Transformative research as knowledge mobilization: transmedia, bridges and layers

Mainstream knowledge production and communication in the academy generally reflect the tenets of positivist research and predominantly embody hierarchical processes of knowledge transfer. In contrast, a transformative research paradigm is rooted in knowledge mobilization processes involving close collaboration between researchers and community actors as co-enquirers as a part of a broader agenda for progressive social change. They also involve strategic communication strategies that mobilize knowledge beyond those directly involved in the research process. We illustrate the cyclical pattern and transgressive potential of knowledge mobilization processes through a reflective case study of a participatory action research program in the Canadian Prairies. Based on this work, we present three key knowledge mobilization strategies. These include: using transmedia to exchange knowledge across a range of communication media; building bridges to invite communication amongst diverse knowledge communities; and layering to communicate knowledge at varying levels of detail. We critically examine our own practice as a contested and partial process in tension with the institutional and cultural durability of the more linear knowledge transfer paradigm. Knowledge mobilization strategies provide a framework to implement research methods, communication processes, and outcomes that are high in impact and relevant in struggles for a more just and resilient society. </jats:p

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Experts’ knowledge renewal and maintenance actions effectiveness in high-mix low-volume industries, using Bayesian approach

International audienceIncreasing demand diversity have resulted in high-mix low-volume production where success depends on our ability to quickly design and develop new products. This requires sustainable production capacities and efficient equipment utilization which is ensured through appropriate maintenance strategies. At present, these are derived from experts' knowledge, capitalized in FMECA (Failure Mode, Effect and Criticality Analysis) and/or maintenance procedures. (Abu-Samah et al. 2015) found increasing unscheduled breakdowns, failure durations and number of repair actions in each failure as the key challenges while sustaining production capacities in complex production environment. This is an evidence that maintenance based on the historical knowledge is not always effective to cope up with an evolving nature of equipment failure behaviors. Therefore, in this paper, we present an operational methodology based on Bayesian approach and an extended FMECA method to support experts' knowledge renewal and maintenance actions effectiveness. In the proposed methodology, we capitalize and model experts' existing knowledge from FMECA files as an operational Bayesian network (O-BN) to provide real time feedback on poorly executed maintenance actions. The accuracy of O-BN is monitored through drift in maintenance performance measurement (MPM) indicators that results in learning an unsupervised Bayesian network (U-BN) to discover new causal relations from historical data. The structural difference between O-BN and U-BN highlights potential new knowledge which is validated by experts prior to modify existing FMECA and associated maintenance procedures. The proposed methodology is evaluated in a well reputed high-mix low-volume semiconductor production line to demonstrate its ability to dynamically renew experts' knowledge and improve maintenance actions effectiveness

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants