Quantitative Factors Proposed to Influence the Prevalence of Canine Tick-Borne Disease Agents in the United States

The Companion Animal Parasite Council hosted a meeting to identify quantifiable factors that can influence the prevalence of tick-borne disease agents among dogs in North America. This report summarizes the approach used and the factors identified for further analysis with mathematical models of canine exposure to tick-borne pathogens

Tick-, mosquito-, and rodent-borne parasite sampling designs for the National Ecological Observatory Network

Parasites and pathogens are increasingly recognized as significant drivers of ecological and evolutionary change in natural ecosystems. Concurrently, transmission of infectious agents among human, livestock, and wildlife populations represents a growing threat to veterinary and human health. In light of these trends and the scarcity of long-term time series data on infection rates among vectors and reservoirs, the National Ecological Observatory Network (NEON) will collect measurements and samples of a suite of tick-, mosquito-, and rodent-borne parasites through a continental-scale surveillance program. Here, we describe the sampling designs for these efforts, highlighting sampling priorities, field and analytical methods, and the data as well as archived samples to be made available to the research community. Insights generated by this sampling will advance current understanding of and ability to predict changes in infection and disease dynamics in novel, interdisciplinary, and collaborative ways. (Résumé d'auteur

Tick-, Mosquito-, and Rodent-Borne Parasite Sampling Designs for the National Ecological Observatory Network [Special Feature: NEON Design]

Parasites and pathogens are increasingly recognized as significant drivers of ecological and evolutionary change in natural ecosystems. Concurrently, transmission of infectious agents among human, livestock, and wildlife populations represents a growing threat to veterinary and human health. In light of these trends and the scarcity of long-term time series data on infection rates among vectors and reservoirs, the National Ecological Observatory Network (NEON) will collect measurements and samples of a suite of tick-, mosquito-, and rodent-borne parasites through a continental-scale surveillance program. Here, we describe the sampling designs for these efforts, highlighting sampling priorities, field and analytical methods, and the data as well as archived samples to be made available to the research community. Insights generated by this sampling will advance current understanding of and ability to predict changes in infection and disease dynamics in novel, interdisciplinary, and collaborative ways

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

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Investigating the Adoption of Clinical Genomics in Australia. An Implementation Science Case Study

Despite the overwhelming interest in clinical genomics, uptake has been slow. Implementation science offers a systematic approach to reveal pathways to adoption and a theory informed approach to addressing barriers presented. Using case study methodology, we undertook 16 in-depth interviews with nongenetic medical specialists to identify barriers and enablers to the uptake of clinical genomics. Data collection and analysis was guided by two evidence-based behaviour change models: the Theoretical Domains Framework (TDF), and the Capability, Opportunity Motivation Behaviour model (COM-B). Our findings revealed the use of implementation science not only provided a theoretical structure to frame the study but also facilitated uncovering of traditionally difficult to access responses from participants, e.g., “safety in feeling vulnerable” (TDF code emotion/COM-B code motivation). The most challenging phase for participants was ensuring appropriate patients were offered genomic testing. There were several consistent TDF codes: professional identity, social influences, and environmental context and resources and COM-B codes opportunity and motivation, with others varying along the patient journey. We conclude that implementation science methods can maximise the value created by the exploration of factors affecting the uptake of clinical genomics to ensure future interventions are designed to meet the needs of novice nongenetic medical specialists

Lifelong learning and teacher education

In 2001 this project was undertaken by members of the Centre for Lifelong Learning at [the] Australian Catholic University. The authors were concerned to understand the ways in which lifelong learning was conceptualised in Australian teacher education. Their investigation sought to determine how teacher educators’ roles and responsibilities might change in response to the policy challenge of making lifelong learning a reality for all. The project had three broad goals: to examine the policies, principles and practices that are shaping the roles and responsibilities of teacher educators as they seek to make lifelong learning a reality for all; to identify and analyse changed roles and responsibilities for teacher educators resulting from the current emphasis on lifelong learning; and to project the implications for Governments, employing authorities, schools and Faculties of Education as they seek to enable teacher educators to make lifelong learning a reality. The report presented the case study findings. It outlined examples of ‘good practice’ in the key areas of: curriculum and new conceptions of knowledge; learning, teaching and information and communication technology; leading and managing; partnerships and pathways; and standard setting, assessment, reporting and evaluation. Data gathered in the course of the project was collated and an analysis conducted to devise an Action Plan for operationalising lifelong learning in Australian teacher education. The project was funded by the Department of Education, Training and Youth Affairs under the Evaluation and Investigation Program (EIP)