Biodiversity loss and climate change are both globally significant issues that must be addressed through collaboration across countries and disciplines. With the December 2015 COP21 climate conference in Paris and the recent creation of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES), it has become critical to evaluate the capacity for global research networks to develop at the interface between biodiversity and climate change. In the context of the European Union (EU) strategy to stand as a world leader in tackling global challenges, the European Commission has promoted ties between the EU and Latin America and the Caribbean (LAC) in science, technology and innovation. However, it is not clear how these significant interactions impact scientific cooperation at the interface of biodiversity and climate change. We looked at research collaborations between two major regions—the European Research Area (ERA) and LAC—that addressed both biodiversity and climate change. We analysed the temporal evolution of these collaborations, whether they were led by ERA or LAC teams, and which research domains they covered. We surveyed publications listed on the Web of Science that were authored by researchers from both the ERA and LAC and that were published between 2003 and 2013. We also run similar analyses on other topics and other continents to provide baseline comparisons. Our results revealed a steady increase in scientific co-authorships between ERA and LAC countries as a result of the increasingly complex web of relationships that has been weaved among scientists from the two regions. The ERA-LAC co-authorship increase for biodiversity and climate change was higher than those reported for other topics and for collaboration with other continents. We also found strong differences in international collaboration patterns within the LAC: co-publications were fewest from researchers in low- and lower-middle-income countries and most prevalent from researchers in emerging countries like Mexico and Brazil. Overall, interdisciplinary publications represented 25.8% of all publications at the interface of biodiversity and climate change in the ERA-LAC network. Further scientific collaborations should be promoted 1) to prevent less developed countries from being isolated from the global cooperation network, 2) to ensure that scientists from these countries are trained to lead visible and recognized biodiversity and climate change research, and 3) to develop common study models that better integrate multiple scientific disciplines and better support decision-making. There is an increasing need to address global issues like biodiversity loss and climate change . Howeverwww.eeas.europa.eu/lac; see [http://www.claris-eu.org/) brought 9 partners from LAC and 11 from EU together, to build possible scenarios on climate change on La Plata Basin and design adaptation strategies. The main areas of common interest promoted by the FP7 were renewable energies, climate services, bio-economy, marine research, ICT and health. Following the adoption by the EU-LAC Madrid Summit of the Joint Initiative for Research and Innovation (JIRI) in 2010, the EC has intensified its support for policy dialogue on science and technology. In particular, this led to the launch of the ALCUE-Net project  with the main objective to establish a bi-regional platform between actors involved in research and innovation, relevant stakeholders from the public and private sectors, and civil society so that a long-standing EU-LAC dialogue on science and technology could be implemented. The EC also supported the ERANet-LAC (http://eranet-lac.eu), which is a network of the EU and LAC Countries strengthening the bi-regional partnership in science, technology and innovation by planning and implementing concrete joint activities such as joint calls for research projects.Europe is the major donor for research and development cooperation in Latin America and the Caribbean (LAC), is the largest foreign direct investor in LAC, and is a key promoter of regional integration . In the lac; see  for moreBeyond European programmes and initiatives, collaborative research between the ERA and LAC at the interface of biodiversity loss and climate change is also spurred by bilateral schemes that promote research between one European country and one LAC country. For instance, Brazil and Mexico were among the 14 countries for which the French National Research Agency (ANR) dedicated a bilateral scheme in 2014. For several years, the German Research Foundation (DFG) has operated a joint funding program with the Brazilian partner organisations FAPESP in the state of São Paulo and FAPEMIG in the state of Minas Gerais based on bilateral cooperation agreements.However, it is not clear how these European, trans-continental and bilateral research programmes impact scientific cooperation at the interface of biodiversity and climate change. Political leaders in the European Union (EU) and in LAC have long recognised the importance of incorporating scientific knowledge into proposed solutions to the increasingly complex challenges that biodiversity loss and climate change pose to society at both local and global scales , 9. MoreBibliographic analyses are useful for quantifying bi-regional cooperation in scientific research , 15. In Using the Web of Science version of the Thomson Reuters citation databases , we searched the peer-reviewed literature (articles and reviews) published between 2003 and 2013 that focused on biodiversity, climate change and both together, and identified papers originating from ERA and LAC countries. The Web of Science platform draws from several online databases, three of which were particularly relevant for our search: two from the core collection  and one from the Arts & Humanities Citation Index . We found only four additional references by using other databases, including SciELO (mainly for South America), Scopus, Social Science Research Network, BioOne and MUSE.We retrieved all publications with at least one author from a country within LAC  and all publications with at least one author from a country within the ERA . The publications with at least one author from a LAC country and at least one author from an ERA country were considered an ERA-LAC co-publication, as were publications authored by at least one scientist who was affiliated with organizations in both the ERA and LAC. To obtain baseline comparisons, we also performed a search for other continents, i.e. North America, Africa, Asia and Oceania.As biodiversity is a broad, multi-faceted concept, we used the following keyword profile to identify biodiversity-related publications: TOPIC = . To search for publications on climate change, we used the following keywords: TOPIC = . We cross-referenced the two searches to identify publications at the interface of biodiversity and climate change and checked that all articles were related to these two specific topics. To obtain baseline comparisons, we also performed a search for other topics, i.e. all the publications not using any of the above-mentioned keywords.All records were imported into an Excel dynamic database. Each record was tagged with its corresponding WoS section, SCI, SSCI or AHCI, a repeatable attribute as a relatively high level of record duplication exists between the three sections. The database was cleaned to avoid duplications and remove errors and inconsistencies .We used the author addresses listed in the papers to determine the international networks of researchers. For each paper, we recorded information on all authors and identified the collaborating countries. Finally, we computed a triangular matrix to identify the strength of the links between each pair of countries based on the number of papers co-authored by these countries. Co-publication network mapping and analysis were performed using the open source Gephi software  connected by edges (based on co-authorship) according to the following rules: 1) node size represents the number of publications, 2) all nodes are attracted to the center (the country with the highest number of publications), 3) all nodes repel each other , 4) all nodes that are connected by an edge attract each other, according to the weight of the edge (the number of publications with co-authorship between the two countries/regions). Two nodes are thus spatially closer if there are many collaborative publications. To examine the dynamics of the development of ERA-LAC co-authorship networks that were working at the interface of biodiversity and climate change over the last 11 years, we built maps for two different periods: 2003–2008 and 2008–2013.We also created two-dimensional maps of the co-publication networks at the global level, looking at collaborations between the ERA, LAC, other European countries, North America, Africa, Asia, Oceania. As these networks were drawn on a world map background, only node size and edge weight were represented.st denote the number of shortest paths from s to t, where σss = 1 by convention. Let σst (υ) denote the number of shortest paths from s to t that some υ ∈ V lies on. The betweeness centrality CB(υ) of each country can be calculated as  thelated as :CB(υ)=∑i is the number of individuals of the ith author/institution/project in the database. For PIE < 0.70, the lower the PIE value, the more uneven its abundance