MTG-Link: leveraging barcode information from linked-reads to assemble specific loci.

BACKGROUND: Local assembly with short and long reads has proven to be very useful in many applications: reconstruction of the sequence of a locus of interest, gap-filling in draft assemblies, as well as alternative allele reconstruction of large Structural Variants. Whereas linked-read technologies have a great potential to assemble specific loci as they provide long-range information while maintaining the power and accuracy of short-read sequencing, there is a lack of local assembly tools for linked-read data. RESULTS: We present MTG-Link, a novel local assembly tool dedicated to linked-reads. The originality of the method lies in its read subsampling step which takes advantage of the barcode information contained in linked-reads mapped in flanking regions. We validated our approach on several datasets from different linked-read technologies. We show that MTG-Link is able to assemble successfully large sequences, up to dozens of Kb. We also demonstrate that the read subsampling step of MTG-Link considerably improves the local assembly of specific loci compared to other existing short-read local assembly tools. Furthermore, MTG-Link was able to fully characterize large insertion variants and deletion breakpoints in a human genome and to reconstruct dark regions in clinically-relevant human genes. It also improved the contiguity of a 1.3 Mb locus of biological interest in several individual genomes of the mimetic butterfly Heliconius numata. CONCLUSIONS: MTG-Link is an efficient local assembly tool designed for different linked-read sequencing technologies. MTG-Link source code is available at https://github.com/anne-gcd/MTG-Link and as a Bioconda package.

Nurses' Perceptions of Climate Change: Protocol for a Scoping Review.

BACKGROUND: Climate change is a major threat to human health. Nurses are in contact with patients suffering from the effects of climate change in their daily work. Therefore, they need to be involved in combating it at both the individual and collective levels. However, there is still very little known about nurses' perception of climate change and their role toward it. A few recent studies have embarked on the process of examining the perceptions of these health professionals relative to climate change, but no exploratory review of the literature has been conducted on nurses' perception of this phenomenon. OBJECTIVE: The purpose of this protocol is to develop a research strategy for an exploratory review of the literature focused on identifying nurses' perceptions of climate change. METHODS: Firstly, with the help of a specialized librarian, we defined keywords and their combinations, using an iterative process, to develop a documentary search strategy. This strategy was tested in the following four bibliographic databases: MEDLINE (PubMed), CINAHL, Embase, and Web of Science. A search of the grey literature will also be conducted to supplement the results of the bibliographic database search. The next step will be for 2 members of the research team to carry out a 2-stage selection process using the web-based systematic review software Covidence. They will carry out this selection process independently, with the aim of identifying relevant studies that meet the inclusion criteria for our exploratory review. Finally, data on year of publication, authors, geographic area, article type, study objectives, methodology, and key findings will be extracted from selected articles for analysis. The data will be analyzed by the research team based on an in-depth examination of the findings and will be directed toward answering the research question and fulfilling the study's objective. RESULTS: The results will help in defining nurses' perceptions of climate change more clearly as well as the role they can play and what they need to be able to bring forward solutions to this phenomenon. The findings should also serve to guide the health sector and nursing faculty's interventions aimed at preparing health professionals to act on the potential threats associated with climate change. CONCLUSIONS: The preliminary search suggests a possible gap between the importance of the nursing role in addressing the health impacts of climate change and the nurses' lack of knowledge and awareness on this matter. The results will allow for raising nurses' awareness of their role in the fight against climate change and the ways to address its health effects. This study will also open up new research perspectives on how to equip nurses to better integrate response to climate change issues into their professional practice. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42516.

Pulmonate slug evolution is reflected in the de novo genome of Arion vulgaris Moquin-Tandon, 1855.

