The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing

Genomic sequencing technology is moving rapidly from the research setting into clinical medicine but significant technological and interpretive challenges remain. Whole exome sequencing (WES) in its recent clinical application provides a genetic diagnosis in about 25% of cases (Berg 2014). While this diagnostic yield is substantial, it also indicates that in a majority of cases, patients are receiving negative results (i.e., no explanatory genetic variant found) from this technology. There are a number of uncertainties regarding the meaning of a negative result in the current context of WES. A negative result may be due to current technological limitations that hinder detection of disease-causing variants or to gaps in the knowledge base that prohibit accurate interpretation of their pathogenicity; or it may indicate that there is not a genetic etiology for the disorder. In this paper we examine the uncertainties and nuances of the negative result from genome sequencing and how both clinicians and patients make meaning of it as revealed in ethnographic observations of the clinic session where results are returned, and in interviews with patients. We find that clinicians and patients construct the meaning of a negative result in ways that are uncertain, contingent, and multivalent; but invested with optimism, promise, and potentiality

Referencing Sources of Molecular Spectroscopic Data in the Era of Data Science: Application to the HITRAN and AMBDAS Databases

The application described has been designed to create bibliographic entries in large databases with diverse sources automatically, which reduces both the frequency of mistakes and the workload for the administrators. This new system uniquely identifies each reference from its digital object identifier (DOI) and retrieves the corresponding bibliographic information from any of several online services, including the SAO/NASA Astrophysics Data Systems (ADS) and CrossRef APIs. Once parsed into a relational database, the software is able to produce bibliographies in any of several formats, including HTML and BibTeX, for use on websites or printed articles. The application is provided free-of-charge for general use by any scientific database. The power of this application is demonstrated when used to populate reference data for the HITRAN and AMBDAS databases as test cases. HITRAN contains data that is provided by researchers and collaborators throughout the spectroscopic community. These contributors are accredited for their contributions through the bibliography produced alongside the data returned by an online search in HITRAN. Prior to the work presented here, HITRAN and AMBDAS created these bibliographies manually, which is a tedious, time-consuming and error-prone process. The complete code for the new referencing system can be found at \url{https://github.com/hitranonline/refs}.Comment: 11 pages, 5 figures, already published online at https://doi.org/10.3390/atoms802001

Prevalence and perceptions of food insecurity and coping strategies in Fort Albany First Nation, Ontario

