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Abstract Background Digital, or eHealth, interventions are highly promising approaches to help adolescents improve their health behaviours and reduce their risk of chronic disease. However, they often have low uptake and retention. There is also a paucity of high-quality research into the predictors of eHealth engagement, and a lack of studies that have systematically evaluated existing engagement strategies in adolescent populations. This paper describes the protocol for a randomised controlled trial which primarily aims to assess the effectiveness of different strategies in increasing engagement with a healthy lifestyles app, Health4Life. Associations between the engagement strategies and improvements in adolescent health behaviours (healthy eating, physical activity, sleep, recreational screen time, smoking, alcohol use) will also be examined, along with potential predictors of adolescents’ intentions to use health apps and their use of the Health4Life app. Methods The current study will aim to recruit 336 adolescent and parent/guardian dyads (total sample N = 672) primarily through Australia wide online advertising. All adolescent participants will have access to the Health4Life app (a multiple health behaviour change, self-monitoring mobile app). The trial will employ a 24 factorial design, where participants will be randomly allocated to receive 1 of 16 different combinations of the four engagement strategies to be evaluated: text messages, access to a health coach, access to additional gamified app content, and provision of parent/guardian information resources. Adolescents and parents/guardians will both complete consent processes, baseline assessments, and a follow-up assessment after 3 months. All participants will also be invited to complete a qualitative interview shortly after follow-up. The primary outcome, app engagement, will be assessed via an App Engagement Index (Ei) using data collected in the Health4Life app and the Mobile App Rating Scale – User version. Discussion This research will contribute significantly to building our understanding of the types of strategies that are most effective in increasing adolescents’ engagement with health apps and which factors may predict adolescents’ use of health apps. Trial registration The trial is registered at the Australian New Zealand Clinical Trials Registry (ACTRN12623000399695). Date registered: 19/04/2023.

Abstract Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR. We show that these variants specifically reduce insertion-deletion outcomes without increasing off-target editing, synergize with a DNAPK inhibitor molecule, and can be applied at manufacturing scale to increase the fraction of cells bearing repaired alleles. This screening platform can enable the discovery of future gene editing reagents that improve HDR outcomes.

Abstract Our comment discusses our experience establishing a youth advisory group focused on chronic disease prevention research. The comment highlights three key learnings: the need for researchers to adapt their working style, the importance of redefining the power dynamics, and disrupting traditional research structures to align with co-researcher engagement models.

Abstract Background Diets low in vegetables are a main contributor to the health burden experienced by Australians living in rural communities. Given the ubiquity of smartphones and access to the Internet, digital interventions may offer an accessible delivery model for a dietary intervention in rural communities. However, no digital interventions to address low vegetable intake have been co-designed with adults living in rural areas. This paper describes the co-design of a digital intervention to improve vegetable intake with rural community members and research partners. Methods Active participants in the co-design process were adults ≥ 18 years living in three rural Australian communities (total n = 57) and research partners (n = 4) representing three local rural governments and one peak non-government health organisation. An iterative co-design process was undertaken to understand the needs (pre-design phase) and ideas (generative phase) of the target population. Eight online workshops and a community survey were conducted between July and December 2021. The MoSCoW prioritisation method was used to help participants identify the ‘Must-have, Should-have, Could-have, and Won’t-have or will not have right now’ features and functions of the digital intervention. Workshops were transcribed and inductively analysed using NVivo. Convergent and divergent themes were identified between the workshops and community survey to identify how to implement the digital intervention in the community. Results Consensus was reached on a concept for a digital intervention that addressed individual and food environment barriers to vegetable intake, specific to rural communities. Implementation recommendations centred on (i) food literacy approaches to improve skills via access to vegetable-rich recipes and healthy eating resources, (ii) access to personalisation options and behaviour change support, and (iii) improving the community food environment by providing information on and access to local food initiatives. Conclusions Rural-dwelling adults expressed preferences for personalised intervention features that can enhance food literacy and engagement with community food environments. This research will inform the development of the prototyping (evaluation phase) and feasibility testing (post-design phase) of this intervention.

Abstract Background Adolescents are navigating a period of rapid growth and development within an era of digitalization. Mobile phone ownership among adolescents is nearly ubiquitous, and this provides an opportunity to harness text messaging to promote a healthy lifestyle and reduce chronic disease risk factors. Inclusion of adolescents throughout the design process has been recognized as essential for engagement and future implementation of such interventions. This study aimed to co-design a bank of text messages to promote a healthy lifestyle which are useful, acceptable, and engaging for adolescents aged 12–18 years old. Methods Iterative, mixed-methods design with consumer partnership. Co-design occurred over three stages: text message development, text message review and final refinement and testing. The text message development included literature searches and consumer partnership with an established youth advisory group (n = 16). Participants who gave e-consent participated in text message review. Demographic characteristics were collected, and quantitative surveys were distributed to adolescents (n = up to 50) and health professionals (n = up to 30), who rated text message content for understanding, usefulness and appropriateness (total score out of 15). Final refinement was completed by the research team to edit or remove messages which had low scores and to assess readability and interactivity of the text messages. Results The Heath Advisory Panel for Youth at the University of Sydney (HAPYUS) identified the top six lifestyle health issues for young people today in relation to chronic disease prevention, which became the key content areas for the text message bank and drafted new text messages. Following text message development, 218 messages were available for review. Adolescents (n = 18, mean age 16.3 [SD 1.4]) and healthcare professionals (n = 16) reviewed the text messages. On average, all reviewers found that the text messages were easy to understand (mean = 13.4/15) and useful (mean = 12.7/15). Based on scoring and open ended-feedback, 91 text messages were edited and 42 deleted. The final text message bank included 131 text messages. The overall program is suitable for a seventh-grade reading level, and interactive. Conclusions This study describes the process of effectively engaging adolescents to co-design a text message bank intervention, which are useful, acceptable and engaging for an adolescent audience. The effectiveness of the co-designed text message bank is currently being tested in the Health4Me RCT.

BackgroundChronic disease risk factors are increasing amongst adolescents, globally. Digital health prevention programs, which provide education and information to reduce chronic disease risk factors need to be equitable and accessible for all. For their success, multiple highly engaged stakeholders should be involved in development and implementation. This study aimed to evaluate stakeholders’ support for, and perspectives on potential public health impact of digital health prevention programs for adolescents and potential pathways for future implementation.MethodsQualitative semi-structured online interviews with stakeholders. Stakeholder mapping identified key individuals, groups and organizations across Australia that may influence the implementation of digital health prevention programs for adolescents. Recorded and transcribed interviews were analyzed within the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) Framework, using deductive content analysis.FindingsNineteen interviews were conducted in 2023 with stakeholders from government, health, non-government organizations, youth services, education, community settings and others. Four overarching themes were identified: (i) existing digital health initiatives are not fit for purpose; (ii) the co-creation of digital health prevention programs is critical for successful implementation; (iii) digital health prevention programs must address equity and the unique challenges raised by technology and; (iv) system level factors must be addressed.InterpretationStakeholders broadly supported digital health prevention programs, yet raised unique insights to ensure that future programs create public health impact by improving chronic disease risk factors among adolescents. These insights can be applied in future development of digital health prevention programs for adolescents to strengthen widespread implementation.