Stylommatophoran pulmonate land slugs and snails successfully completed the water-to-land transition from an aquatic ancestor and flourished on land. Of the 30,000 estimated species, very few genomes have so far been published. Here, we assembled and characterized a chromosome-level genome of the "Spanish" slug, Arion vulgaris Moquin-Tandon, 1855, a notorious pest land slug in Europe. Using this reference genome, we conclude that a whole-genome duplication event occurred approximately 93-109 Mya at the base of Stylommatophora and might have promoted land invasion and adaptive radiation. Comparative genomic analyses reveal that genes related to the development of kidney, blood vessels, muscle, and nervous systems had expanded in the last common ancestor of land pulmonates, likely an evolutionary response to the terrestrial challenges of gravity and water loss. Analyses of A. vulgaris gene families and positively selected genes show the slug has evolved a stronger ability to counteract the greater threats of external damage, radiation, and water loss lacking a protective shell. Furthermore, a recent burst of long interspersed elements in the genome of A. vulgaris might affect gene regulation and contribute to rapid phenotype changes in A. vulgaris, which might be conducive to its rapid adaptation and invasiveness.

Complete Annotated Genome Sequence of the Salmonella enterica Serovar Typhimurium LT7 Strain STK003, Historically Used in Gene Transfer Studies.

The genome of Salmonella enterica serovar Typhimurium LT7 comprises a chromosome and two plasmids. One plasmid is very close to pSLT of Salmonella Typhimurium LT2; the second harbors a shufflon region. Prophage content is distinct: LT7 lacks Fels-1, while Gifsy-1 and Fels-2 show island-like divergence and likely programmed inversion, respectively.

Improving Understanding of Reflexivity in Family Medicine: Development of an Educational Tool Based on a Rapid Review.

This article was migrated. The article was marked as recommended. Background: In the last decade, reflexivity has emerged as a key concept in family medicine, as evidenced by its increasing integration in competency statements and frameworks in the field. However, the concept of reflexivity is inconsistent and ill-defined in medical education literature, with variable purposes and associated processes, which is an important barrier to learning and implementing reflective practices. This project built on the results of a rapid review to develop an educational tool supporting the learning and teaching of reflexivity in family medicine. Methods: We conducted a rapid review of quantitative, qualitative and mixed studies relating to reflexivity in family medicine between May 2007 to May 2017 in PubMed, Embase, PsychInfo, CINHAL, ERIC and Education Source. Two reviewers independently identified, selected and reviewed studies. Results of the review were used to frame the content of the tool. Results: Our research strategy initially identified 810 studies, from which 65 studies were retained for analysis. The different conceptions of reflexivity encountered in the included studies were analyzed using thematic analysis. Four conceptions of reflexivity (i.e. clinical, professional, relational and social reflexivity), with related definitions, goals and processes were identified in the included studies and were used as a basis to develop the Reflexivi-Tool. Conclusion: There is a need to provide clear guidelines regarding the purpose and process of reflexivity, as well as better equipping mentors so they can better facilitate these kinds of skills. Based on a rapid review, this study has allowed the development of a tool that presents and clarifies four main types of reflexivity for medical practice in a concise and user-friendly way. Tools such as Reflexivi-Tool are crucial to support reflective processes that target different dimensions of professionalism.

Developing the culture of ethics in population health intervention research in Canada.

Population health intervention research (PHIR) is a particular field of health research that aims to generate knowledge that contributes to the sustainable improvement of population health by enabling the implementation of cross-sectoral solutions adapted to social realities. Despite the ethical issues that necessarily raise its social agenda, the ethics of PHIR is still not very formalized. Unresolved ethical challenges may limit its focus on health equity. This contribution aims to highlight some of these issues and calls on researchers to develop a culture of ethics in PHIR. Three complementary ways are proposed: to build an ethical concept specific to this field, to promote a shared space for critical reflection on PHIR ethics, and to develop the ethical competence in PHIR for which a preliminary framework is proposed.

Equity at all cost-and any price-for research funding in Canada?

This commentary is in response to the May 2018 announcement by the Canadian Institutes of Health Research (CIHR) of a new procedure to ensure fairer access to health research funding for participants. As such, all applicants to CIHR's funding programs will now be required to complete a five-question questionnaire covering the dimensions of gender, age, Indigenous origin, visible minorities, and disability. On this basis, CIHR intends to gain a better understanding of the performance of its funding programs in terms of equity. In this commentary, we wish to question the theoretical and conceptual assumptions of a vision of equity framed principally in terms of diversity upstream from the research process as a founding principle of more equitable health research in Canada. We draw attention to the fact that diversity policies do not necessarily challenge inequity in research funding or in research projects. Having established the urgent need for action on equity to improve the health of populations, we recall the ethical responsibility of research and researchers to better take the various facets of equity in research into account. We recommend expanding efforts to understand and reflexively address both equity and diversity when considering the performance of population health research programs.

[Adaptation and conditions of use of a health equity tool: The Reflex-ISS tool]. / Adaptation et conditions d'utilisation d'un outil d'analyse des interventions au regard des inégalités sociales de santé.

Although actions to reduce social inequalities in health cannot be considered the exclusive responsibility of public health actors, they should at least make sure their interventions account for these inequalities. However, the actors involved in these interventions have few tools to support them in this process. Therefore, building on a study conducted in France, we have adapted, tested, and developed in Quebec a tool intended to help actors take into account social inequalities in health. The article presents the approach that led to the adaptation of the tool to the Quebec context, to describe the tool, and then to discuss some issues for inclusion in professional practices. A participatory and constructive process between researchers, managers and practitioners led to a useful and useable tool. It is composed of five aspects of intervention (planning, implementation, evaluation, sustainability, and empowerment) and 44 items for discussion presented as questions. A user guide, a glossary, and some practical examples accompany the tool. It follows a reflexive and constructive process wherein a third party facilitator can assist actors involved in an intervention to analyze how they take social inequalities in health into account. This assessment can help generate collective recommendations for improvements, which can be monitored over time, to improve consideration of equity in public health interventions. The article concludes on some issues related to its integration into professional practices.

1H, 13C, 15N NMR resonance assignments and secondary structure determination of the extra-cellular domain from the human proapoptotic TRAIL-R2 death receptor 5 (DR5-ECD).

Death receptors (DR) selectively drive cancer cells to apoptosis upon binding to the Tumor necrosis factor-a-Related Apoptosis-Inducing Ligand (TRAIL). Complex formation induces the oligomerization of the death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) and transduces the apoptogenic signal to their respective death domains, leading to Death Inducing Signaling Complex (DISC) formation, caspase activation and ultimately cell death. Several crystal structures of the ExtraCellular Domain from Death Receptor 5 (DR5-ECD) have been reported in complex with the TRAIL ligand or anti-DR5 antibodies, but none for the isolated protein. In order to fill this gap and to perform binding experiments with TRAIL peptidomimetics, we have produced isotopically labelled DR5-ECD and started a conformational analysis by using high-field 3D NMR spectroscopy. Herein, we present the first resonance assignment of a TRAIL receptor in solution and the determination of its secondary structure from NMR chemical shifts.

[Social inequalities in health, challenges for nursing care]. / Les inégalités sociales de santé, enjeux pour les soins infirmiers.

The main factors of social inequalities in health lie outside the healthcare system. In a context centred on curative care, the influence of social determinants on people's health is a challenge facing nursing care and highlights the need to reinforce cross-sector action.

Use of concurrent mixed methods combining concept mapping and focus groups to adapt a health equity tool in Canada.

The aim of this project was to identify and prioritize a set of conditions to be considered for incorporating a health equity tool into public health practice. Concept mapping and focus groups were implemented as complementary methods to investigate the conditions of use of a health equity tool by public health organizations in Quebec. Using a hybrid integrated research design is a richer way to address the complexity of questions emerging from intervention and planning settings. This approach provides a deeper, operational, and contextualized understanding of research results involving different professional and organizational cultures, and thereby supports the decision-making process. Concept mapping served to identify and prioritize in a limited timeframe the conditions to be considered for incorporation into a health equity tool into public health practices. Focus groups then provided a more refined understanding of the barriers, issues, and facilitating factors surrounding the tools adoption, helped distinguish among participants' perspectives based on functional roles and organizational contexts, and clarified some apparently contradictory results from the concept map. The combined use of these two techniques brought the strengths of each approach to bear, thereby overcoming some of the respective limitations of concept mapping and focus groups. This design is appropriate for investigating targets with multiple levels of complexity.

Professional development programs in health promotion: tools and processes to favor new practices.