Background: Food insecurity has been described as an urgent and pervasive public health issue for Aboriginal people (First Nations [FN], Métis, and Inuit) in Canada. However, national health surveys have generally excluded a large portion of the Aboriginal population (FN living on-reserve and Inuit), resulting in limited data on food insecurity in these individuals and communities. In addition, scales for measuring food insecurity have not been validated in Canadian Aboriginal populations. Food security challenges faced by Aboriginal people living in remote communities are unique and few studies have examined the perceptions of and coping strategies for food insecurity in this population. Objectives: The overall objective of this research was to explore various aspects of food insecurity (prevalence, perceptions, and coping strategies) in the remote, on-reserve First Nations community of Fort Albany, Ontario. This thesis consisted of five studies conducted in Fort Albany. The objectives for Study I were to quantitatively measure the prevalence of food insecurity using the Household Food Security Survey Module (HFSSM) and to use two qualitative interview questions to evaluate the relevance of the HFSSM. Study II used qualitative interview questions to examine the perceptions of and coping strategies for food insecurity. Studies III and IV investigated two programs in Fort Albany that had the potential to affect food security: the school snack program and a greenhouse project. Study III assessed the impact of the school snack program on student food intake. Study IV was a descriptive case study of the context and implementation of a community greenhouse project. Study V involved the development and formative evaluation of supplemental questions for the HFSSM intended to be relevant for measuring food security in First Nations households. Methods: One adult from each household in the community was invited to complete the 18-item HFSSM, demographic questions, and an interview with questions on the relevance of the HFSSM for First Nations food security and strategies used to cope with food insecurity. To evaluate the snack program, 24 hour diet recall data were collected using the Waterloo Web-based Eating Behaviour Questionnaire (WEB-Q) in November 2004 and December 2007 with grade six to 10 students attending Peetabeck Academy in Fort Albany. Food group consumption and nutrient intake of students participating in the school snack program were compared with students who chose not to participate. Five additional questions asked students about their participation, preferences, and impressions of the snack program. Data sources for the greenhouse project included semi-directed interviews with a purposive and snowball sample of community key informants, direct observations, written documentation, and photo-documentation. The case study was carried out over a period of 33 months; from early 2009 until October of 2011. The supplemental questions for the HFSSM were drafted based on themes that had emerged from the evaluation of the relevance of the HFSSM and relevant literature. Feedback on the importance, clarity, and cultural appropriateness of each proposed question was gathered from key informants (n=12) working on food security issues with Aboriginal groups, using an online survey. Results: For the HFSSM study, of 64 households (87% response), 70% were food insecure, 17% severely and 53% moderately. The prevalence of food insecurity in households with children was 76%. Among respondents from homes rated as having severe food insecurity, all (100%) reported worrying that food would run out; times when food didn’t last and there wasn’t money to buy more; and times when they couldn’t afford to eat balanced meals. When asked about the relevance of the HFSSM, the majority of respondents felt the HFSSM did not fully capture an accurate picture of food security for their situation. Aspects missing from the HFSSM included the high cost of market food and the incorporation of traditional food practices. For the coping strategies study, a thematic analysis of interviews (n=51) revealed that food sharing, especially with family, was regarded as one of the most significant ways to adapt to food shortages. The majority of participants reported consuming traditional food (wild meats) and suggested that hunting, preserving and storing traditional food has remained very important. However, numerous barriers to traditional food acquisition were mentioned. Other coping strategies included dietary change, rationing and changing food purchasing patterns. In order to improve access to healthy foods, improving income and food affordability, building community capacity and engagement, and community-level initiatives were suggested. Findings from the school snack program study showed that students participating in the snack program had significantly higher intakes from specific food groups and related nutrients compared to those who did not participate. With the exception of Meat and Alternatives in 2004, there was a trend for a higher percentage of students to meet dietary recommendations if they participated in the snack program. Students indicated that the three things they liked most about the school snack program were the juice, that the program kept them from feeling hungry at school, and that they got a snack at school every day. Students indicated that the snack program helped them to eat healthier by motivating them, eating more fruit, and making better dietary choices. Qualitative analysis of the greenhouse case study data generated gardening related themes: seasons, fertile ground, sustainability, gardeners, ownership, participant growth, and sunshine. Amongst the gardeners, local champions were critical to project success. Positive outcomes included the involvement of many community members, a host of related activities being carried out, and that the greenhouse had introduced an opportunity to gain knowledge about growing plants in a northern greenhouse setting. For the study on measuring food security in FN households, valuable feedback was provided by key informants (n=12) on clarifying the wording of the questions as well as providing perspectives on how the questions may or may not be applicable to different Aboriginal populations. A revised list of questions was created that incorporated the feedback from key informants. Conclusions: A very high prevalence of household food insecurity was reported in this community with the prevalence especially high in households with children. On-reserve remote FN communities may be more susceptible to food insecurity than off-reserve Aboriginal populations. Findings point to the continued importance of traditional food acquisition and food sharing, as well as community solutions for food systems change. These data highlight that traditional and store-bought food are both part of the strategies and solutions participants suggested for coping with food insecurity. Given the positive impact of the school snack program on the food and nutrient intake of student participants, it is clear that school snack programs can be an important venue to address the nutritional vulnerability of FN youth living in remote communities. Community and school greenhouse projects require local champions to be successful and foster community participation and ownership. Implementing a greenhouse project can engage community members, including children, and provide a great learning opportunity for gardeners in a remote, northern community. Finally, input from community participants and experts suggest additional questions that may add relevance to food security questionnaires for FN populations. Data highlight the urgency for public health policies and initiatives that promote food security for vulnerable FN populations. Findings can be used to inform assessment and program planning activities and to advocate for policies at the local, provincial and federal levels to strengthen community food security