Abstract Background Youth Advisory Groups (YAGs) represent a promising method to engage adolescents in research of relevance to them and their peers. However, YAGs are rarely implemented or evaluated in chronic disease prevention research. The aims of this study were firstly, to evaluate the effect of participation in a 12-month YAG on adolescents’ leadership skills and perceptions related to chronic disease prevention research and secondly, to evaluate the process of establishing and facilitating a 12-month YAG and identify barriers and enablers to establishment and facilitation. Methods This study was a 12-month pre-post study. Eligible participants were adolescents (13-18-years) and current members of an established YAG. Data collection involved online surveys and semi-structured interviews at baseline, six-months and 12-months follow-up. Participatory outcomes such as self-efficacy, leadership skills, and collective participation were derived from Youth Participatory Action Research Principles (YPAR), and the Lansdown-UNICEF conceptual framework for measuring outcomes of adolescent participation. Process evaluation data were captured via meeting minutes, Slack metrics and researcher logs. Quantitative data was analysed using descriptive statistics and qualitative data was thematically analysed using a reflexive thematic analysis approach. Results Thirteen (13/16) YAG youth advisors consented to participate in the evaluation study (mean age 16.0 years, SD 1.3; 62% (8/13) identified as female). Survey data assessing participatory outcomes found an increase in leadership and life skills scores over 12-months (+ 8.90 points). Semi-structured interview data collected over the 12-month term revealed three key themes namely: influence, empowerment, and contribution. Comparison of pre-post themes determined a positive trend at follow-ups, demonstrating improved participatory outcomes. Process indicators revealed that at 12-month follow-up the YAG was implemented as planned. Semi-structured interview data determined barriers to YAG facilitation included time and limited face-to-face components, while enablers to YAG facilitation included flexibility, accessible delivery methods, and a supportive adult facilitator. Conclusion This study found that a YAG fostered positive participatory outcomes and unique opportunities for youth participants. A successful YAG based on YPAR principles requires researchers to ensure YAG establishment and facilitation is an iterative process. Taking into consideration important barriers and enablers to YAG facilitation ensures adolescent engagement in a YAG is both meaningful and impactful.

Abstract Objective: It is unknown how well menu labelling schemes that enforce the display of kilojoule (kJ) labelling at point-of-sale have been implemented on online food delivery (OFD) services in Australia. This study aimed to examine the prevalence of kJ labelling on the online menus of large food outlets with more than twenty locations in the state or fifty locations nationally. A secondary aim was to evaluate the nutritional quality of menu items on OFD from mid-sized outlets that have fewer locations than what is specified in the current scheme. Design: Cross-sectional analysis. Prevalence of kJ labelling by large food outlets on OFD from August to September 2022 was examined. Proportion of discretionary (‘junk food’) items on menus from mid-sized outlets was assessed. Setting: Forty-three unique large food outlets on company (e.g. MyMacca’s) and third party OFD (Uber Eats, Menulog, Deliveroo) within Sydney, Australia. Ninety-two mid-sized food outlets were analysed. Participants: N/A. Results: On company OFD apps, 35 % (7/23) had complete kJ labelling for each menu item. In comparison, only 4·8 % (2/42), 5·3 % (2/38) and 3·6 % (1/28) of large outlets on Uber Eats, Menulog and Deliveroo had complete kJ labelling at all locations, respectively. Over three-quarters, 76·3 % (345/452) of menu items from mid-sized outlets were classified as discretionary. Conclusions: Kilojoule labelling was absent or incomplete on a high proportion of online menus. Mid-sized outlets have abundant discretionary choices and yet escape criteria for mandatory menu labelling laws. Our findings show the need to further monitor the implementation of nutrition policies on OFD.

This study protocol discusses the co-design and co-development of a social media health promotion program for young women. The program aims to disseminate evidence-based health information and promote healthy behaviours among young women aged 18–24 years. The evidence-base for social media interventions is explored, with examples of successful health promotion programs using social media platforms for example, Facebook. The social media health promotion program has been developed in four phases, including a literature review, interviews and workshops with young women, dietitians, digital marketers and marketing and nutrition academics, co-design and development of the program, and a feasibility study. The feasibility study will be using a mixed-methods approach, including surveys, focus groups, and social media analytics. Overall, this protocol highlights the potential of social media as a platform for promoting health behaviours among young adults and provides a framework for the co-design and co-development of evidence-based health promotion programs using social media.

Introduction Diets low in vegetables are a main contributor to the health burden experienced by young adults in rural communities. Digital health interventions provide an accessible delivery model that can be personalised to meet the diverse preferences of young adults. A personalisable digital vegetable intake intervention (Veg4Me) was codesigned to meet the needs of young adults living in rural communities. This study will determine the feasibility of delivering a personalised Veg4Me programme and compare preliminary effects with a non-personalised Veg4Me (control).Methods and analysis A 12-week assessor-blinded, two-arm, parallel randomised controlled trial will be undertaken from August 2023 until April 2024. A total of 150 eligible and consenting young adults (18–35 years; eat

Introduction Innovative health promotion strategies are crucial for enhancing global quality of life and curbing premature deaths. Digital health promotion is particularly impactful for young individuals often using internet-connected devices. Collaborative methodologies in digital intervention research offer insights into supporting youth during key life stages, such as adolescence. This review sought to examine the literature on digital health interventions for youth co-designed via participatory frameworks. Methods Following the Joanna Briggs Institute Manual and an adapted Arksey & O’Malley's 6-stage framework, this review utilised the PRISMA-ScR checklist for structured reporting. Peer-reviewed research where young individuals (15–35 years) contributed to digital health intervention design was analysed. Systematic synthesis adhered to Braun & Clarke's Thematic Analysis Guidelines, mapping data to research queries and thematic framework. Results Eighteen articles were systematically synthesised, revealing seven main themes: digital tool, inquiry field, report aim, participatory activities, intervention attributes and behavioural change support. Seventeen distinctive digital health interventions were assessed, mostly within risk mitigation and mental health domains. Predominantly, interventions were web-based, with mental wellness websites emerging as the prevalent tool. User experience testing stood out as the primary reported outcome. Conclusion Several innovative digital health interventions targeting youth have been identified. Platforms including social media, specialised apps, websites and video games are instrumental for health advice and clinical support dissemination, overcoming access and cost barriers. Participatory techniques are integral for the efficacy of digital health resources, encompassing youth aspirations and anticipations. Continued efforts will enrich comprehension of optimal practices in digital health promotion and intervention formulation.

Abstract Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, evolutionary history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a most recent common ancestor in 2018 carrying a low-fitness cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri. Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.