Developing innovative interventions that are in sync with a health promotion paradigm often represents a challenge for professionals working in local public health organizations. Thus, it is critical to have both professional development programs that favor new practices and tools to examine these practices. In this case study, we analyze the health promotion approach used in a pilot intervention addressing children's vulnerability that was developed and carried out by participants enrolled in a public health professional development program. More specifically, we use a modified version of Guichard and Ridde's (Une grille d'analyse des actions pour lutter contre les inégalités sociales de santé. In Potvin, L., Moquet, M.-J. and Jones, C. M. (eds), Réduire les Inégalités Sociales en Santé. INPES, Saint-Denis Cedex, pp. 297-312, 2010) analytical grid to assess deductively the program participants' use of health promotion practices in the analysis and planning, implementation, evaluation, sustainability and empowerment phases of the pilot intervention. We also seek evidence of practices involving (empowerment, participation, equity, holism, an ecological approach, intersectorality and sustainability) in the intervention. The results are mixed: our findings reveal evidence of the application of several dimensions of health promotion (equity, holism, an ecological approach, intersectorality and sustainability), but also a lack of integration of two key dimensions; that is, empowerment and participation, during various phases of the pilot intervention. These results show that the professional development program is associated with the adoption of a pilot intervention integrating multiple but not all dimensions of health promotion. We make recommendations to facilitate a more complete integration. This research also shows that the Guichard and Ridde grid proves to be a thorough instrument to document the practices of participants.

The concept of mechanism from a realist approach: a scoping review to facilitate its operationalization in public health program evaluation.

BACKGROUND: Public health interventions are complex by nature, and their evaluation requires unpacking their intervention logic and their interactions with open social systems. By focusing on the interrelationships between context, mechanism, and outcome, Pawson and Tilley's realist approach appears a promising innovation for public health-related evaluation works. However, and as expected of any methodological innovation, this approach is being constructed gradually by answering the multiple challenges to its operationalization that fall in its path. One of these challenges, users of this approach agree on, is the necessity of clarifying its key concept of mechanism. METHOD: We first collected the definitions of mechanism from published works of Pawson and colleagues. Secondly, a scoping review was conducted to identify the ones quoted by users of the realist approach for evaluating public health interventions (1997-2012). We then appraised the clarity and precision of this concept against the three dimensions defined by Daigneault and Jacobs "term, sense and referent." RESULTS: Of the 2344 documents identified in the scoping review, 49 documents were included. Term: Users of the realist approach use adjectives qualifying the term mechanism that were not specifically endorsed by Pawson and colleagues. Sense: None of the attributes stated by Pawson and colleagues has been listed in all of the documents analyzed, and some contributions clarified its attributes. Referent: The concept of mechanism within a realist approach can be ascribed to theory-based evaluation, complex social interventions, and critical realism. CONCLUSION: This review led us to reconsider the concept of mechanism within the realist approach by confronting the theoretical stance of its proponents to the practical one of its users. This resulted in a clearer, more precise definition of the concept of mechanism which may in turn trigger further improvements in the way the realist approach is applied in evaluative practice in public health and potentially beyond. A mechanism is hidden but real, is an element of reasoning and reactions of agents in regard to the resources available in a given context to bring about changes through the implementation of an intervention, and evolves within an open space-time and social system of relationships.

Risk Factors Associated with Unsafe Injection Practices at the First Injection Episode among Intravenous Drug Users in France: Results from PrimInject, an Internet Survey.

UNLABELLED: Background. New drug use patterns may increase the risk of human immunodeficiency virus and hepatitis infections. In France, new injection patterns among youths with diverse social backgrounds have emerged, which may explain the persistently high rates of hepatitis C virus infection. This study explores factors associated with injection risk behaviours at first injection among users who began injecting in the post-2000 era. Methods. A cross-sectional study was conducted on the Internet from October 2010 to March 2011, through an online questionnaire. Multivariate logistic regression identified the independent correlates of needle sharing and equipment (cooker/cotton filter) sharing. Results. Among the 262 respondents (mean age 25 years), 65% were male. Both risk behaviours were positively associated with initiation before 18 years of age (aOR 3.7 CI 95% 1.3-10.6 and aOR 3.0 CI 95% 1.3-7.0) and being injected by another person (aOR 3.1 CI 95% 1.0-9.9 and aOR 3.0 CI 95% 1.3-7.1). Initiation at a party was an independent correlate of equipment sharing (aOR 2.6 95% CI 1.0-6.8). CONCLUSIONS: Results suggest a need for innovative harm reduction programmes targeting a variety of settings and populations, including youths and diverse party scenes. Education of current injectors to protect both themselves and those they might initiate into injection is critically important.