distribution, i.e. it would be increasingly characterized by the dominance of one or a few authors/institutions/projects [We identified the country of the corresponding authors of all the ERA-LAC publications that study biodiversity and climate change together to see which countries were the main scientific leaders of these publications. To examine whether effects attributed to countries might actually be the work of a small number of prolific individuals, institutions or projects, we measured a diversity index on author, affiliation and funding fields of our database, using the probability of interspecific encounter . PIE exprojects .To assess how involved different scientific communities were in ERA-LAC collaborations on issues related to biodiversity and climate change, we also computed 1) the proportion of ERA-LAC publications at the interface of biodiversity and climate change that correspond to five major scientific disciplines defined by the WoS , 2) several themes in each discipline . Several themes could be attributed to a single publication . For publications classified as ‘biological science’, which made up most of the records, we also identified whether the study was performed in terrestrial, marine or freshwater ecosystems, and whether the study had been performed within an LAC country or within the ERA. Better-resolution ecosystem units  were not included in our analysis as 1) many articles spanned several ecosystem units , 2) several articles concerned systems that were related to several ecosystem units , 3) many studies were conducted in very singular ecosystems occurring only a few times in the database . Therefore, any analysis on ecosystem specificities would have been poorly relevant. In addition, we used a Venn diagram to visualize the interdisciplinarity of the ERA-LAC research on biodiversity and climate change, distinguishing three large disciplinary fields: biological, earth and human sciences.The number of peer-reviewed publications that arose from collaborations between ERA and LAC countries on biodiversity, climate change and at the interface of biodiversity and climate change all increased exponentially between 2003 and 2013 , with thAt a global scale, ERA-LAC co-publications represented 7.9% of the total number of publications at the interface of biodiversity and climate change between 2003 and 2013, co-publications between the ERA and North America representing 22.9%. Between 2003 and 2013, Europeans authored 2.8 times more publications at the interface of biodiversity and climate change than did LAC scientists .Europeans published studies at the interface of biodiversity and climate change mainly through intra-European networks , and to a lesser extent with North America 18.2%; . ERA-LACLAC scientists published studies at the interface of biodiversity and climate change equally with the ERA, North America and other LAC countries (27.0 to 29.2%), and they rarely published with colleagues from Oceania, Asia and Africa . The num2 = 0.44, p < 0.05) and from around 25% to 40% of total LAC publications over the same period . The increase in collaborative ERA-LAC papers at the interface of biodiversity and climate change (4.8 more papers in 2008–2013 than in 2003–2008) over time was associated with an expanded and more complex network of co-author links  increased with the number of publications produced, i.e. countries with fewer publications generally had lower betweenness centrality coefficients . HoweverOverall, ERA researchers were corresponding authors for 50% of the ERA-LAC publications at the interface of biodiversity and climate change, while 30% were LAC researchers . ERA autNo ERA-LAC authors, institutions or projects contributed disproportionally to the bulk of publication . The most prolific authors, institutions and projects accounted to a maximum of 2.0, 3.8 and 3.1% of all publications, respectively).Biological science was by far (63%) the most common theme among the ERA-LAC publications at the interface of biodiversity and climate change, followed by earth sciences (14%), technology sciences (13%) and human sciences (8%) . The mosOverall, 85% of all studies in biological sciences were conducted in sites/organisms within LAC territories, mainly in terrestrial and freshwater environments, and to a lesser extent, marine environments —inset. IWithin the LAC region is an exceptionally rich diversity of species and ecosystems. There is already severe pressure on the capacity of these species and ecosystems to deliver essential services to society , 20, 21.Growth in the number of papers at the interface of biodiversity and climate change has been exponential over the last decade, indicating that scientists in the ERA and LAC have recognized the importance of studying the links between biodiversity and climate change. The proportion of publications at the interface of biodiversity and climate change and of publications involving ERA-LAC partners has also significantly increased between 2008 and 2013 than it did between 2003 and 2008. This increase in ERA-LAC publication in biodiversity and climate change was higher than that for other topics and with other regions of the world, even North America. In addition, although EU development policy aims to support Latin American regional integration , our stuThese two main characteristics of the ERA-LAC collaborations at the interface of biodiversity and climate change, i.e. growth in collaborations and marked differences in representation among countries, have already been reported in other studies on international scientific cooperation, both between ERA-LAC regions  and worlThe increase in scientific co-authorships between ERA-LAC countries is also likely an outcome of the increasingly complex web of relationships that has been weaved between scientists of the two regions . While shttp://alcuenet.eu/meeting-events.php?event=TkRRNA), a major barrier to the scientific cooperation between biodiversity and climate change communities seems to be the discrepancy in the data formats, resolution, uncertainties, and access of each community. To improve understanding and collaboration between both communities, their dialogue should be strengthened through capacity building activities and cooperation projects so that biodiversity community’s expectations could be better identified and climate models limitations better assessed. Moreover, although the internal disciplinary differentiation of science motivates linkages among research teams in specific research domains at the international level [Many issues addressed by the scientific community studying biodiversity and climate change together  requires an interdisciplinary approach that includes life, earth and social sciences. Our study found that about one fourth of all studies on biodiversity and climate change within the ERA-LAC cooperation network were interdisciplinary. These levels may be underestimated, as our publication sample was not selected on terms that might have pulled in more human science papers. Moreover, within the large categories are also many disciplines and important interdisciplinarity which may be overlooked. While our study cannot conclude on the importance of interdisciplinarity in the ERA-LAC network, this issue is central to sound research on biodiversity and climate change and would merit further investigations. As evidenced in a recent ALCUE-Net meeting  are promising advances to address this issue.Over the last twenty years, the ERA and LAC countries have committed themselves to consolidating their links through a strategic partnership. A major objective of these reinforced links is often to build countries’ capacity. However our analysis shows that while most ERA-LAC studies are performed on sites located in LAC territories only one third of the corresponding publications are led by LAC scientists. However, the relationship between capacity building and publication authorship is not straightforward and the poor leadership of LAC scientists may also illustrate the ERA origins of the funding and lack of research coordination in the LAC region. A second major objective is to promote academic excellence and productivity. Further parameters like journal impact factors and corresponding author metrics could be incorporated into bibliometric analyses to assess whether ERA-LAC collaboration has developed in a way that fulfils this goal. A third major objective of reinforced ERA-LAC links is to properly study the interplay of biodiversity and climate change issues over the entire LAC area. However, our results indicate that ERA-LAC collaboration is biased towards a few, emerging countries, with most studies focused on sites in Brazil and Mexico (which is a powerful actor of intra-LAC cooperation), and there is a need to better tailor cooperation with low- and mid-income countries by conducting more targeted collaborations for R&D studies on biodiversity and climate change. However, strengthening the connection between less developed countries and the global cooperation network will not be easy. For example, Bolivia appears in our analysis only as a peripheral link to the global network through regional hubs, but it has very limited academic resources in biodiversity and climate change science. The limitations of climate model downscaling  and theS1 Table(TXT)Click here for additional data file.