Abstract Background Adolescent consumer engagement is widely accepted, with global calls to meaningfully involve adolescents for effective and tailored policy and guideline development. However, it is still unclear if and how adolescents are engaged. The aim of this review was to determine if and how adolescents meaningfully participate in policy and guideline development for obesity and chronic disease prevention. Methods A scoping review was conducted guided by the Arksey and O’Malley six stage framework. Official government websites for Australia, Canada, United Kingdom, and United States including intergovernmental organizations (World Health Organisation and United Nations) were examined. Universal databases Tripdatabase and Google advanced search were also searched. Current and published international and national obesity or chronic disease prevention policies, guidelines, strategies, or frameworks that engaged adolescents aged 10–24 years in meaningful decision-making during the development process were included. The Lansdown-UNICEF conceptual framework was used to define mode of participation. Results Nine policies and guidelines (n = 5 national, n = 4 international) engaged adolescents in a meaningful capacity, all focused on improving ‘health and well-being’. Demographic characteristics were poorly reported, still most ensured representation from disadvantaged groups. Adolescents were primarily engaged in consultative modes (n = 6), via focus groups and consultation exercises. Predominantly in formative phases e.g., scoping the topic or identifying needs (n = 8) and to a lesser extent in the final stage of policy and guideline development e.g., implementation or dissemination (n = 4). No policy or guideline engaged adolescents in all stages of the policy and guideline development process. Conclusion Overall, adolescent engagement in obesity and chronic disease prevention policy and guideline development is consultative and rarely extends throughout the entire development and implementation process.

Abstract Background Digital interventions may help address low vegetable intake in adults, however there is limited understanding of the features that make them effective. We systematically reviewed digital interventions to increase vegetable intake to 1) describe the effectiveness of the interventions; 2) examine links between effectiveness and use of co-design, personalisation, behavioural theories, and/or a policy framework; and 3) identify other features that contribute to effectiveness. Methods A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Scopus, CINAHL, Cochrane Library, INFORMIT, IEEE Xplore and Clinical Trial Registries, published between January 2000 and August 2022. Digital interventions to increase vegetable intake were included, with effective interventions identified based on statistically significant improvement in vegetable intake. To identify policy-action gaps, studies were mapped across the three domains of the NOURISHING framework (i.e., behaviour change communication, food environment, and food system). Risk of bias was assessed using Cochrane tools for randomized, cluster randomized and non-randomized trials. Results Of the 1,347 records identified, 30 studies were included. Risk of bias was high or serious in most studies (n = 25/30; 83%). Approximately one quarter of the included interventions (n = 8) were effective at improving vegetable intake. While the features of effective and ineffective interventions were similar, embedding of behaviour change theories (89% vs 61%) and inclusion of stakeholders in the design of the intervention (50% vs 38%) were more common among effective interventions. Only one (ineffective) intervention used true co-design. Although fewer effective interventions included personalisation (67% vs 81%), the degree of personalisation varied considerably between studies. All interventions mapped across the NOURISHING framework behaviour change communication domain, with one ineffective intervention also mapping across the food environment domain. Conclusion Few digital interventions identified in this review were effective for increasing vegetable intake. Embedding behaviour change theories and involving stakeholders in intervention design may increase the likelihood of success. The under-utilisation of comprehensive co-design methods presents an opportunity to ensure that personalisation approaches better meet the needs of target populations. Moreover, future digital interventions should address both behaviour change and food environment influences on vegetable intake.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

Social media platforms may be promising intervention tools to address the nutrition literacy and associated health behaviours of young women. We aimed to co-design a lifestyle intervention on social media targeting eating, physical activity, and social wellbeing that is evidence-based, acceptable, and engaging for young women aged 18–24 years. The study used a participatory design framework and previously published iterative mixed methods approach to intervention development. Matrices for workshop objectives were constructed using expert discussions and insights were sought from young women in participatory workshops. A 10-step qualitative data analysis process resulted in relevant themes, which guided intervention development. The resulting intervention, the Daily Health Coach, uses multiple features of Instagram to disseminate health information. Co-created nutrition content considers themes such as holism, food relationships, and food neutrality and acknowledges commonly experienced barriers associated with social media use such as nutrition confusion, body image concerns, and harmful comparison. This study may guide other researchers or health professionals seeking to engage young women in the co-design of women’s health promotion or intervention content on social media.

Abstract Background Adolescence presents a window of opportunity to establish good nutrition and physical activity behaviours to carry throughout the life course. Adolescents are at risk of developing cardiovascular and other chronic diseases due to poor the complex interplay of physical and mental health lifestyle risk factors. Text messaging is adolescents main form of everyday communication and text message programs offer a potential solution for support and improvement of lifestyle health behaviours. The primary aim of this study is to determine effectiveness of the Health4Me text message program to improve adolescent’s physical activity or nutrition behaviours among adolescents over 6-months, compared to usual care. Methods Health4Me is a virtual, two-arm, single-blind randomised controlled trial, delivering a 6-month healthy lifestyle text message program with optional health counselling. Recruitment will be through digital advertising and primary care services. In total, 390 adolescents will be randomised 1:1 to intervention or control (usual care) groups. The intervention group will receive 4–5 text messages per week for 6-months. All text messages have been co-designed with adolescents. Messages promote a healthy lifestyle by providing practical information, health tips, motivation and support for behaviour change for physical activity, nutrition, mental health, body image, popular digital media and climate and planetary health. Virtual assessments will occur at baseline and 6-months assessing physical health (physical activity, nutrition, body mass index, sleep), mental health (quality of life, self-efficacy, psychological distress, anxiety, depression, eating disorder risk) and lifestyle outcomes (food insecurity and eHealth literacy). Discussion This study will determine the effectiveness of a 6-month healthy lifestyle text message intervention to improve physical activity and nutrition outcomes in adolescents. Trial registration Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622000949785 , Date registered: 05/07/2022.

BackgroundCOVID-19 lockdowns caused widespread closures of supportive care services for breast cancer survivors in Australia. In a randomized controlled trial, our team’s lifestyle-focused, evidence-based SMS text message support program (EMPOWER-SMS COVID-19) was found to be acceptable and useful for breast cancer survivors, and it was ready for rapid widespread delivery. ObjectiveThis study aims to evaluate the reach (uptake) of an adapted 3-month lifestyle-focused SMS text message program (EMPOWER-SMS COVID-19) and barriers and enablers to implementation using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. MethodsA mixed methods pre-post study was conducted to evaluate the EMPOWER-SMS COVID-19 program. The study evaluated the following aspects: (1) reach/representativeness, which refers to the proportion of participant enrollment (ie, number enrolled/number that visited the study website) and demographics (eg, age, sex, ethnicity, time since completing treatment, Index of Relative Socio-economic Advantage and Disadvantage [IRSAD; quintile 1, which refers to most disadvantaged areas, to quintile 5, which refers to least disadvantaged areas, and remoteness); (2) effectiveness, in which participant engagement and acceptability were evaluated using SMS text message reply data and a feedback survey (5-point Likert scale and free-text responses); (3) adoption, which corresponds to the proportion of organizations or health professionals who agreed to promote the program; (4) implementation fidelity and maintenance, which evaluated SMS text message delivery data, opt-outs, costs, and adaptations. Quantitative data were summarized using means and SDs or frequencies and percentages, while qualitative data were analyzed thematically. ResultsWith regard to the reach/representativeness of the program, 841/1340 (62.8%) participants enrolled and provided electronic consent. Participants had a mean age of 58.8 (SD 9.8; range 30-87) years. According to the data collected, most participants identified as female (837/840, 99.6%) and White (736/840, 87.6%) and nearly half (418/841, 49.7%) finished treatment ≤18 months ago. Most resided in major cities (574/838, 68.5%) and 30% (251/838) in IRSAD quintile 1 or 2. In terms of effectiveness, 852 replies were received from 511 unique participants (median 1; range 1-26). The most common replies were participants stating how they heard about the program (467/852, 54.8%) or “thank you” (131/852, 15.4%). None of the replies contained urgent safety concerns. Among participants who provided feedback (449/841, 53.4%), most “(strongly) agreed” the SMS text messages were easy to understand (445/448, 99.3%), useful (373/440, 84.8%), helped participants feel supported (388/448, 86.6%), and motivated participants to be physically active (312/445, 70.1%) and eat healthier (313/457, 68.5%). Free-text responses revealed 5 factors influencing engagement: (1) feeling supported and less alone, (2) motivation and reassurance for health self-management, (3) the variety of information, (4) weblinks to information and resources, and (5) the option to save the SMS text messages. Concerning adoption, 50% (18/36) of organizations/health professionals agreed to promote the program. With regard to implementation/maintenance, SMS text messages were delivered as planned (97.43% [41,257/42,344] of SMS text messages were successfully delivered) with minimal opt-outs (62/838, 7.4%) and low cost (Aus $15.40/participant; Aus $1=US $0.67). No adaptations were made during the intervention period. Postintervention adaptations included adding weblinks and participant-selected customizations. ConclusionsEMPOWER-SMS COVID-19 was implemented quickly, had a broad reach, and had high engagement and acceptability among socioeconomically diverse participants. The program had high fidelity, low cost, and required minimal staff oversight, which may facilitate future implementation. However, further research is needed to evaluate barriers and enablers to adoption and implementation for health professionals and strategies for long-term maintenance.

