267 research outputs found
Improved classification of breast cancer by analysis of genetic alterations and gene expression profiling
No full textDoel van het onderzoek was betere classificatie van borsttumoren. Hugo Horlings analyseerde genetische veranderingen, zoals het aantal DNA-kopieën of het voorkomen van bepaalde mutaties, en genexpressieprofielen. Normaal borstweefsel onderscheidt zich van invasieve tumoren door verhoogde expressie van microRNA-21. Horlings gebruikte grootschalige RNA-interferentiescreening om genen op te sporen die misschien betrokken zijn bij resistentie tegen Trastuzumab (een middel gebruikt voor de behandeling van borstkanker) en ontdekte een biomarker. Wellicht kan die op termijn gebruikt worden voor identificatie van patiënten die niet reageren op Trastuzumab
Imprint of parity and age at first pregnancy on the genomic landscape of subsequent breast cancer
No full textBACKGROUND: Although parity and age at first pregnancy are among the most known extrinsic factors that modulate breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. Recent data suggest that pregnancy-induced tumor protection is different according to breast cancer subtypes, with parity and young age at first pregnancy being associated with a marked reduction in the risk of developing luminal subtype but not triple negative breast cancer. In this study, we investigated the imprint of parity and age at first pregnancy on the pattern of somatic mutations, somatic copy number alterations, transcriptomic profiles, and tumor immune microenvironment by assessing tumor-infiltrating lymphocytes (TILs) levels of subsequent breast cancer. METHODS: A total of 313 patients with primary breast cancer with available whole genome, RNA sequencing, and TILs data were included in this study. We used a multivariate analysis adjusted for age at diagnosis, pathological stage, molecular subtypes, and histological subtypes. We compared nulliparous vs. parous, late parous vs. early parous, and nulliparous vs. pregnancy-associated breast cancer (PABC) patients. Late and early parous patients were grouped by using the median age at first pregnancy. PABC was defined as patients diagnosed up to 10 years postpartum. RESULTS: Genomic alterations of breast cancer were associated with age at first pregnancy but not with parity status alone. Independently of clinicopathological features, early parous patients developed tumors characterized by a higher number of Indels (Padj = 0.002), a lower frequency of CDH1 mutations (1.2% vs. 12.7%; Padj = 0.013), a higher frequency of TP53 mutations (50% vs. 22.5%; Padj = 0.010), and MYC amplification (28% vs. 7%; Padj = 0.008). PABC were associated with increased TILs infiltration (Padj = 0.0495). CONCLUSIONS: These findings highlight an unprecedented link between reproductive history and the genomic landscape of subsequent breast cancer. We further hypothesize that TP53-mutant premalignant lesions could be less susceptible to the protective effect of an early parity, which might explain the difference of parity-induced protection according to breast cancer subtypes. This work also advocates that reproductive history should be routinely collected in future large-scale genomic studies addressing the biology of female cancers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Ruimte en milieu: Onderwerpen voor onderzoek
No full textonderzoeksbehoefte op het raakvlak van de beide beleidsvelden ruimtelijk en milieubeleid. Het resultaat is een uitgebreide lijst van onderzoeksonderwerpen op dit themaveld, waarbij het ruimtelijk perspectief voorop staat. De studie is geschreven in opdracht van het Programmeringsoverleg Ruimtelijk Onderzoek (PRO) in het kader van de voorbereidingen van het PRO voor zijn Meerjarenvisie Ruimtelijk Onderzoek 1991-1996. De Meerjarenvisie wordt opgesteld op verzoek van de Minister van VROM. De auteurs zijn werkzaam bij de Vakgroep Milieu, Natuur en Landschap, Faculteit der Beleidswetenschappen van de Katholieke Universiteit Nijmegen. Het rapport is mede tot stand gekomen dankzij de waardevolle adviezen van de klankbordgroep. Deze klankbordgroep werd, naast het PRO-secretariaat gevormd door ir. A.I.F. de Vries (lid PRO, voorzitter klankbordgroep) en de externe leden drs. A.F. van de Klundert en ir. e.G. Bos. Wij danken de leden van de klankbordgroep voor de goede samenwerking
Descriptive Statistics at Author Level for Laureates and Non-Laureates.
No full text<p>* = P<0.05—Wilcoxon Rank Sum Test of Median Difference between independent samples. The total number of sole authored papers was divided by the total number of papers for each primary author. The same was done for first author percentages, except sole authored publications were first subtracted. Authors were disambiguated with VantagePoint Software and then aggregated for each primary author.</p><p>Descriptive Statistics at Author Level for Laureates and Non-Laureates.</p
Social Business Intelligence: How and where firms can use social media data for performance measurement, an exploratory study
No full textSystems Engineering, Policy Analysis and ManagementInformation, Communication and TechnologyTechnology, Policy and Managemen
HRD-related morphology discovery in breast cancer by controlling for confounding factors
No full textLazard et al. predict homologous recombination deficiency from hematoxylin and eosin-stained slides of breast cancer tissue using deep learning. By controlling for technical artifacts on a curated dataset, the model puts forward novel HRD-related morphologies in luminal breast cancers
Author disambiguation using multi-aspect similarity indicators
No full textKey to accurate bibliometric analyses is the ability to correctly link individuals to their corpus of work, with an optimal balance between precision and recall. We have developed an algorithm that does this disambiguation task with a very high recall and precision. The method addresses the issues of discarded records due to null data fields and their resultant effect on recall, precision and F-measure results. We have implemented a dynamic approach to similarity calculations based on all available data fields. We have also included differences in author contribution and age difference between publications, both of which have meaningful effects on overall similarity measurements, resulting in significantly higher recall and precision of returned records. The results are presented from a test dataset of heterogeneous catalysis publications. Results demonstrate significantly high average F-measure scores and substantial improvements on previous and stand-alone techniques.