Obesity is a major problem in the United States, particularly among socio-economically disadvantaged Latino and Black children. Effective interventions that can be disseminated to large numbers of at-risk children and their families are needed. The goals of the Early Childhood Obesity Prevention Program (ECHO) are to examine the 12-month efficacy of a primary obesity prevention program targeting the first year of life that is delivered by home visitors and that engages mothers as agents of change to modify their own behavior and their infant’s behavior through education and skill-building around nutrition, physical activity, and wellness, and then “echoes” her training with linkages to neighborhood programs and resources.z-score at 12 months, and their mothers will have greater fruit and vegetable consumption and higher levels of physical activity.Six family centers located in low-income neighborhoods in Hartford, CT were randomized into control and intervention neighborhoods. Fifty-seven mothers were recruited either prenatally or shortly after delivery into the Nurturing Families Network home visitation program; 27 lived in a control neighborhood and received the standard home visitation program and 30 lived in an intervention neighborhood and received both the standard home visitation program and the ECHO intervention. The intervention increases maternal skills in goal-setting, stimulus control and problem-solving, engages family members to support changes, links mothers to neighborhood resources and is embedded in the standard home visitation program. ECHO targets include breastfeeding, solids, juice and sugar-sweetened beverages, routines for sleep and responding to infant cues, television/screen time, and maternal diet and physical activity. We hypothesize that infants in ECHO will have been breastfed longer and exclusively, will have delayed introduction of solids and juice, have longer sleep duration, decreased television/screen time and a lower weight for length ECHO will provide important information about whether an enhanced behavior change curriculum integrated into an existing home visitation program, focused on the mother as the agent of change and linked to neighborhood resources is effective in changing energy balance behaviors in the infant and in the mother. If effective, the intervention could be widely disseminated to prevent obesity in young children.NCT02052518 January 30, 2014.ClinicalTrials.gov  The prevalence of obesity in the United States has tripled in the past 40 years  with disParents as Teachers program to increase fruit and vegetable consumption; they demonstrated a reduced weight for length and changes in parental behavior [Many childhood obesity prevention efforts have focused on school-age children . There ibehavior .Thus, parental education and maternal behavior change appear to be important components of obesity prevention. They may not, however, be sufficient to prevent obesity if mothers do not have access to, cannot afford, or don’t know how to prepare quality food and/or don’t feel safe in their community. Ecological models of obesity Fig.  recognizHome visitors can support behavior change effectiveness and can reach high-risk pregnant women and mothers during this early and critical period in a culturally responsive way –16. NatiParents as Teachers-Born to Learn (PAT) and Partners for a Healthy Baby (Partners)) and a culturally diverse workforce [The Nurturing Families Network (NFN) is a nationally recognized, evidence-based home visitation program with credentialed educators, and in Connecticut, is a program of the Children’s Trust Fund. The NFN Home Visitation Program uses two evidence-based curricula /juice consumption, delaying the introduction of solids, limiting television/screen time, establishing infant routines around sleep, and recognizing infant cues to hunger and satiety. Breastfeeding decreases initial weight gain and is one strategy for reducing childhood overweight , althougEarly Childhood Obesity Prevention Program (ECHO): Building Healthier Families and Communities. ECHO is a randomized, controlled trial designed to examine the efficacy at 12 months of a home visitation program that engages mothers as agents of change to modify their own behavior and their infant’s behavior through education and skill building in the areas of nutrition, physical activity, and wellness, and then “echoes” her training with linkages to neighborhood programs . ECHO recruits pregnant women and new mothers who have agreed to participate in NFN’s home visitation program and provides them with an enhanced curriculum that increases maternal skills in goal-setting, problem-solving, and stimulus control to target four specific infant-related behaviors  and follows the mother-infant dyad until the infant is 12 months of age. The program also provides education and linkages to community resources to improve the mother’s health, nutrition and physical activity. The study’s focus on newborns and mothers as agents of change adds to the small literature on obesity prevention in this critical developmental window.Understanding the context in which obesogenic behaviors occur, helping parents of very young children to establish positive behaviors, and linking families to community resources could prevent the development of obesity in young children. These goals are the foundation of an intervention called the Pregnant women or new mothers within one month of delivery who reside in one of six urban neighborhoods in Hartford, CT and were recruited into the NFN program were invited to participate in ECHO. These six neighborhoods were chosen because they are served by a Brighter Future Family (BFF) Center that is linked to the Nurturing Families Network home visitation program. Brighter Future Family Centers provide early childhood education programs and parenting classes designed to improve parents’ knowledge of child development and nurturing skills, support in earning a high school degree, understanding and speaking English, computer use and financial literacy and family play groups. Centers also provide information to parents about other community, city, state and national resources that might help them.The six Brighter Future Family (BFF) Centers in Hartford, Connecticut and their NFN programs were paired by neighborhood socioeconomic and racial/ethnic characteristics Table  and wereth percentile. The study protocol was approved by the Institutional Review Board at Connecticut Children’s Medical Center, was sponsored by the Hartford Childhood Wellness Alliance, and was funded by the National Institutes of Health (NICHD R21 HD073966-A01).We hypothesized that at 6 and 12 months, as compared to NFN infants, NFN+ infants would have been breastfed longer and more often exclusively, would drink less sugar-sweetened beverages/juice, would have begun to ingest solids at an older age, and would sleep more hours/day, have more established sleep/wake routines, greater soothability and have fewer hours of television viewing/day. Secondary hypotheses of the study included that at 6 and 12 months, as compared to NFN families, NFN+ families would purchase, cook and serve more fruits and vegetables, demonstrate greater utilization of BFF Centers and community resources, and NFN+ infants would be less likely to have a weight for length greater than the 85Women who were either prenatal or had just delivered a baby were screened for eligibility for the NFN program using the Revised Early Identification Screening Tool (Reid). The Reid screen consists of 17 items including poverty, unemployment, single head of household, substance abuse, psychiatric care or late prenatal care with a positive Reid screen score being 3 or more affirmative responses. Final eligibility for the NFN Home Visitation Program was determined using results from the Kempe Family Scale which was administered during the first home visit , 48 by tBetween November 2013 and December 2014, 117 mothers were screened for enrollment in ECHO and 57 met all initial eligibility criteria, provided consent, and were randomized into either the intervention (n = 30) or control (n = 27) arms  and tailored the NFN program using the PAT and Partners curricula (standard current practice). These curricula were then administered by home visitors. Visit documentation is kept through content logs which include information both about the visit frequency and the content of the material presented/discussed during the visit.Intervention components unique to NFN+ include: 1) enhanced support regarding breastfeeding, 2) creation of a Family Wellness Plan that teaches mothers goal-setting and self-monitoring skills to assess her family’s progress, 3) education and skill-building in behavioral strategies (problem-solving and stimulus control) to implement desired changes in four infant target areas , 4) a toolkit with items useful to support the changes, and 5) linkages to community programs that support healthy behavior change.NFN+ workers assess the mother’s attitudes and beliefs related to breastfeeding prenatally or in the hospital and provide education about the importance of breastfeeding and its benefits to the infant. After delivery, hospital staff assist new mothers in initiating breastfeeding which the NFN+ worker reinforces and supports in the home. The NFN worker observes the mother breastfeeding with special attention to the mother’s state, infant attachment, positioning, frequency, and duration of feeding. The NFN worker counsels the mother about continuing to breastfeed when returning to work and refers mothers experiencing difficulties to Heritage and Pride, a breastfeeding support program in Hartford , 49. Whi©, visits to Farmer’s Markets/corner stores), activity programs  at the BFF Centers, and parenting classes. Mothers are encouraged to set small, personally meaningful and important goals and to document their goals and progress using self-monitoring calendars and a scrapbook (containing her Family Wellness Plan) created with her NFN+ worker.This dynamic document is created in a partnership between the mother and the NFN+ worker. NFN+ workers teach mothers SMART goal setting principles  and assist mothers in setting goals regarding their and their child’s health behaviors. A plan for self-monitoring behaviors, specific to the behavior (s) selected for the Family Wellness Plan, is determined. Self-monitoring calendars are used to document behaviors and are reviewed at each visit. Maternal success in achieving her goals is emphasized. The following specific behavioral targets are emphasized as goals: extending breastfeeding duration and exclusivity, no SSB/juice consumption until 6 months and then less