BackgroundReducing lifestyle risk behaviors among adolescents depends on access to age-appropriate health promotion information. Chatbots—computer programs designed to simulate conversations with human users—have the potential to deliver health information to adolescents to improve their lifestyle behaviors and support behavior change, but research on the feasibility and acceptability of chatbots in the adolescent population is unknown. ObjectiveThis systematic scoping review aims to evaluate the feasibility and acceptability of chatbots in nutrition and physical activity interventions among adolescents. A secondary aim is to consult adolescents to identify features of chatbots that are acceptable and feasible. MethodsWe searched 6 electronic databases from March to April 2022 (MEDLINE, Embase, Joanna Briggs Institute, the Cumulative Index to Nursing and Allied Health, the Association for Computing Machinery library, and the IT database Institute of Electrical and Electronics Engineers). Peer-reviewed studies were included that were conducted in the adolescent population (10-19 years old) without any chronic disease, except obesity or type 2 diabetes, and assessed chatbots used nutrition or physical activity interventions or both that encouraged individuals to meet dietary or physical activity guidelines and support positive behavior change. Studies were screened by 2 independent reviewers, with any queries resolved by a third reviewer. Data were extracted into tables and collated in a narrative summary. Gray literature searches were also undertaken. Results of the scoping review were presented to a diverse youth advisory group (N=16, 13-18 years old) to gain insights into this topic beyond what is published in the literature. ResultsThe search identified 5558 papers, with 5 (0.1%) studies describing 5 chatbots meeting the inclusion criteria. The 5 chatbots were supported by mobile apps using a combination of the following features: personalized feedback, conversational agents, gamification, and monitoring of behavior change. Of the 5 studies, 2 (40.0%) studies focused on nutrition, 2 (40.0%) studies focused on physical activity, and 1 (20.0%) focused on both nutrition and physical activity. Feasibility and acceptability varied across the 5 studies, with usage rates above 50% in 3 (60.0%) studies. In addition, 3 (60.0%) studies reported health-related outcomes, with only 1 (20.0%) study showing promising effects of the intervention. Adolescents presented novel concerns around the use of chatbots in nutrition and physical activity interventions, including ethical concerns and the use of false or misleading information. ConclusionsLimited research is available on chatbots in adolescent nutrition and physical activity interventions, finding insufficient evidence on the acceptability and feasibility of chatbots in the adolescent population. Similarly, adolescent consultation identified issues in the design features that have not been mentioned in the published literature. Therefore, chatbot codesign with adolescents may help ensure that such technology is feasible and acceptable to an adolescent population.

There is growing recognition that young people should be given opportunities to participate in the decisions that affect their lives, such as advisory groups, representative councils, advocacy or activism. Positive youth development theory and sociopolitical development theory propose pathways through which youth participation can influence mental health and wellbeing outcomes. However, there is limited empirical research synthesising the impact of participation on youth mental health and/or wellbeing, or the characteristics of activities that are associated with better or worse mental health and/or wellbeing outcomes. This scoping review seeks to address this gap by investigating the scope and nature of evidence detailing how youth participation initiatives can influence mental health and/or wellbeing outcomes for participants. To be eligible, literature must describe youth (aged 15-24) in participation activities and the impact of this engagement on participant mental health and/or wellbeing outcomes. A systematic scoping review of peer-reviewed and grey literature will be conducted using Scopus, PsycINFO, Embase, Medline and grey literature databases. The scoping review will apply established methodology by Arksey and O'Malley, Levac and colleagues and the Joanna Briggs Institute. Title, abstract, and full text screening will be completed by two reviewers, data will be extracted by one reviewer. Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), including a qualitative summary of the characteristics of youth participation and their influence on youth mental health outcomes. Youth advisory group members will be invited to deliver governance on the project from the outset; participate in, and contribute to, all stages of the review process; reflect on their own experiences of participation; and co-author the resulting publication. This scoping review will provide essential knowledge on how participation activities can be better designed to maximise beneficial psychosocial outcomes for involved youth.

BackgroundDigital health interventions, including apps and web-based services, are on the rise due to their facilitated access to target groups. The constant evolution of technology calls for participatory research methodologies to understand youth expectations and the use of technology. The creative and collaborative nature of co-design allows for the active integration of youth desires and may enhance acceptability when it comes to digital health tools. ObjectiveThe primary objective of this review is to assess the breadth of literature on digital health interventions that have been co-designed for and by young adults, including the types of available evidence, the identification of key characteristics relevant to young adult co-design, and the examination of research conduct in this space. MethodsThe proposed scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) Manual for Scoping Reviews. As well as the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist for reporting scoping reviews, an adaptation of Arksey and O’Malley’s 6-stage framework for scoping reviews will be referenced. Peer-reviewed primary research, where young adults (aged 15-35 years) were actively involved in the design and development process of digital health interventions, will be collated for analyses. Five databases, including MEDLINE (Ovid), Cochrane, CINAHL Plus, Google Scholar, and Scopus, will be searched for relevant papers. Search strategies will be comprehensive to identify both published and unpublished literature. Relevant gray literature and secondary research will be excluded but pooled for separate analysis and citation chaining. Results will be presented in one or multiple forms, including narrative, tabular, or diagrammatic. ResultsData collection commenced in October 2021. Following data extraction according to the JBI results extraction instrument and independent quality assurance of included studies, a narrative synthesis of each paper included in the final pool will allow for data charting. As of May 2022, 19 papers are included for analysis. We expect the results to be published by autumn 2022. ConclusionsThis protocol provides guidance for researchers who plan to conduct a similar style of investigation and promotes standardization of the scoping review process. We anticipate the provision of an overview of participatory digital health research involving young adults, highlighting any gaps in this research area, as well as potential areas for further study. International Registered Report Identifier (IRRID)DERR1-10.2196/38635