Scaling-up the use of generic antiretrovirals in resource-limited countries: generic drugs for health.

The number of people living with HIV (PLHIV) continues to increase around the world because of the increasing number on antiretroviral therapy (ART) and their associated increase of life expectancy, in addition to the number of people newly infected with HIV each year. Unless a 'cure' can be found for HIV infection, PLHIV can anticipate the need to take antiretroviral drugs (ARVs) for the rest of their lives. Because ARVs are now being used for HIV prevention, as well as for therapeutic purposes, the need for effective, affordable ARVs with few adverse effects will continue to rise. It is important to note that the dramatic growth in treatment coverage of PLHIV seen during the past decade has been primarily due to the increased use of generic ARVs. Thus, there will be a need to scale-up the research and development, production, distribution and access to generic ARVs and ART regimens. However, these processes must occur within national and international regulated free-market economic systems and must deal with increasingly multifaceted patent issues affecting the price while ensuring the quality of the ARVs. National and international regulatory mechanisms will have to evolve, which will affect broader national and international economic and trade issues. Because of the complexity of these issues, the Editors of this Supplement conceived of asking experts in their fields to describe the various steps from relevant research and development, to production of generic ARVs, their delivery to countries and subsequently to PLHIV in low- and middle-income countries. A main objective was to highlight how these steps are interrelated, how the production and delivery of these drugs to PLHIV in resource-limited countries can be made more effective and efficient, and what the lessons are for the production and delivery of a broader set of drugs to people in low- and middle-income countries.

Changing patterns of first injection across key periods of the French Harm Reduction Policy: PrimInject, a cross sectional analysis.

BACKGROUND: Monitoring of emerging modes of drug consumption in France has identified new patterns of injection among youths with diverse social backgrounds, which may explain the persistence of high rates of hepatitis C virus infection. The circumstances surrounding the first injection have been poorly documented in the group of heavy drug users and in the context of the French opioid substitution treatment (OST) policy that provides expanded access to high-dosage buprenorphine (BHD) METHODS: An Internet survey (Priminject) was conducted from October 2010 to March 2011 with French drug users. Four time periods were compared based on critical dates throughout the implementation of the Harm Reduction Policy in France. RESULTS: Compared with drug users who injected for the first time prior to 1995, the aspects of drug use for users who recently injected for the first time were as follows: (1) experimentation with miscellaneous drugs before the first injection; (2) an older age at the time of first injection; (3) heroin as the drug of choice for an individual's first injection, notwithstanding the increased usage of stimulant drugs; (4) BHD did not appear to be a pathway to injection; and (5) an increased number of users who injected their first time alone, without the help or presence of another individual. CONCLUSION: The PrimInject study showed that there is a group of injection drug users that is larger than the group of injection drug users observed in previous studies; therefore, it is necessary to diversify programs to reach the entire spectrum of high-risk users.

Social inequalities in health from Ottawa to Vancouver: action for fair equality of opportunity.