than 6 oz/day for the next 6 months, no solids before 6 months of age and no cereal in bottles, improving parenting skills by establishing daily routines, reading infant cues related to sleep, hunger and satiety and infant physical activity (“Tummy Time”), no television viewing, and no television in the bedroom. As mothers are successful with these infant-directed targets, NFN+ workers begin to discuss ways to create a healthier food and activity environment for the mother utilizing nutrition programs . When needed or appropriate, childcare and bus tokens are provided to facilitate use of these community programs. Intervention mothers are provided with fruit and vegetable coupons ($3/week) that they can use at local grocery stores and Farmers Markets. Mothers are provided with a pedometer to help track their steps each day. In addition, mothers can choose a “bonus” item such as cookware, a water filter system, bus passes, running shoes for themselves or a stroller. These bonus items were chosen because NFN workers noted that families were not able to participate in various activities such as cooking or exercise classes or walking activities because they didn’t have necessary items.Each intervention module includes linkages to relevant community programs  Fig. . AssesseThreats to internal validity include family mobility, the population and neighborhood comparability, and their representativeness. To address these threats, we have limited eligibility criteria, paired the neighborhoods using important variables, and have sequentially enrolled eligible mothers to the target number per neighborhood. Hartford families return to the same Brighter Future Family Center and to the same clinic  and theThis is an initial efficacy trial that is constrained by the size of the budget. However, 60 participants with a 20 % drop out rate is sufficient to detect a decrease of approximately 0.3 in the proportion of children under 6 months of age receiving SSB/juice and/or solid food with a power of 80 % and an alpha = 0.05.The primary outcome measure is the duration and exclusivity of breastfeeding, the time to consumption of SSB/juice and solids, the amount of television/screen time per day, and sleep duration in NFN+ infants as compared to NFN infants. The quality of the randomization and the comparability of the participants have been assessed using >Chi square and t-tests as appropriate Table . Particiz-score between NFN+ and NFN infants, weight categories based on weight for length percentiles will be compared using chi-square analysis.Secondary aims which compare NFN+ to NFN mothers related to a) consumption of fruits and vegetables and b) utilization of the Brighter Future Family Centers will be analyzed similar to the primary hypotheses. For the comparison of weight for length New models and interventions to prevent childhood obesity and reverse the staggering increases in obesity prevalence over the past 40 years are needed. Interventions need to not only be successful but to also be capable of wide dissemination and implementation at reasonable cost.The Early Childhood Obesity Prevention Program (ECHO) is a randomized controlled trial testing the efficacy of the early establishment of healthy behaviors in preventing childhood obesity in mothers of Latino and Black children from a low-income, urban community. It is an innovative, ecologically- and culturally-based intervention to obesity prevention. The intervention builds upon an existing home visitation program by incorporating maternal education with skill-building . The intervention then uses these core behavioral strategies to target 4 specific areas of behavior change  that mothers are open to change. The intervention has been designed to be incorporated into ongoing home visits which will enhance opportunities for wide dissemination. The intervention is also grounded in Behavior Theory and the Ecological Model of Childhood Obesity to activate mothers to implement new behaviors in the home. The intervention links mothers to community programs and resources, supports maternal changes, and provides feedback on achievement of specific goals determined by the mother within a culturally responsive framework. It also addresses concerns in Latina and Black mothers about weight as a sign of health, breastfeeding, television as an educational tool, and outdoor safety. The study is innovative in its focus on newborns, the use of mothers as agents of change, and the utilization of an existing home visitation program to enhance mother-infant outcomes. The intervention also sets the stage for lasting and endurable change by taking into account the child’s environmental and social milieu and connecting families to neighborhood programs and resources to support behavior change.


A growing body of evidence demonstrates that text messaging-based programs (short message service [SMS]) on mobile phones can help people modify health behaviors. Most of these programs have consisted of automated and sometimes interactive text messages that guide a person through the process of behavior change.This paper provides guidance on how to develop text messaging programs aimed at changing health behaviors.Based on their collective experience in designing, developing, and evaluating text messaging programs and a review of the literature, the authors drafted the guide. One author initially drafted the guide and the others provided input and review.Steps for developing a text messaging program include conducting formative research for insights into the target audience and health behavior, designing the text messaging program, pretesting the text messaging program concept and messages, and revising the text messaging program.The steps outlined in this guide may help in the development of SMS-based behavior change programs. A growing body of evidence indicates that text messaging-based programs (short message service [SMS]) on mobile phones can help people modify health behaviors -3. Text Text messaging-based programs may be effective for several reasons . Text meGiven the widespread use of texting and mobile phones and the evidence base to support their use, numerous text messaging programs have been developed globally. Current initiatives by the World Health Organization (WHO) such as “Be He@lthy, Be Mobile” and other governmental initiatives exist to address noncommunicable diseases and other health issues worldwide . While tThis paper supports the development of text messaging programs for behavior change and provides guidance on the steps to develop such a program. To date, few published resources exist that describe the process of developing a text messaging program for health behavior change ,14, and The authors drew from the evidence base in recommending specific steps for designing and developing text messaging programs, though this evidence was limited . Where Text messaging programs should follow the same phases of development that are typical for any health communication material . As withMaking Health Communication Programs Work [Health behavior change goals should be selected based on a balance of health priorities and characteristics of the target audience, such as readiness to change. For example, the target audience may be pregnant smokers and the behavior change goal may be smoking cessation among those who are interested in quitting. For a more detailed discussion on choosing a behavior change goal and selecting a target audience, see the National Cancer Institute (NCI)’s ams Work . One conams Work . In the ams Work .Consideration needs to be given to the communication objectives and behavioral techniques that will be used to promote change in the targeted behavior. Communication objectives generally consist of beliefs, attitudes, and knowledge that people will learn by participating in a given program , and behOnce communication objectives and behavioral techniques are identified, consideration should be given to how they can be supported by the attributes of text messaging as a modality. Some theoretical constructs may be especially well-suited to mobile communication, such as the Health Belief Model’s construct of cue to action  and the We recommend a logic model or behavioral schematic to outline how a particular program’s text message components (inputs) fit with theoretical constructs and proximal and longer-term behavioral and health outcomes. The framework for the program provides an overarching plan of how messages are sent to users. The framework should include a description of the timing and frequency of messages, as well as indicate the kinds of messages that will “check-in” on users (surveys) and the keywords users will be able to use to ask for additional help in times of need. For an example of a framework and message library, see the QuitNowTxt message library . In desiThe frequency of messages should address the need for the program to communicate key information without overwhelming or burdening the user. Often, text messaging programs send out at least one message/day during key behavior change periods and fewer messages  in less acute phases. Depending on the health behavior being targeted, fewer or more text messages per day may be appropriate. For example, Text2Quit sends 5 messages on the quit date, daily messages in the first week after the quit date, and 3 messages per week in the weeks after that . For useThe science on message frequency and quantity has not yet identified the ideal “dose.” Poorman et al  suggesteThe timing of messages may be related to both the content of the messages , the daily routine of the user , and the nature of the behavior change . Consideration also needs to be given to what will trigger the messages . In Papua New Guinea, a text messaging program aimed at providers treating malaria patients was found to be most acceptable in the mornings and during work hours, to help facilitate the usefulness of the reminders . While 2Interaction, or bidirectional messaging, is helpful to promote engagement in a program. Shneiderman lists “Eight Golden Rules of Interface design,” of which the following may be especially relevant for SMS programs: provide consistency, offer short-cuts, offer error prevention  and provide responsive feedback for user-initiated actions . Opportu. For example, in Text2Quit, some messages come from a fictitious quit pal who offers social support . In other programs, users are paired with an actual quit buddy to interact via text and who supports their quit attempt [The source of text messages is generally the program name , so it is easily recognized by the participant as coming from the program. However, automated messages may be supplemented with messages from a