Adolescence and young adulthood (AYA) are formative life stages, second only to the first 1000 days. Yet young people have historically been ‘forgotten’ in our health system. Major health risk factors, like adolescent obesity, have largely been left untreated, resulting in significant chronic disease burdens and health costs later in life. In Australia, strategies to address obesity have primarily been implemented disjointedly by different jurisdictions of government, which has meant that obesity responses across the country have been piecemeal. Current state-based interventions show modest effects on improving weight-related behaviours. Major fiscal and regulatory measures have yet to be implemented despite demonstrable public health benefits and public support. The new National obesity strategy 2022–2032, which recognises the importance of engaging with youth, is a welcomed approach to coordinating obesity prevention Australia-wide. The challenge remains to ensure that meaningful AYA engagement is followed through with future interventions. The digitalisation of society poses future health challenges for AYA because of the likelihood of greater physical inactivity and ease of access to junk foods.

ABSTRACT The global epidemiology of multidrug resistant Klebsiella pneumoniae, a serious threat to both animal and human health, is dominated by the spread of pathogenic clones, each separately evolving via acquisition of transferable antibiotic resistance or niche-specific virulence determinants. In horses, K. pneumoniae infection can lead to severe respiratory illness. Here, we characterized multiple isolates recovered from bronchial aspirates of a mare with pneumonia refractory to antibiotics. First, we used a combination of standard microbiology, bacteriophage cross-susceptibility and antibiotic resistance testing to profile the infecting K. pneumoniae population. The genomes of isolates with distinct fingerprints (pulsed-field gel electrophoresis) and unique combined bacteriophage/antibiotic profiles were then further analyzed using whole-genome sequencing. Adhesion to human epithelial cells and biofilm production were also measured as virulence indicators. Although it is commonly expected for one clone to dominate an infection episode, we identified five coexisting multidrug resistant K. pneumoniae sharing the same niche. One was a novel sequence type (ST4656), while the other four were all members of emerging human pathogenic clonal groups (ST307, ST628, ST893 and ST392). These isolates did not display significant differences from one another in terms of virulence or resistance and differed only in plasmid content from isolates implicated in severe human infections, with equal potential to prolong duration and severity of infection when sharing the same niche. This study highlights the importance of more precise surveillance and detection measures to uncover bacterial heterogeneity, reminding us that the “single clone” concept is not an absolute in invasive bacterial infections. IMPORTANCE Multidrug resistant Klebsiella pneumoniae are agents of life-threatening infections in animals and humans, with several multidrug resistant clones causing outbreaks of disease worldwide. It is generally accepted that only one clone will be dominant in an infection episode. In this study, we investigated K. pneumoniae isolates from a horse with severe pneumonia and demonstrated co-occurrence of multiple sequence types previously identified as emerging human pathogens. The equine isolates are not significantly different from one another in terms of virulence or resistance, with equal potential to prolong duration and severity of infection, and are indistinguishable from isolates recovered from humans, except for plasmid content. Our study highlights how the “one dominant clone” concept is not an absolute in severe infection, illustrating the need for improved diagnostics to track heterogeneity of infection, and reinforces the importance of cross-monitoring of environmental and human reservoirs of multidrug resistant pathogens.

Abstract Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no β-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.

Online food delivery usage has soared during the 2019 novel coronavirus (COVID-19) pandemic which has seen increased demand for home-delivery during government mandated stay-at-home periods. Resulting implications from COVID-19 may threaten decades of development gains. It is becoming increasingly more important for the global community to progress toward sustainable development and improve the wellbeing of people, economies, societies, and the planet. In this perspective article, we discuss how the rising use of these platform-to-consumer delivery operations may impede advances toward the United Nations 2030 Sustainable Development Goals (SDGs). Specifically, online food delivery services may disrupt SDGs that address good health and wellbeing, responsible consumption and production, climate action and decent work and economic growth. To mitigate potential negative impacts of these meal delivery apps, we have proposed a research and policy agenda that is aligned with entry points within a systems approach identified by the World Health Organization. Food industry reforms, synergised public health messaging and continuous monitoring of the growing impact of online food delivery should be considered for further investigation by researchers, food industry, governments, and policy makers.

Global wildlife populations are in decline, in part, due to urbanization. However, in urban landscapes, green infrastructure such as green roofs are being created to provide habitat for wildlife. Green roof isolation, planting heterogeneity, and size can all influence wildlife biodiversity, as may the age of a green roof. When new habitat is created, wildlife use of these new habitats is expected to increase over time. To test this expectation for birds, we monitored bird activity prior to and after installation of small green roof plots on six buildings located within New York City parks. Contrary to expectations, bird activity and bird species richness did not increase after green roof plot installation, nor did they increase over a period of 4 years following installation. These unexpected results may reflect the relatively small size of the plots or the fact that the plots were on buildings located within urban parks. Bird activity and bird species richness varied widely between roofs, and the composition of rooftop bird species may have been more influenced by the characteristics of the surrounding landscapes than the presence of the green roof plots. These findings suggest that small urban green roofs within a larger and, potentially, higher quality habitat may not provide additional habitat for foraging birds. Urban green roofs have numerous ecological and environmental benefits, but the size and characteristics of landscapes surrounding a green roof need to be considered when installing green roofs as wildlife habitat.

Abstract Background Knowledge translation (KT) platforms are organisations, initiatives and networks that focus on supporting evidence-informed policy-making at least in part about the health-system arrangements that determine whether the right programmes, services and products get to those who need them. Many descriptions and evaluations of KT platforms in low- and middle-income countries have been produced but, to date, they have not been systematically reviewed. Methods We identified potentially relevant studies through a search of five electronic databases and a variety of approaches to identify grey literature. We used four criteria to select eligible empirical studies. We extracted data about seven characteristics of included studies and about key findings. We used explicit criteria to assess study quality. In synthesising the findings, we gave greater attention to themes that emerged from multiple studies, higher-quality studies and different contexts. Results Country was the most common jurisdictional focus of KT platforms, EVIPNet the most common name and high turnover among staff a common infrastructural feature. Evidence briefs and deliberative dialogues were the activities/outputs that were the most extensively studied and viewed as helpful, while rapid evidence services were the next most studied but only in a single jurisdiction. None of the summative evaluations used a pre–post design or a control group and, with the exception of the evaluations of the influence of briefs and dialogues on intentions to act, none of the evaluations achieved a high quality score. Conclusions A large and growing volume of research evidence suggests that KT platforms offer promise in supporting evidence-informed policy-making in low- and middle-income countries. KT platforms should consider as next steps expanding their current, relatively limited portfolio of activities and outputs, building bridges to complementary groups, and planning for evaluations that examine ‘what works’ for ‘what types of issues’ in ‘what types of contexts’.