The eigenvalues of isolated bridges with transverse restrains at the end abutments

This paper examines the eigenvalues of multi-span seismically isolated bridges in which the transverse displacement of the deck at the end-abutments is restricted. With this constraint the deck is fully isolated along the longitudinal direction, while along the transverse direction the deck is a simple supported beam at the end abutments which enjoys concentrated restoring forces from the isolation bearings at the center piers. For moderate long bridges the first natural period of the bridge is the first longitudinal period, while the first transverse period is the second period, given that the flexural rigidity of the deck along the transverse direction shortens the isolation period offered by the bearings in that direction. This paper shows that for isolated bridges longer than a certain critical length, the first transverse period becomes longer than the first longitudinal period despite the presence of the flexural rigidity of the deck. This critical length depends on whether the bridge is isolated on elastomeric bearings or on spherical sliding bearings. This result is also predicted with established commercially available numerical codes only when several additional nodes are added along the beam elements which are modeling the deck in-between the bridge piers. On the other hand this result can not be captured with the limiting idealization of a beam on continuous distributed springs (beam on Wrinkler foundation) –a finding that has practical significance in design and system identification studies. Finally, the paper shows that the normalized transverse eigenperiods of any finite-span deck are self-similar solutions that can be represented by a single master curve and are independent of the longitudinal isolation period or on whether the deck is supported on elastomeric or spherical sliding bearings

Greener through gender: what climate mainstreaming can learn from gender mainstreaming

Addressing the urgent global climate crisis demands a rapid and meaningful expansion of “climate mainstreaming,” which refers to the integration of climate objectives in all aspects of development programs and policies. However, progress remains slow and uneven due to bottlenecks in policy and institutional change. Considering the parallel struggle recorded over decades to mainstream gender across the same policy arenas, a key question emerges: what can climate mainstreaming learn from gender mainstreaming? To answer this question, we review 57 policy, strategy, and guidance documents of United Nations agencies, all of which integrate these themes into food security and broader development programming. Our analysis identifies gaps in climate mainstreaming efforts and derives lessons from gender mainstreaming to bridge these gaps. It underscores the importance of adapting programmatic mainstreaming strategies in response to evolving contexts, for example, by simultaneously considering both mainstreaming and targeted interventions. Additionally, it highlights the need to adopt organizational climate mainstreaming and establish mechanisms for accountability. Finally, it emphasizes the urgency of embracing a climate justice lens; in practice, this involves prioritizing populations at greater risk of climate change impacts and actively engaging diverse perspectives in decision-making, particularly communities facing multiple forms of discrimination

Supporting Your Narrative

Moving an idea into a research project can be a daunting task and the early stages of a project set the stage for success. This poster provides tips for novice and expert researchers to start strong. Poster topics help the researcher develop an idea with background reading, form an idea into a well-built research question, translate that question into a search strategy, determine the best tools for a literature search, employ advanced search techniques to locate the most relevant information, identify an appropriate journal in which to publish, and format the manuscript. Librarians from the University of North Dakota\u27s School of Medicine and Health Sciences promote awareness and effective searching of high quality information sources and offer these tips as well as their assistance to researchers at all levels

Enacting genetic responsibility: experiences of mothers who carry the fragile X gene: Experiences of mothers who carry the fragile X gene

A woman who carries the gene for fragile X syndrome (FXS) has a 50 per cent chance per pregnancy of passing the gene to her sons and daughters. In this paper we analyse interview data from mothers who are carriers of the FX gene, and who have at least one child with FXS, to examine how their understandings and enactments of reproductive options, obligations, and responsibilities support an expanded notion of genetic responsibility. Accounts of 108 women from across the United States show that the majority of mothers chose not to have another biological child once they learned their carrier status. They discussed genetic responsibility and reproductive agency in terms of an obligation not to risk having another child who carried the gene, although their accounts reflected the tensions that arose from managing oneself as a genetically at-risk actor. Another 22 mothers either purposefully became pregnant or continued an unplanned pregnancy after finding out their carrier status. These mothers' accounts reflect an expanded version of genetic responsibility that incorporates ideas and values beyond managing risk in what it means to act responsibly in light of genetic knowledge