The authors set out to show that the Ottawa Charter of 1986 has not been sufficiently accepted over the past twenty years, even by those who use it as a strategic tool to guide interventions for reducing social inequalities in health. Although some public health policies do emphasize the reduction of social inequalities in health, only the Ottawa Charter appears to possess the status of an international declaration on the matter. Social inequalities in health are the systematic, avoidable, and unjust differences in health that persist between individuals and sub-groups of a population. Four examples from the field of health promotion serve to show that forgetting to combat social inequalities in health is not exclusive to the domain of public health. However, taking action against social inequalities in health does not equal tackling poverty. Moreover, intervening on the principle of equality of opportunity, on the basis of an ideology of meritocracy, or for the benefit of the population as a whole, without regard to sub-groups, only tends, at best, to reproduce inequalities. Although evidence is insufficient, there are studies that show that reducing social inequalities in health is not an aporia. Three explanations are advanced as to why social inequalities in health have been ignored by health promotion professionals. The Ottawa Charter had the merit of highlighting the struggle against social inequalities in health. Now, moving beyond the declarations, from the strategic framework provided by the Ottawa Charter and in accordance with the Bangkok Charter, it is time to show proof of voluntarism. Several priorities for the future are suggested and the International Union for Health Promotion and Education (IUHPE) should be responsible for advocating for them.

Buprenorphine substitution treatment in France: drug users' views of the doctor-user relationship.

The French system for drug substitution, or maintenance treatment, established in 1996, differs from the often strict conditions attached to methadone clinics in other countries. Because of the predominant role of general practitioners and the flexible prescription rules for Subutex in France, the relationship between the physician and the drug user becomes a central element in the treatment. This article deals with the expectations that these users have of the physician, and their perception of his or her attitude towards them. In order to identify possible reasons for the absence of treatment compliance and of Subutex misuse, it focuses on the users' assessment of the physician's response to the problems they report. This study, based on a diversified convenience sample of 28 persons (19 men, 9 women) in treatment, showed 4 patterns of relationships between physicians and users, which differed in their focus: (1) closely focused on the posology of the prescription; (2) compliance with the prescribed regimen is the main issue in a relationship dominated by the physician; (3) an alliance between the physician and the user who is acknowledged as a person, and (4) a instrumental solely on the part of the user, who comes to procure a free, legal drug from a doctor's office. In all four case types, users had difficulty reporting other drug use or intravenous Subutex injection within this relationship, in which the stigma attached to drug dependence seems to reappear. Moreover, the lack of clarity about the treatment objectives and the time frame of the consultation limits the users' ability to integrate the treatment into their lives and to commit themselves to it. The heterogeneity and fragility of the users' situations, and the treatment objectives require regular assessment during contact with the physician. This constant reappraisal of the situation with the physician should help to optimize the treatment and avoid the hiatus that can generate or continue "misuse."

Social inequalities in health from Ottawa to Vancouver: action for fair equality of opportunity

Los autores pretenden demostrar que, en estos 20 últimos años, la Carta de Ottawa de 1986 no ha sido percibida, ni siquiera por los que refieren a ella, como un instrumento estratégico orientador de las intervenciones a favor de la redución de las desigualdades sociales en el ámbito de la salud. Efectivamente, si bien determinadas políticas públicas sanitarias hacen hincapié en la disminución de las desigualdades sociales de salud, parece que únicamente la Carta de Ottawa disponga de la categoría de declaración internacional a tal efecto. Las desigualdades sociales de salud son las diferencias de salud sistemáticas, evitables e injustas que perduran entre las personas y los subgrupos de población. Cuatro ejemplos pertenecientes al campo de la promoción de la salud sirven para demostrar que el olvido de luchar contra dichas desigualdades no es propio dos que dicen pertenecer a la salud pública. Pero actuar contra las desigualdades sociales de salud no es intervenir contra la pobreza. Es más, actuar en base al principio de la igualdad de oportunidades, la ideología de la meritocracia o únicamente al favor del conjunto de la población, sin preocuparse de los subgrupos, sólo desemboca, en el mejor de los casos, en la reproducción de las desigualdades. Aunque no contamos con suficientes datos concluyentes, existen estudios que muestran que la reducción de las desigualdades sociales en el ámbito de la salud no es una aporía. Avanzamos tres pistas para explicar este olvido de las desigualdades sociales de salud por parte de los actores de la promoción de la salud. La Carta de Ottawa tuvo el mérito de hacer hincapié en la lucha contra dichas desigualdades. Ahora, más allá de las declaraciones, del marco estratégico que la Carta ofrece y de acuerdo con la Carta de Bangkok, tenemos que demostrar nuestra voluntad. Apuntamos algunas prioridades de futuro, cuya defensa debería asumir la UIPES.(AU)