BackgroundAdolescence is a critical life stage characterized by an interplay of biological, social, and environmental factors. Such factors influence lifestyle health-related trajectories, including dietary behaviors, physical activity levels, body weight, and sleep. Generation Z (born 1995-2015) is the most internet-dependent and technologically savvy generation in history with increasing rates of smartphone ownership across high- and low-income countries. Gaps exist in understanding what online platforms adolescents are using and barriers and facilitators of these platforms to seek lifestyle health information. ObjectiveWe evaluated adolescents’ perceptions on the use of contemporary digital platforms (websites, social media platforms, smartphone apps) to seek lifestyle heath information or advice. MethodsVirtual focus groups were held via Zoom teleconference between July 2021 and August 2021. Eligible participants were 13 years to 18 years old, were living in Australia, and had searched for online lifestyle health information in the previous 3 months. For this study, lifestyle health information referred to key behaviors and risk factors for chronic disease, namely, diet, physical activity, weight management, and sleep. Participants were recruited through an existing database of research participants and networks of the research team. Focus groups were analyzed using the framework approach, in which data are systematically searched to recognize patterns in the data and manage, analyze, and identify themes. Focus group audio files were transcribed verbatim and independently coded by 2 researchers (RR, SSJ). Through an iterative, reflexive process, a final coding matrix was agreed on by all researchers and used to thematically analyze the data. ResultsWe held 5 focus groups (n=32; mean age: 16.3 [SD 1.4] years; 18/32, 56% female; 13/32, 41% spoke language other than English at home). Thematic analysis revealed participants searched for information both actively (eg, on Google or YouTube) and passively (eg, scrolling social media and using existing apps preloaded to their smartphone such as Apple Health, Samsung Health, or Google Fit apps). Participants identified that the most helpful information was well-presented in terms of aesthetic appeal and layout and came from a credible and reliable source (eg, any sponsorships disclosed), and they expressed the need for the information to be relatable. Mixed views were reported for the application of lifestyle health information found online. Some participants reported behavior change, while others noted that certain advice was hard to maintain and incorporate into their lifestyle. ConclusionsThis study highlights the abundance and complexity of lifestyle health information online for adolescents. Adolescents in the digital age seek access to information that is appealing, credible, relevant, and actionable for lifestyle health behaviors. To appeal to needs of adolescents, future interventions for adolescents relating to lifestyle health must consider co-design methodological approaches. Furthermore, the regulation of lifestyle health information available online warrants further investigation.

Background: Traditionally, adolescent participation in research has been tokenistic. Adolescents are rarely afforded the opportunity to influence decision-making in research designed to prevent obesity. Engaging adolescents in meaningful decision-making may enhance research translation. This review aimed to analyze the current modes and nature of adolescent participation in obesity prevention research decision-making.Methods: A systematic scoping review was conducted using Arksey and O'Malley's six-stage framework. Six major databases were searched for peer-reviewed primary research studies with adolescent participation related to obesity, physical activity, and diet. Modes of adolescent participation were categorized based on the Lansdown-UNICEF conceptual framework for measuring outcomes of adolescent participation. The framework outlines three modes of meaningful participation: (i) consultative, which involves taking opinions and needs into consideration; (ii) collaborative, where adolescents are partners in the decision-making process; and (iii) adolescent-led participation where adolescents have the capacity to influence the process and outcomes. The degree of involvement in research cycles was classified based on the National Health and Medical Research Council consumer engagement framework. Five stages of the research cycle were determined: identify, design and develop, conduct, analyze and disseminate.Results: In total, 126 papers describing 71 unique studies were identified. Of these, 69% (49/71) took place in the USA, and 85% (52/61) were conducted in minority or underserved communities, while males were more likely to be under-represented. In 49% (35/71) of studies, participation was consultative and 9% (6/71) of studies involved an adolescent-led approach. Furthermore, 87% (62/71) of studies incorporated adolescent participation in one or more of the research cycle's formative phases, which involve eliciting views, opinions and idea generation. Only 11% of studies engaged adolescents in all five stages of the research cycle where adolescents could have more influence over the research process.Conclusion: Meaningful adolescent participation in the obesity prevention research cycle is limited. Empowering and mobilizing equal partnership with adolescents should be at the forefront of all adolescent-related obesity prevention research.

BackgroundSupporting healthy lifestyle changes is a key aim of cardiovascular and pulmonary rehabilitation programs. SMS text messaging programs have demonstrated effectiveness in cardiovascular disease risk reduction, weight loss, increasing physical activity, and smoking cessation. The optimization of SMS text messaging programs may deliver greater population benefits as mobile phone use becomes ubiquitous. Visual messaging (ie, image-based messages) has the potential to communicate health messages via digital technology and result in enhanced engagement. ObjectiveThis study aims to determine and understand patient preferences for lifestyle-focused visual text messages that support cardiovascular and pulmonary rehabilitation. MethodsA discrete choice experiment was conducted in a 4-stage iterative process to elicit patient preferences for visual message features. Attribute and level development yielded 3 attributes (purpose, image type, and web address), and 16 choice sets were subsequently constructed according to a full factorial design. Patients participating in cardiovascular and pulmonary rehabilitation were surveyed (on the web) for their preferences regarding the visual message choice sets. Respondents were asked to choose among 16 pairs of visual messages regarding key lifestyle behaviors, namely, physical activity and nutrition. The data were analyzed using a conditional logit model. ResultsThere was a total of 1728 observations from 54 unique respondents. Two factors that were associated with patient preference were gain-framed purpose compared with no purpose (odds ratio [OR] 1.93, 95% CI 1.40-2.65) and real images compared with cartoon images (OR 1.26, 95% CI 1.04-1.54). A loss-framed purpose was less preferred than no purpose (OR 0.55, 95% CI 0.42-0.74). Overall, patients preferred positive images that were colorful and engaged with text that supported the image and had a preference for images of real people rather than cartoons. ConclusionsA discrete choice experiment is a scientific method for eliciting patient preferences for a visual messaging intervention that is designed to support changes in lifestyle behaviors. SMS text messaging programs that use visual aids may result in greater patient satisfaction by using a gain frame, using real images, and avoiding a loss frame. Further research is needed to explore the feasibility of implementation and the health and behavioral outcomes associated with such visual messaging programs.

Abstract An article published in Microbiome in July 2018 uses incorrect definitions of integron integrase IntI1 and of class 1 integrons that affect the interpretation of the data.

Online food delivery (OFD) platforms have become increasingly popular due to advanced technology, which is changing the way consumers purchase food prepared outside of the home. There is limited research investigating the healthiness of the digital food environment and its influence on consumer choice and dietary behaviours. This study is the first to examine the nutritional quality and marketing attributes of menu items from popular independent and franchise restaurants and takeaway outlets on New Zealand’s market leading OFD platform (UberEATS®). A total of 374 popular independent and franchise restaurants and takeaway outlets were identified to form a database of complete menus and marketing attributes. All 25,877 menu items were classified into 38 food and beverage categories based on the Australian Dietary Guidelines. Of complete menus, 73.3% (18,955/25,877) were discretionary. Thirty-six percent (9419/25,877) were discretionary cereal-based mixed meals, the largest of the 38 categories. Discretionary menu items were more likely to be categorized as most popular (OR: 2.0, 95% CI 1.7–2.2), accompanied by a photo (OR: 1.7, 95% CI 1.6–1.8), and offered as a value bundle (OR: 4.6, 95% CI 3.2–6.8). Two of the three discretionary mixed meal categories were significantly less expensive than their healthier counterparts (p < 0.001). The overwhelming availability and promotion of discretionary choices offered by restaurants and takeaway outlets on OFD platforms have implications for public health policy. Further research to explore direct associations between nutritional quality and consumers’ dietary choices is required.