A novel counterbalanced implementation study design : methodological description and application to implementation research

Background: Implementation research is increasingly being recognised for optimising the outcomes of clinical practice. Frequently, the benefits of new evidence are not implemented due to the difficulties applying traditional research methodologies to implementation settings. Randomised controlled trials are not always practical for the implementation phase of knowledge transfer, as differences between individual and organisational readiness for change combined with small sample sizes can lead to imbalances in factors that impede or facilitate change between intervention and control groups. Within-cluster repeated measure designs could control for variance between intervention and control groups by allowing the same clusters to receive a sequence of conditions. Although in implementation settings, they can contaminate the intervention and control groups after the initial exposure to interventions. We propose the novel application of counterbalanced design to implementation research where repeated measures are employed through crossover, but contamination is averted by counterbalancing different health contexts in which to test the implementation strategy. Methods: In a counterbalanced implementation study, the implementation strategy (independent variable) has two or more levels evaluated across an equivalent number of health contexts (e.g. community-acquired pneumonia and nutrition for critically ill patients) using the same outcome (dependent variable). This design limits each cluster to one distinct strategy related to one specific context, and therefore does not overburden any cluster to more than one focussed implementation strategy for a particular outcome, and provides a ready-made control comparison, holding fixed. The different levels of the independent variable can be delivered concurrently because each level uses a different health context within each cluster to avoid the effect of treatment contamination from exposure to the intervention or control condition. Results: An example application of the counterbalanced implementation design is presented in a hypothetical study to demonstrate the comparison of 'video-based' and 'written-based' evidence summary research implementation strategies for changing clinical practice in community-acquired pneumonia and nutrition in critically ill patient health contexts. Conclusion: A counterbalanced implementation study design provides a promising model for concurrently investigating the success of research implementation strategies across multiple health context areas such as community-acquired pneumonia and nutrition for critically ill patients. © 2019 The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Jennifer Martin" is provided in this record*

Negotiating desires and options: How mothers who carry the fragile X gene experience reproductive decisions

This paper contributes an empirically-based analysis of how women negotiate reproductive desires and constructions of risk in light of genetic information for a single gene disorder with known inheritance patterns. Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and female carriers have a 50% probability with each pregnancy of transmitting the FX gene. We present data from interviews conducted with 108 mothers across the U.S. who participated in a longitudinal, mixed methods study on family adaptations to FXS and who have at least one child with FXS. Women’s accounts of their reproductive desires, actions, and reasoning indicate that the known 50% risk of transmitting the FX gene was a powerful deterrent to attempting to have more children through unmediated pregnancy. The majority (77%) decided not to have any more biological children after carrier diagnosis. This decision often required revising previous plans for how many children they would have, how and when they would have them, and what kind of mothers they would be. However, genetic risk was not a primary consideration in the reproductive calculations of 22 women who chose to continue planned and unplanned unmediated pregnancies. Though women’s reproductive negotiations are constrained by medical discourse and practices, they are also unpredictable and emerge out of lived experiences and sometimes ambivalent ways of reckoning. While increased availability and accuracy of genetic information and testing contribute to certain forms of family planning that prioritize genetic risk management, we also find that some families call upon alternative understandings and desires for making a family to articulate genetic risk and negotiate their reproductive futures

Draft Genome Sequence of Rhodococcus sp. Strain ATCC 49988, a Quinoline-Degrading Bacterium.

We report here the 4.9-Mb genome sequence of a quinoline-degrading bacterium, Rhodococcus sp. strain ATCC 49988. The draft genome data will enable the identification of genes and future genetic modification to enhance traits relevant to heteroaromatic compound degradation