Academic Workforce Development: A System Dynamics based Promotion Chain Study into the Effects of Career and Funding Policies
No full textThe Dutch government supports the academic research workforce through public research funding. However, while this support is needed for continued economic growth, current trends suggest that present funding and career policies have a transitory effect on the workforce of which mainly permanent researchers benefit. In this study a model is created that describes the influence of funding regimes and career policies on the workforce development and research output over time. The model has been validated and is successful in replicating the observed historical behaviour. The model is then used to conduct several policy experiments to analyse the effect of different policies on the workforce development and research output. The model shows that the increased focus on indirect governmental funding and a temporary workforce, could have a negative impact on the workforce development and research output at public research organisations. The analysis suggest that competitive funding favours permanent staff member over temporary staff members while not inducing more research output. However, further research is needed to incorporate multiple perceptions and analyse the complex interaction between funding, workforce development and research performance.Master Systems Engineering, Policy Analysis and ManagementMulti Actor SystemsTechnology, Policy and Managemen
How accurately does output reflect the nature and design of transdisciplinary research programmes?
No full textMany of today’s societal problems are wicked problems that require a new, transdisciplinary approach in which knowledge of scientists and stakeholders from different disciplines is integrated. The evaluation of transdisciplinary science requires a multi-method approach. Bibliometric analysis is consistently among the methods in multi-method evaluations. We analyse the accuracy of bibliometric evidence for the evaluation of transdisciplinary research by examining two large climate adaptation research programmes in the Netherlands. The assessment of accuracy involves a comparison of different approaches to defining and measuring involvement, output, and quality. We draw three conclusions with regard to accuracy. First, scientific output covers a fairly high amount of the scientific activities of the programmes, though information on funding agencies is not yet sufficiently accurate to reconstruct a programme’s output through the Web of Science (WoS). Second, scientific output does not accurately reflect the nature and design of the programmes. The WoS appears to underestimate locally oriented and practically oriented research, non-academic actors rarely co-author scientific publications, and the contributions of non-academic organizations to projects could not be recognized from author affiliations. Third, our exploration of two alternative reproducible metrics (non-scientific output and download statistics) shows that it is too early to introduce such metrics into evaluation practices. The research agenda for transdisciplinary output metrics should focus on the development of a common definition of transdisciplinary research output and a typology of non-scientific outputs, as well as a discussion and assessment of the relative value of such outputs for the integration of knowledge
Abstract AP09: GENOMIC ALTERATIONS IN ENDOMETRIOSIS
No full textAbstract
BACKGROUND: Endometriosis affects ~10% of reproductive–aged women and is characterized by extra–uterine biphasic growth of uterine endometrial epithelium and stroma. Endometriosis is widely considered to be a hormonally–dependent inflammatory condition and is classified into three anatomically defined types: deep infiltrating endometriosis that locally invades pelvic organs; ovarian endometriotic cysts, and superficial peritoneal endometriosis. A clonal “precursor–cancer” link to co–occurring clear cell and endometrioid ovarian cancers has been established and somatic mutations occur in these cancer–associated endometriotic cysts, including distant benign–appearing lesions. The spectrum of genetic alteration in non–cancer associated endometriosis is not known.
METHODS: We screened a pilot series of 10 deep–infiltrating [pelvic] endometriosis lesions, without co–occurrence or history of cancer, for somatic alterations using laser captured endometrial stroma and epithelium. Two overlapping amplicon panels and digital PCR were used to validate mutations.
RESULTS: In four of ten cases we validated the presence of activating codon 12 KRAS mutations. Mutations were restricted to the epithelium and no evidence of any alterations was found in the stromal fraction.
CONCLUSIONS: We provide incontrovertible evidence of activating KRAS mutations in 40% of deep infiltrating endometriosis. This frequency of KRAS mutations is substantially higher than what has been observed in clear cell (CCOC) or endometrioid (ENOC) ovarian cancers and the occurrence of non–ovarian primary CCOC/ENOC is largely anecdotal. Our evidence suggests that these mutations represent core features of endometriosis itself, rather than a risk of malignant transformation. Overall we propose this as an opportunity to fundamentally shift the study of endometriosis to a spectrum of neoplasms. This may lead to the generation of a molecularly informed classification system and ultimately to improved prognostication and treatment.
Citation Format: Michael S. Anglesio, Tayyebeh M. Nazeran, Hugo M. Horlings, Vivian Lac, Amy Lum, Janine Senz, Julie Ho, Amy Wang, Fontayne Wong, Catherine Allaire, Christina Williams, C. Blake Gilks, Paul J. Yong, and David G. Huntsman. GENOMIC ALTERATIONS IN ENDOMETRIOSIS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP09.</jats:p
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