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is performed to diagnose and manage conditions of the biliary and pancreatic ducts. Though effective, it is associated with common adverse events (AEs). The purpose of this study is to systematically review ERCP AE rates and report up-to-date pooled estimates.Methods and analysis A comprehensive electronic search will be conducted of relevant medical databases through 10 November 2020. A study team of eight data abstracters will independently determine study eligibility, assess quality and abstract data in parallel, with any two concordant entries constituting agreement and with discrepancies resolved by consensus. The primary outcome will be the pooled incidence of post-ERCP pancreatitis, with secondary outcomes including post-ERCP bleeding, cholangitis, perforation, cholecystitis, death and unplanned healthcare encounters. Secondary outcomes will also include rates of specific and overall AEs within clinically relevant subgroups determined a priori. DerSimonian and Laird random effects models will be used to perform meta-analyses of these outcomes. Sources of heterogeneity will be explored via meta-regression. Subgroup analyses based on median dates of data collection across studies will be performed to determine whether AE rates have changed over time.Ethics and dissemination Ethics approval is not required for this study as it is a planned meta-analysis of previously published data. Participant consent is similarly not required. Dissemination is planned via presentation at relevant conferences in addition to publication in peer-reviewed journals.PROSPERO registration numberCRD42020220221.

BackgroundBreast cancer is the most common cancer among women globally. Recovery from breast cancer treatment can be mentally and physically challenging. SMS text message programs offer a novel way to provide health information and support, but few programs are co-designed with consumer representatives. ObjectiveThis study aims to report the procedures and outcomes of a co-design process of a lifestyle-focused SMS text message program to support women’s mental and physical health after breast cancer treatment. MethodsWe followed an iterative mixed methods two-step process: (1) co-design workshop with consumers and health professionals and researchers to draft text messages and (2) evaluation of message content, which was scored (5-point Likert scale; 1=strongly disagree to 5=strongly agree) for ease of understanding, usefulness, and appropriateness, and readability (Flesch-Kincaid score). Additional free-text responses and semistructured interviews were coded into themes. Messages were edited or deleted based on the evaluations, with consumers’ evaluations prioritized. ResultsIn step 1, co-designed text messages (N=189) were semipersonalized, and the main content themes were (1) physical activity and healthy eating, (2) medications and side effects, (3) mental health, and (4) general breast cancer information. In step 2, consumers (n=14) and health professionals and researchers (n=14) provided 870 reviews of 189 messages and found that most messages were easy to understand (799/870, 91.8%), useful (746/870, 85.7%), and appropriate (732/870, 84.1%). However, consumers rated 50 messages differently from health professionals and researchers. On the basis of evaluations, 37.6% (71/189) of messages were deleted, 36.5% (69/189) were edited, and 12 new messages related to fatigue, self-care, and cognition were created. The final 130 text messages had a mean 7.12 (SD 2.8) Flesch-Kincaid grade level and 68.9 (SD 15.5) ease-of-reading score, which represents standard reading ease. ConclusionsCo-designing and evaluating a bank of evidence-based mental and physical health-themed text messages with breast cancer survivors, health professionals, and researchers was feasible and resulted in a bank of 130 text messages evaluated highly by participants. Some consumer evaluations differed from health professionals and researchers, supporting the importance of co-design.

Abstract Background Breast cancer is the most common cancer diagnosed in women worldwide. In developed countries, 80–90% of women will survive five years after diagnosis but the transition from hospital-based care to health self-management and self-efficacy can be difficult. Text messaging programs offer a simple and proven way to provide support to people with chronic diseases. This study aims to test the effectiveness of a text message support program at improving women’s health self-efficacy, and physical and mental health outcomes after breast cancer treatments compared to usual care at 6-months and to understand the barriers and enablers to widespread implementation. Methods Single-blind randomised control trial (RCT; N = 160) comparing a text message support intervention to usual care in women with breast cancer (recruited from a large tertiary referral hospital in Sydney, Australia). The intervention group will receive a six-month text message support program, which consists of semi-personalised, supportive, lifestyle-focused text messages (4 messages/week) in addition to usual care. The control group will receive usual care without the text message program. Outcomes will be assessed at 6-months. The primary outcome is change in self-efficacy for managing chronic disease. Secondary outcomes include change in clinical outcomes (body mass index), lifestyle outcomes (physical activity levels, dietary behaviours), mood (depression and anxiety scales), quality of life, satisfaction with, and usefulness of the intervention. Analyses will be performed on the principle of intention-to-treat to examine differences between intervention and control groups. Discussion This study will test if a scalable and cost-effective text-messaging intervention is effective at improving women’s health self-efficacy, as well as physical and mental health outcomes. Moreover, this study will provide essential preliminary data to bolster a large multicentre RCT to helpsupport breast cancer survivors throughout recovery and beyond. Trial registration Australia New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12618002020268, 17 December 2018

ABSTRACTHorizontal transfer of plasmids plays a pivotal role in dissemination of antibiotic resistance genes and emergence of multidrug-resistant bacteria. Plasmid sequencing is thus paramount for accurate epidemiological tracking in hospitals and routine surveillance. Combining Nanopore and Illumina sequencing allowed full assembly of a carbapenemase-encoding megaplasmid carried by multidrug-resistant clinical isolate FFUP_PS_41. Average nucleotide identity analyses revealed that FFUP_PS_41 belongs to the recently proposed new species Pseudomonas shirazica, related to the P. putida phylogenetic group. FFUP_PS_41 harbours a 498,516-bp megaplasmid (pJBCL41) with limited similarity to publicly-available plasmids. pJBCL41 contains genes predicted to encode replication, conjugation, partitioning and maintenance functions and heavy metal resistance. The |aacA7|blaVIM-2|aacA4| cassette array (resistance to carbapenems and aminoglycosides) is located within a class 1 integron that is a defective Tn402 derivative. This transposon lies within a 50,273-bp region bound by Tn3-family 38-bp inverted repeats and flanked by 5-bp direct repeats (DR) that composes additional transposon fragments, five insertion sequences and a Tn3-Derived Inverted-Repeat Miniature Element. The hybrid Nanopore/Illumina approach allowed full resolution of a carbapenemase-encoding megaplasmid from P. shirazica. Identification of novel megaplasmids sheds new light on the evolutionary effects of gene transfer and the selective forces driving antibiotic resistance.

Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood–brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms. We hypothesized that H-FIRE mediated BBB disruption (BBBD) occurs via cytoskeletal remodeling and alterations in tight junction (TJ) protein regulation. Intracranial H-FIRE was delivered to Fischer rats prior to sacrifice at 1-, 24-, 48-, 72-, and 96 h post-treatment. Cytoskeletal proteins and native and ubiquitinated TJ proteins (TJP) were evaluated using immunoprecipitation, Western blotting, and gene-expression arrays on treated and sham control brain lysates. Cytoskeletal and TJ protein expression were further evaluated with immunofluorescent microscopy. A decrease in the F/G-actin ratio, decreased TJP concentrations, and increased ubiquitination of TJP were observed 1–48 h post-H-FIRE compared to sham controls. By 72–96 h, cytoskeletal and TJP expression recovered to pretreatment levels, temporally corresponding with increased claudin-5 and zonula occludens-1 gene expression. Ingenuity pathway analysis revealed significant dysregulation of claudin genes, centered around claudin-6 in H-FIRE treated rats. In conclusion, H-FIRE is capable of permeating the BBB in a spatiotemporal manner via cytoskeletal-mediated TJP modulation. This minimally invasive technology presents with applications for localized and long-lived enhanced intracranial drug delivery.

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.

In this letter, we present the performance of a 100 μm × 400 μm × 40 nm W Transition-Edge Sensor with a critical temperature of 40 mK. This device has a noise equivalent power of 1.5×10-18 W/Hz, in a bandwidth of 2.6 kHz, indicating a resolution for Dirac delta energy depositions of 40 ± 5 meV (rms). The performance demonstrated by this device is a critical step toward developing a O(100) meV threshold athermal phonon detector for low-mass dark matter searches.

ABSTRACT Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no plasmid-mediated RND efflux pump gene cluster has yet been found to confer resistance to tigecycline. Here, we identified a novel RND efflux pump gene cluster, designated tmexCD1-toprJ1, on plasmids from five pandrug-resistant Klebsiella pneumoniae isolates of animal origin. TMexCD1-TOprJ1 increased (by 4- to 32-fold) the MICs of tetracyclines (including tigecycline and eravacycline), quinolones, cephalosporins, and aminoglycosides for K. pneumoniae, Escherichia coli, and Salmonella. TMexCD1-TOprJ1 is closely related (64.5% to 77.8% amino acid identity) to the MexCD-OprJ efflux pump encoded on the chromosome of Pseudomonas aeruginosa. In an IncFIA plasmid, pHNAH8I, the tmexCD1-toprJ1 gene cluster lies adjacent to two genes encoding site-specific integrases, which may have been responsible for its acquisition. Expression of TMexCD1-TOprJ1 in E. coli resulted in increased tigecycline efflux and in K. pneumoniae negated the efficacy of tigecycline in an in vivo infection model. Expression of TMexCD1-TOprJ1 reduced the growth of E. coli and Salmonella but not K. pneumoniae. tmexCD1-toprJ1-positive Enterobacteriaceae isolates were rare in humans (0.08%) but more common in chicken fecal (14.3%) and retail meat (3.4%) samples. Plasmid-borne tmexCD1-toprJ1-like gene clusters were identified in sequences in GenBank from Enterobacteriaceae and Pseudomonas strains from multiple continents. The possibility of further global dissemination of the tmexCD1-toprJ1 gene cluster and its analogues in Enterobacteriaceae via plasmids may be an important consideration for public health planning. IMPORTANCE In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae, the most problematic pathogens in human clinical settings—especially carbapenem-resistant K. pneumoniae. Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a “One Health” perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.

The role of portion control plates in achieving healthy diets is unclear. The aim of this scoping review was to systematically map findings from peer reviewed and grey literature to provide evidence for the use of portion control plates to promote healthy eating and nutrition-related knowledge in children and adults. A secondary aim was to review the design characteristics of portion control plates. The search was conducted in four databases, including Medline, CINAHL, Embase, and PsycInfo, and grey literature sources following the PRISMA scoping review guidelines. A total of 22 articles comprising 23 intervention studies and 8 from grey literature were included. It was found that the various two-dimensional and three-dimensional portion control plates examined were effective tools for better portion size selection in healthy children and adults. Most portion control plates dedicated half the plate to vegetables, a quarter to protein, and a quarter to carbohydrates. The use of portion control plates in nutrition interventions appears to promote weight loss among those with overweight and obesity and/or type 2 diabetes. However, portion control plates were mostly used as part of multicomponent interventions and the effectiveness of the portion control plate as a stand-alone educational resource or portion control tool alone was uncertain. Further interventional research is indicated to investigate portion plates as tools to improve dietary behaviours and food consumption at the population level.

This study aimed to explore the diagnostic accuracy of the Patient-Generated Subjective Global Assessment (PG-SGA) malnutrition risk screening tool when used to score patients based on their electronic medical records (EMR), compared to bedside screening interviews. In-patients at a rural health service were screened at the bedside (n = 50) using the PG-SGA, generating a bedside score. Clinical notes within EMRs were then independently screened by blinded researchers. The accuracy of the EMR score was assessed against the bedside score using area under the receiver operating curve (AUC), sensitivity, and specificity. Participants were 62% female and 32% had conditions associated with malnutrition, with a mean age of 70.6 years (SD 14.9). The EMR score had moderate diagnostic accuracy relative to PG-SGA bedside screen, AUC 0.74 (95% CI: 0.59–0.89). The accuracy, specificity and sensitivity of the EMR score was highest for patients with a score of 7, indicating EMR screen is more likely to detect patients at risk of malnutrition. This exploratory study showed that applying the PG-SGA screening tool to EMRs had enough sensitivity and specificity for identifying patients at risk of malnutrition to warrant further exploration in low-resource settings.

Abstract This study examines the impact of cefepime and APP-β (antipseudomonal penicillin/ β-lactamase inhibitor combinations) on Gram-negative bacterial colonization and resistance in two Australian ICUs. While resistance did not cumulatively increase, cefepime (but not APP-β treatment) was associated with acquisition of antibiotic resistant Enterobacteriaceae, consistent with an ecological effect. Analysis of the resident gut E. coli population in a subset of patients showed an increase in markers of horizontal gene transfer after cefepime exposure that helps explain the increase in APP-β resistance and reminds us that unmeasured impacts on the microbiome are key outcome determinants that need to be fully explored.

Abstract: Activated factor XIIa (FXIIa) is a serine protease that has received a great deal of interest in recent years as a potential target for the development of new antithrombotics. Despite the strong interest in obtaining structural information, only the structure of the FXIIa catalytic domain in its zymogen conformation is available. In this work, reproducible experimental conditions found for the crystallization of human plasma β-FXIIa and crystal growth optimization have led to determination of the first structure of the active form of the enzyme. Two crystal structures of human plasma β-FXIIa complexed with small molecule inhibitors are presented herein. The first is the noncovalent inhibitor benzamidine. The second is an aminoisoquinoline containing a boronic acid–reactive group that targets the catalytic serine. Both benzamidine and the aminoisoquinoline bind in a canonical fashion typical of synthetic serine protease inhibitors, and the protease domain adopts a typical chymotrypsin-like serine protease active conformation. This novel structural data explains the basis of the FXII activation, provides insights into the enzymatic properties of β-FXIIa, and is a great aid toward the further design of protease inhibitors for human FXIIa.

We identified discrete importation events of the mcr-1 gene on incompatibility group IncI2 plasmids in Escherichia coli isolated from patients in New South Wales, Australia, in 2011 and 2013. mcr-1 is present in a small minority of colistin-resistant Enterobacteriaceae and appears not to be established locally.