real person/counselor/clinician. Even within automated program messages, the message source can vary with some messages coming from the program and others from a specific “person” who is part of the program attempt .A decision has to be made as to whether the program will run as a single generic program, with all users receiving the same content, whether there will be different versions (or protocols) for different types of users, or even whether individually tailored versions of the program may be offered. In general, creating extra protocols or tailoring to individual characteristics can be more expensive and therefore should be carefully thought through ahead of time. Tailored protocols may be considered because they can result in higher readership, higher message recall, perceptions of higher personal relevance, and in some cases, greater behavior change . Some evModels of mobile programs include programs that stand alone   or progrText messaging is not a secure technology and, therefore, has risks associated with it for transmitting personal health information. This is especially a sensitive issue when programs will include personal health information and originate from a Health Insurance Portability and Accountability Act (HIPAA) covered entity, within the US context , or meetThe message library is a database of specific messages that will be sent to the user. Messages need to be written for each case supported by the program. Messages need to be 160 characters (including spaces) or less to be delivered as a single text message to a mobile phone, unless the users have smartphones. When necessary, messages may be split between 2 text messages to accommodate additional content. For an example of an existing message library, see QuitNowTxt message library . Once wrThe following are some considerations when writing the message library.Messages can be based on many behavioral approaches including providing information or advice, asking users to track behaviors, providing feedback on goals, offering reminders, providing positive reinforcement, or providing social support , or informal punctuation . Our experience is that users find this type of language to be unprofessional coming from a credible health source. According to Ranney et al , even teOnce the message library is drafted, check the literacy demands associated with the messages. This can be done using the Flesch-Kincaid Grade Level Test or Flesch Reading Ease test tool to determine the readability of the messages. In general, shorter words and sentences have lower literacy demands. Generally, for an adult audience, an 8th-grade reading level is considered the maximum recommended reading level , and in Given that mobile phone penetration is at 64% among adults in the United States , and theThe message library can be written to include periodic check-ins about the program’s success. These may take the form of surveying users about behavior change of interest . These offer the opportunity to redirect program messaging for the user , as well serve the purpose of providing valuable data on participant engagement and a program’s success . RemindeOnce the program is designed, we suggest building in a pretesting phase to solicit feedback on the program and the specifics of the message library. Based on feedback from this phase, revisions should be made to improve the program. Ideally, this process should be iterative and involve multiple rounds of revisions and feedback . The folPrior to Launch, Conduct Interviews With Target Audience Members to Test the Program and Sample MessagesIn these interviews or focus groups, describe the program to potential users, show them the message library (or portions of it), and ask for feedback on specific messages . Users Launch Program for PilotThere are a number of easy-to-use SMS platforms that provide the opportunity to set up a program using a Web-based interface that allows for the scheduling of text messages and provision of interactive surveys, keywords, and branching logic (targeted scheduling of messages and content). Some are free or low-cost programs like TextIt and Ez Texting, and are especially well-suited for use with a small group and for a limited period; however, many others exist and can be found highlighted in available resources like the mHealth Platform Compendium , the TexPilot Test the ProgramAfter the program is up and running, feedback from users can be obtained by running a short pilot test, such as 2-4 weeks in length and with as few as 10-30 participants, and surveying users about their experience ,49,51,52In addition to survey data, computer records of program use, if available, reveal program engagement, and in some cases, behavior change ,53-56. I. If a user complains about receiving too many messages, this may be an opportunity to offer a low-dose version of the program to keep the user engaged and subscribed.Additionally, the keyword STOP, a standard keyword across programs for unsubscribing , provideTest Alternate Versions of the ProgramIf possible, consider testing 2 (or more) versions of the program to evaluate users’ experiences on key decision variables . Another option is to change the program over time while monitoring key metrics of success . Once the program is launched, it is important to be aware of different dissemination processes (including public Web-based dissemination like that done for the NCI’s texting programs) so as to not contaminate any randomized controlled trials in which use of the program is assigned.IterateLike other health behavior interventions, these text messaging programs should be revised. Based on feedback from users collected through surveys and computer records of use, the programs should be constantly improved, and new versions deployed for use.Based on the authors’ experiences of designing, developing, trialing, and implementing text message behavior change programs, it is important to have a good design process. Perhaps one of the most important factors is to be flexible and responsive to the input and feedback of your target audience: if they do not enjoy the program they may disengage.


Escherichia coli removes 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-GTP) from the nucleotide pools precluding incorporation into DNA and RNA. While 8-oxo-dGTP incorporation into DNA is mutagenic, it is not clear if 8-oxo-GTP incorporation into RNA can have phenotypic consequences for the cell. We use a bistable epigenetic switch sensitive to transcription errors in the Escherichia coli lacI transcript to monitor transient RNA errors. We do not observe any increase in epigenetic switching in mutT cells. We revisit the original observation of partial phenotypic suppression of a lacZamber allele in a mutT background that was attributed to RNA errors. We find that Lac+ revertants can completely account for the increase in β-galactosidase levels in mutT lacZamber cultures, without invoking participation of transient transcription errors. Moreover, we observe a fluctuation type of distribution of β-galactosidase appearance in a growing culture, consistent with Lac+ DNA revertant events. We conclude that the absence of MutT produces a DNA mutator but does not equally create an RNA mutator.Living in an oxygen-rich environment is dangerous for a cell. Reactive oxygen species can damage DNA, RNA, protein and lipids. The MutT protein in  A transpression . At the pression .lac operon is increased when the fidelity of RNA transcription is decreased due to error-prone RNA polymerases, error-prone transcription sequences or to the absence of auxiliary RNA fidelity factors GreA and GreB  (lacI+ to lacI−) and the epigenetic switch frequency observed in the wild-type strain  ,6. In ade strain  demonstre strain .mutT allele facilitated a unique unidirectional mutational signature, A:T → C:G transversions  and are found in Table dnaE941 allele  and the ΔmutT and ΔmutY deletion mutations   was moved into CH1118 by P1 transduction. The kanamycin resistance cassettes were removed by a pCP20 flippase reaction.All strains used in this study are derived from the wild-type sequenced , Japan)  were mov+ revertants for each strain, a bacterial culture grown in LB media, was diluted and ∼200 cells were seeded to new tubes containing fresh LB media and shaken at 37°C overnight. The cultures were then washed 3× in minimal A salts  as the sole carbon source, and onto minimal A glucose plates for viability. Only cells constitutively expressing β-galactosidase (−lacI and lacOc mutants) can form colonies on Pgal plates. Mutation frequency was determined by dividing the number of lacI− mutants by the number of viable cells in the culture.To determine the level of Lac A salts  and then culture ,21. To dlac operon expression in single cells, a bacterial culture grown in minimal A salts plus MgSO4 (1 mM) with succinate (0.2%), was diluted 1:5 in fresh medium with (ON culture) or without 1-mM TMG (OFF culture) and shaken at 37°C for 7 h. After this induction period, the two cultures were individually diluted and ∼200 cells were seeded to new tubes containing fresh medium that contained varying amounts of TMG, and shaken at 37°C for 42 h. Flow cytometry was used to determine the percentage of cells that were induced for lac operon expression (ON cells), as previously described  and a Lac+ revertant strain (CH2956) were used; the CH2956 culture was 10-fold serially diluted into CH586 to make 1 ml in total cell volume, in duplicate, and with these reconstructed Z+:Z− populations β-galactosidase assays were performed. The cell titers of the initial cultures were determined by diluting and plating onto LB plates; the number of Lac+ revertants in the initial CH586 culture was determined by plating onto minimal lactose plates, and diluting and plating onto minimal glucose plates for cell titer.A reconstruction test was performed to determine the dynamic range of the β-galactosidase assay. Overnight LB cultures of CH586  are described in Supplementary Table S1. Bacterial strains for smFISH analysis were grown in minimal A salts with succinate (0.2%) and thiamine at 37°C. The estimation of mRNA number in the cell relies on quantifying localized fluorescence and is not achieved by counting discrete spots. The number of bound probes is measured on the basis of the total fluorescence intensity (photon flux) of the spots, without requiring that individual mRNAs appear as separate spots. By performing a calibration step, the total intensity of spots in the cell can then be converted to the number of target mRNAs , 10 μl of culture was diluted into 300 μl filtered minimal A salts plus MgSO4 (1 mM) and subjected to flow cytometry analysis with GFP fluorescence