent and forward-looking ideas.This book presents the first summary of the state of the art for SME. For academics, it provides a comprehensive conceptual framework and discusses new research areas. For lecturers, thanks to its step-by-step explanations from basics to the customization and quality assessment of constructed methods, it serves as a solid basis for comprehensive courses on the topic. For industry methodologists, it offers a reference guide on features and technologies to consider when developing in-house software development methods or customising and adopting off-the-shelf ones.
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| 39. |
- Henderson-Sellers, Brian, et al.
(författare)
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Software Modelling Languages : A Wish List
- 2015
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Ingår i: Proceedings of the Seventh International Workshop on Modeling in Software Engineering. - : IEEE Press. ; , s. 72-77
-
Konferensbidrag (refereegranskat)abstract
- Contemporary software engineering modelling tends to rely on general-purpose languages, such as the Unified Modeling Language. However, such languages are practice-based and seldom underpinned with a solid theory – be it mathematical, ontological or concomitant with language use. The future of software modelling deserves research to evaluate whether a language base that is compatible with these various elements as well as being philosophically coherent offers practical advantages to software developers.
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| 40. |
- Hendrickson, Sara J., et al.
(författare)
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Plasma Carotenoid- and Retinol-Weighted Multi-SNP Scores and Risk of Breast Cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
- 2013
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia, PA, USA : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 22:5, s. 927-936
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in beta-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. Methods: We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. Results: Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk [OR (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores = 1.04 (0.94-1.16) for beta-carotene, 1.08 (0.98-1.20) for alpha-carotene, 1.04 (0.94-1.16) for beta-cryptoxanthin, 0.95 (0.87-1.05) for lutein/zeaxanthin, and 0.92 (0.83-1.02) for retinol]. Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. Conclusions: Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. Impact: Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer. (C) 2013 AACR.
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