measured in a BD FACSCanto II Flow Cytometer  with Diva acquisition software (Becton Dickinson) and FloJo analysis software . To monitor fluorescent cells in a culture we used a narrow gating for forward and side scattering so that the most represented cell population was evaluated. For each independent culture 10 000 cells were interrogated, as previously described . OD600 readings from the LB control wells  were subtracted from OD615 readings from wells containing the same strain with Xgal to normalize readings to account for cell growth.Overnight LB cultures of each strain were diluted and ∼200 cells were seeded into fresh LB media containing 0.5 mg/ml 5-bromo-4-chloro-3-indolyl-β-D-galactoside  in a microtiter dish (200 μl media per well) and grown at 37°C with shaking in a BioTek Synergy™ 2 multi-detection automated microplate reader. Readings were recorded every hour for 46 h  (E. coli strains: an entire deletion of the lacI gene (CH5201), the wild-type lacI promoter (CH458) and the lacI up-promoter Iq ; see Figure lacI mRNA molecules were observed in cells that have the entire lacI gene deleted. A mutant that makes about 10× more lac repressor, lacIq, has been previously isolated  ,25 to quene CH520, the wilene CH520, the wilisolated  which capromoter . smFISH ene CH520, the wiln events , making oduction .lac operon expression, we used a lacZYA::gfp construct expressing β-galactosidase, galactoside permease and green fluorescent protein , we did not observe any increase in epigenetic switch frequency compared to wild-type cells  , which is similar to mutation induction found in other studies of mutT mutagenesis in the lacI system (When we measured the epigenetic switch frequency in our bistable switch assay in a Δ) Figure . Both wis Figure . As expeI system .lac operon ON) in the same system  in a ara Δ(gpt-lac)5 thi trpE9777 background; we use the original CC101 strain 5; Table E. coli strain CC101 (CH586) measures reversion from Lac− to Lac+ specifically via the A:T → C:G transversion at codon 461 of the lacZ gene; at this site the wild-type GAG Glu codon is now a TAG amber nonsense mutation . Similarly, at the RNA level, partial phenotypic suppression (leakiness) may occur through 8-oxo-GTP incorporation opposite the same A of the amber nonsense codon on the transcribed DNA strand during mRNA transcription . As a result of 8-oxo-GTP incorporation, the 3′ATC5′ nonsense codon will be transcribed as 5′G*AG3′ (G* indicates 8-oxoG) in the nascent transcript and translated as a Glu residue by tRNA with a 3′CUU5′ anticodon sequence  compared to a mutT strain (CH4404)  Table .dnaE gene with the dnaE941 anti-mutator allele. The dnaE941 allele encodes a DNA polymerase that was isolated as a suppressor of the high mutability of a mutT mutator strain  compared to the CC101 mutT strain  versus strain CC101 mutT; Table + mutants in the bacterial culture. We emphasize that the levels of 8-oxo-dGTP and 8-oxo-GTP will be unchanged in all the mutT strains, but the DNA mutational consequences of those same levels of oxidized nucleotide pools will be different (diminished) in the mutT strains that carry the additional mutated or altered mutY and dnaE alleles. We note that cultures of the CC101 ΔmutT ΔmutY dnaE941 strain still generate over 500-fold more Lac+ mutants than the wild-type CC101 strain  is omitted from analysis, the same trend is observed as found in Table mutT allele is decreased by 61% in a CC101 ΔmutT ΔmutY strain, and 86% in a CC101 ΔmutT ΔmutY dnaE941 strain in this independent experiment (Supplementary Table S2). Again, omitting the jackpot culture, we observe a 5.3-, 3.8-, 2.7-fold increase in β-galactosidase enzyme levels for the ΔmutT, ΔmutT ΔmutY and ΔmutT ΔmutY dnaE941 strains, respectively, over that observed in the wild-type CC101 strain (Supplementary Table S2). We observe that cultures of the ΔmutT ΔmutY dnaE941 strain generate over 500-fold more Lac+ mutants than the wild-type CC101 strain, but exhibit only a 2.7-fold increase in β-galactosidase enzyme level in the culture.To concurrently study the genotypic and phenotypic effect of the absence of MutT function, we measured mutation frequency and β-galactosidase activity from the same culture in wild-type CC101, Δet al. ; the possibility that this increased β-galactosidase enzyme level in ΔmutT cultures was due to Lac+ revertant mutations arising in the growing population, i.e. 8-oxo-dGTP being incorporated opposite the template A during DNA replication, was discounted , measured in Miller units: M(pop) = M(lac+)f(lac+) + M(lac−)f(lac−) where M(lac+) and M(lac−) are β-galactosidase activities of Lac+ and Lac− cells, and f(lac+) and f(lac−) their respective frequencies . The wild-type level of β-galactosidase activity in a fully induced Lac+ CC101 culture is ∼3800 Miller units  = 0.38; f(lac+) = 10−5; M(lac+) = 38 000], because each revertant would need to produce 10-fold more β-galactosidase Miller units than the value obtained for a fully induced wild-type lacZ gene.Our result is in contrast to that of Taddei et al.  not onlyscounted . The folquencies . Therefos Figure  that themutT background, and in all the backgrounds that reduce the mutational burden of the absence of MutT function, can be readily explained solely by the generation of Lac+ DNA revertant bacteria that arise during the growth of the cultures. All the revertant Lac+ β-galactosidase levels observed in the ΔmutT strain, and the ΔmutT derivatives, approach the β-galactosidase levels made by a fully induced wild-type lacZ gene, or are less than the β-galactosidase levels made in a fully induced wild-type lacZ gene, including the ΔmutT mutation jackpot culture down to the ΔmutT ΔmutY dnaE941 background, which is a ∼400-fold difference in Lac+ mutation frequency  was 10-fold serially diluted into a CC101 LacZ− culture  and β-galactosidase assays were performed. As the number of Lac+ revertants falls, the β-galactosidase units in the reconstruction test falls in parallel until the level of 1 Z+: 106 Z− is achieved; after that point, any further dilution in Lac+ numbers does not affect the observed β-galactosidase units level which levels out at the same β-galactosidase unit level as the Z buffer ONPG control. The numbers of Lac+ revertants, and the corresponding β-galactosidase units, for CC101, ΔmutT and all other the mutT-compromised strains, including the ΔmutT jackpot culture, all fall on, or close to, the reconstruction line  is 3079 Miller units; see Table mutT ΔmutY dnaE941 strain is being effectively assayed for β-galactosidase content in the culture, while the CC101 strain is not being effectively assayed for β-galactosidase content in the culture, and the correction for this mis-monitoring would be over 100-fold.When we plot these results Figure ; Table 3mutT cultures can be accounted for by the Lac+ revertant numbers we found in the same cultures, unlike the initial study, where the β-galactosidase levels observed were stated to be too high to be accounted for by Lac+ revertant numbers , and not what was previously observed (∼30-fold) in the CC101 background (amberlacZ leakiness (1.5- versus the 30-fold increase observed before at codon 461 of lacZ in a ΔmutT background) was not addressed by Inokuchi et al.  at the position 1456 of the lacZ gene, creating an amber nonsense mutation at codon 486; incorporation of 8-oxo-GTP opposite the A of the nonsense codon on the transcribed DNA strand would allow the incorporation of a glutamic acid residue at this site that will also provide essentially the same β-galactosidase activity as the wild-type enzyme  and therefore this would be consistent with the idea that mutT-mediated mutations are not responsible for the observed increase in β-galactosidase levels in a mutT aerobic culture; in light of other studies  and cleavage of Xgal (OD615) to observe the nature of the appearance of β-galactosidase activity during growth of the CC101 and ΔmutT compromised cultures  was added to LB media , and a fs Figure . As the mutT wells exhibit an abrupt appearance of blue with the timing of color change varying from well to well. The timing of blue appearance becomes delayed and the numbers of wells that exhibit blue decreases as the mutational consequence of mutT-mediated mutagenesis is decreased. This is seen most clearly for the CC101 ΔmutT ΔmutY dnaE941 strain when singular stochastic events in a few cultures produce markedly different end results from the majority of similar cultures .When the time course of β-galactosidase enzyme activity in growing cultures is monitored Figure , the flu+ revertant events, and not a gradual constant production of β-galactosidase that should arise from chronic incorporation of 8-oxo-GTP into the lacZ transcript that would transiently produce long-lived β-galactosidase molecules that would progressively accumulate ; moreover, this gradual accumulated appearance should be similar for all ΔmutT compromised cultures, since the amount of 8-oxo-GTP is the same for all such strains. However, we see no evidence for a steady increase in blue color. Therefore, these results are completely consistent with the quantitative assay of mutation and β-galactosidase enzyme activity . However, other studies have used the suppression of blue-ness in a CC101 ΔmutT background grown in LB plus Xgal, or in a more quantitative β-galactosidase enzyme activity assay, to screen for mammalian  we do not see any enhanced phenotypic effect attributable to RNA errors. Mutation fluctuation patterns become more pronounced as we decrease the mutational burden of mutT-mediated mutagenesis. Lac+ revertants can explain the increase in β-galactosidase enzyme activity in the ΔmutT cultures. Therefore, our results suggest that 8-oxo-dGTP can have ∼500× more relative DNA mutational impact during DNA replication than the RNA mutational impact of 8-oxo-GTP during RNA transcription.The idea that persistent 8-oxo-GTP in the ribonucleotide pool, due to the absence of MutT function, can have phenotypic consequences for the cell is provocative ,26. WhenmutT cells due to the incorporation of 8-oxo-dGTP is about four per 106 guanine residues  or heritable (epigenetic switching) consequences for the phenotype of the cell, and instead suggest that the observed increase in β-galactosidase levels in the cell ,6, and wA high level of reactive oxygen species can be detrimental for cell survival because of damage to DNA, RNA, protein and lipids. Whereas the removal of oxidized dGTP by MutT is critical to reduce DNA replication errors, it remains unclear how the persistence of oxidized GTP in the nucleotide pool can trigger aminoglycoside antibiotic cytotoxicity  or increSupplementary Data are available at NAR Online.


Given the dramatic rise and impact of chronic diseases and gaps in care in Indigenous peoples in Canada, a shift from the dominant episodic and responsive healthcare model most common in First Nations communities to one that places emphasis on proactive prevention and chronic disease management is urgently needed.The Transformation of Indigenous Primary Healthcare Delivery (FORGE AHEAD) Program partners with 11 First Nations communities across six provinces in Canada to develop and evaluate community-driven quality improvement (QI) initiatives to enhance chronic disease care. FORGE AHEAD is a 5-year research program (2013–2017) that utilizes a pre-post mixed-methods observational design rooted in participatory research principles to work with communities in developing culturally relevant innovations and improved access to available services. This intensive program incorporates a series of 10 inter-related and progressive program activities designed to foster community-driven initiatives with type 2 diabetes mellitus as the action disease. Preparatory activities include a national community profile survey, best practice and policy literature review, and readiness tool development. Community-level intervention activities include community and clinical readiness consultations, development of a diabetes registry and surveillance system, and QI activities. With a focus on capacity building, all community-level activities are driven by trained community members who champion QI initiatives in their community. Program wrap-up activities include readiness tool validation, cost-analysis and process evaluation. In collaboration with Health Canada and the Aboriginal Diabetes Initiative, scale-up toolkits will be developed in order to build on lessons-learned, tools and methods, and to fuel sustainability and spread of successful innovations.The outcomes of this research program, its related cost and the subsequent policy recommendations, will have the potential to significantly affect future policy decisions pertaining to chronic disease care in First Nations communities in Canada.NCT02234973. Date of Registration: July 30, 2014.Current ClinicalTrial.gov protocol ID The online version of this article (doi:10.1186/s12961-016-0127-y) contains supplementary material, which is available to authorized users. Chronic diseases are considered to be among the most preventable of all health problems, yet WHO predicts that, in 2030, chronic diseases will be the seventh leading global cause of death . The chrThe higher rates of adverse health outcomes in Indigenous peoples are related to an array of factors, including the social determinants of health  , lifestyThe Federal Government’s role in the provision of health services to registered First Nations living on-reserve and to Inuit living in their traditional territories, is primarily through the public health and prevention services offered by the First Nations and Inuit Health Branch . Home anSustained improvements in the quality of care of chronic diseases has been achieved in the United States, Australia and Canada through the Indian Health Services national T2DM surveillance and audit/feedback programs, the Audit and Best Practice for Chronic Disease program, and the DREAM3 study, respectively –25. The These programs include various aspects of the most recognized approach to optimize chronic disease care: the Chronic Care Model (CCM)  and the The literature on primary healthcare disparities and QI interventions in Indigenous populations consistently notes that participatory research principles and cultural tailoring and competencies need to be priorities , 38. AllIn light of the fact that Canada is spending an increasing share of its revenue on healthcare yet falling behind other industrialized nations in obtaining value for its investment related to performance on safety, quality, equity and efficiency , 46, theWe detail in this paper the methods, tools and activities of the FORGE AHEAD Program. Future publications will include details and results of the process evaluation and the outcome evaluation utilized within the FORGE AHEAD Program.Assess the current healthcare delivery, funding models and best practices used in First Nations communities in CanadaAssess community and clinical readiness to address and adopt chronic disease careEnhance patient access to available community resources for chronic disease careImplement, evaluate and cost community and clinical QI initiatives to improve chronic disease managementDevelop sustainment strategies and scale-up toolkits for improved chronic diseaseThe TransFORmation of IndiGEnous PrimAry HEAlthcare Delivery (FORGE AHEAD): Community-driven Innovations and Strategic Scale-up Toolkits was funded by this initiative as a 5-year national research program that partners with Indigenous communities in Canada to improve chronic disease care and access to available resources by developing and evaluating community-driven, culturally-relevant primary healthcare models through a QI process . The proFORGE AHEAD partnered with 11 First Nations communities across six provinces  and three isolation levels  , the Health Research Ethics Board of Alberta , the Cree Board of Health and Social Services of James Bay , Mi’kmaw Ethics Watch, Unama’ki College, Cape Breton University , and Mi’kmaq Confederacy Ethics Review Committee, Prince Edward Island . The FORGE AHEAD program is grounded in the guiding principles of: (1) community-based participatory research (CBPR) and the Ownership, Control, Access, and Possession® Principles  describeFigure The FORGE AHEAD Program is encompassed by a series of 10 inter-related and progressive activities separated into three components, namely, national-level preparatory activities, community-driven intervention activities and wrap-up/dissemination. Community participation spans a total of 18-months for all activities Fig. .Fig. 3FOAll communities partnering in the program are asked to complete a Community Profile Survey (CPS) Activity 1) to identify and describe current healthcare delivery, funding models, available infrastructure , T2DM programs, and the number of health professionals working in their community, both part-time and full-time  was also completed in 2015 and involved a synthesis of healthcare policy up to 2008 relevant to Indigenous communities to identify and describe existing healthcare policies affecting Indigenous communities and best practices developed by and for Indigenous communities. A systematic review of peer-reviewed and grey literature was conducted and published . The knoThe Community Readiness Model (CRM) for community change integrates a community’s culture, resources, level of knowledge, and support to determine the level of readiness to address an issue . ReadineCommunity Readiness Consultation (Activity 5), the first step of the intervention, uses the Community Readiness Consultation Tool developed during the preparatory phase to facilitate discussions within the Community Team of three to five members  to begin brainstorming ideas for the development of chronic disease initiatives. Similarly, the Clinical Readiness Consultation (Activity 6) utilizes the Clinical Readiness Consultation Tool within the Clinical Team. After each team member individually completes their respective tool, the Western research team develops aggregated reports that summarize the results across the team members. Community Facilitators, hired and trained by the Western research team, guide their teams in completing the tools and lead discussions at round-table meetings with each of their teams to review, share and discuss summarized results. Each team has an opportunity to change the scores on their reports based on team consensus before proceeding to use the report to identify key factors and priorities for the development of chronic disease innovations. The readiness tools are completed by each team member three times during the course of the program. Each time, aggregated reports are developed and reviewed by each team. The ultimate aim of these reports is to facilitate discussions by each team to align their chronic disease initiatives to their degree of readiness, thereby increasing the likelihood that the initiatives will lead to improvements.Community-driven (Activity 7) and Clinical (Activity 8) QI Initiatives includes a series of three workshops (1–2 days), separated by 3-month action periods.Each workshop involves three parts: (1) plenaries with expert presenters for all teams to learn about priority topics as a group; (2) individual team sharing of key community strengths, progress and challenges to enable cross community learning and support; and (3) breakout sessions where individual teams are allotted dedicated time together to discuss their readiness reports and plan their QI initiatives using the Model for Improvement , 58 inclBuilding on previously successful QI initiatives, the program includes the development of a registry , 59. IdePost Community Readiness and post Clinical Readiness Consultations will be conducted to assess community readiness and clinical readiness at program’s end. In addition, both readiness tools will undergo a validation process to develop and implement innovations in improving chronic care prevention and management in First Nations communities.To evaluate the success of the FORGE AHEAD Program, a comprehensive (process and outcome) evaluation will be used and facilitated by the development of a logic model of the program. The logic model development will be guided by the worksheets of the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE) , 60 and Analyses (Activity 10) will include a cost analysis to determine the cost of implementing the intervention  in First Nations communities. It is important to be able to quantify the cost of the quality improvement initiatives to inform sustainability and scale-up initiatives. In-depth process evaluations, including key stakeholder interviews  will be held to gain knowledge on their perceptions of various QI activities/application/benefits. Process evaluation will also include a detailed review of all program documentation to identify details about program activities and the implementation process, and to learn about the experience of those who participated in the program and their perceptions of the impact of the research program in their individual communities. The Western research team will work with partnering communities to determine the completeness of their surveillance system. Support will be provided to the Community Data Coordinators to update the system as needed to support the evaluation of the intervention.FORGE AHEAD will produce a toolkit of tested tools and strategies that can be successfully implemented, sustained and used for diabetes and other chronic diseases in First Nations communities across Canada. Scale-up toolkits will be developed by integrating tools and best practices between Health Canada and the FORGE AHEAD Research Program. Toolkits and all results of the program will be disseminated to each partnering community prior to undertaking national and international dissemination efforts.www.tndms.ca/forgeahead/) that houses resources, program documents and support documents, a FORGE AHEAD Facebook page (www.facebook.com/FAProgram), and quarterly newsletters have been a critical platform for updating all team members and building camaraderie.The principles of CBPR support integrated and end-of-program KT with communities involved as equal partners in the research process . CommuniThe FORGE AHEAD Program is in its fourth year and still being implemented. A chronic disease approach is promoted and is being laid through the development of QI innovations by community and clinical teams in partnering communities. Successful models of care are being rapidly identified and tested using the PDSA cycle, and the conditions necessary for sustainment and scale-up of successful innovations are being investigated throughout the process. Planning for and implementing integrated and program-end KT is ahead of schedule as well as the development the FORGE AHEAD Scale-up Toolkits.Comprehensive data on the recruitment and retention of partnering communities, and community and clinical team members is not yet available. At program end, complete evaluation data will be available detailing the use of all FORGE AHEAD tools, including the Community and Clinical Readiness tools, the First Nations Diabetes Sentinel Surveillance System, and all QI tools used to facilitate the development of community-driven initiatives. The impact of these tools on health-related outcomes, the cost of implementing the various activities within the program, and detailed process evaluations including the logic model, participant observation, project documentation reviews and community interviews will inform further revisions to all tools as well as inform best practices for the successful implementation and scale-up of the program.Indigenous communities in Canada represent a unique challenge for our healthcare system with soaring rates of chronic diseases, a wide array of funding and service models, and distinctive barriers to providing optimal care. Despite recent efforts to fund more chronic disease-oriented initiatives and programs, rates of chronic diseases such T2DM continue to rise and the gap between Indigenous and non-Indigenous peoples continues to widen. In Indigenous settings, community engagement and participation is crucial to identifying and developing successful and sustainable innovations that can improve access to essential and culturally relevant chronic disease-focused primary healthcare services with the ultimate goal of reducing inequities in health.The FORGE AHEAD Program set out to promote and evaluate the development of community-driven, culturally relevant, primary healthcare models that enhance chronic disease management and appropriate access to available services in First Nations communities across Canada. The program is implemented in two waves with 11 First Nations communities across seven provinces and utilizes a participatory research approach recognizing communities as true partners. As partners, their contribution to the program from the inception of the research design to implementation of the program activities is acknowledged and appreciated as a critical grass-roots perspective that will help bring to the centre of efforts the Indigenous voice that is necessary in order to succeed.Some of the practical challenges to this type of work are the cost of developing and implementing such programs in remote locations, the lack of resources available within the community, and the long timelines needed to establish rapport and trusting relationships. The FORGE AHEAD team has been fortunate in securing additional funding to support the program and with the expertise housed on our experienced and skilled team, the program is being successfully implemented. It is important to note that in-kind contributions by many of the FORGE AHEAD Program team members from co-investigators, collaborators, knowledge-users and decision-makers, and elders, leaders and key contacts in partnering communities have helped to build a meaningful and solid foundation as FORGE AHEAD progresses into its final year of implementation. Limited funding has restricted the number and type of in-person collaborations; however, new electronic platforms have been successfully employed to build and sustain strong relationships with community partners and enhanced the capacity of this team, which is spread across the country, to function virtually. Our KT efforts include a Facebook site designed to build camaraderie and support, a website that houses all program materials and documents accessible by all team members at any time, program newsletters that include spotlights of key successes and updates, and the use of teleconferencing and videoconferencing technology.Critical factors related to the on-going success of the program to date have been identified, including the large team’s leadership and depth of interdisciplinary research/practice, key community personnel who are champions in their communities leading the QI work, the capacity to develop new partnerships and obtain additional funding to ensure true participatory research, enhancement of capacity building and training opportunities, and networking and incorporating a wide variety of integrated and program-end KT activities. Preliminary process evaluation results reveal the important role of the Community Facilitators and Community Data Coordinators who are committed, skilled and respected leaders in their communities. The strength of the FORGE AHEAD Program lays within the team – the commitment, the leadership, the experience and the diverse skill set of people who are passionate about improving the lives of people living with diabetes by decreasing the health, clinical and financial burden of diabetes in Indigenous communities.The outcomes of the FORGE AHEAD Program, its related cost and the subsequent policy recommendations have the potential to support the redesign of chronic disease care and management in First Nations communities across Canada. Results may significantly affect future chronic disease policy decisions pertaining to First Nations communities.CBPR, community-based participatory research; CCM, chronic care model; CPS, community profile survey; CRM, community readiness model; DEFINE, diabetes evaluation framework for innovative national evaluations; ECCM, expanded chronic care model; FORGE AHEAD, transformation of Indigenous primary healthcare delivery: community-driven innovations and strategic scale-up toolkits; HbA1C, glycosylated haemoglobin; KT, knowledge translation; PDSA, plan-do-study-act; QI, quality improvement; T2DM, type 2 diabetes mellitus.