Systems analysis of innate and adaptive immunity in Long COVID.

Since the onset of the COVID-19 pandemic, significant progress has been made in developing effective preventive and therapeutic strategies against severe acute SARS-CoV-2 infection. However, the management of Long COVID (LC), an infection-associated chronic condition that has been estimated to affect 5-20% of individuals following SARS-CoV-2 infection, remains challenging due to our limited understanding of its mechanisms. Although LC is a heterogeneous disease that is likely to have several subtypes, immune system disturbances appear common across many cases. The extent to which these immune perturbations contribute to LC symptoms, however, is not entirely clear. Recent advancements in multi-omics technologies, capable of detailed, cell-level analysis, have provided valuable insights into the immune perturbations associated with LC. Although these studies are largely descriptive in nature, they are the crucial first step towards a deeper understanding of the condition and the immune system's role in its development, progression, and resolution. In this review, we summarize the current understanding of immune perturbations in LC, covering both innate and adaptive immune responses, and the cytokines and analytes involved. We explore whether these findings support or challenge the primary hypotheses about LC's underlying mechanisms. We also discuss the crosstalk between various immune system components and how it can be disrupted in LC. Finally, we emphasize the need for more tissue- and subtype-focused analyses of LC, and for enhanced collaborative efforts to analyze common specimens from large cohorts, including those undergoing therapeutic interventions. These collective efforts are vital to unravel the fundaments of this new disease, and could also shed light on the prevention and treatment of the larger family of chronic illnesses linked to other microbial infections.

Simulating institutional heterogeneity in sustainability science.

Sustainability outcomes are influenced by the laws and configurations of natural and engineered systems as well as activities in socio-economic systems. An important subset of human activity is the creation and implementation of institutions, formal and informal rules shaping a wide range of human behavior. Understanding these rules and codifying them in computational models can provide important missing insights into why systems function the way they do (static) as well as the pace and structure of transitions required to improve sustainability (dynamic). Here, we conduct a comparative synthesis of three modeling approaches- integrated assessment modeling, engineering-economic optimization, and agent-based modeling-with underexplored potential to represent institutions. We first perform modeling experiments on climate mitigation systems that represent specific aspects of heterogeneous institutions, including formal policies and institutional coordination, and informal attitudes and norms. We find measurable but uneven aggregate impacts, while more politically meaningful distributional impacts are large across various actors. Our results show that omitting institutions can influence the costs of climate mitigation and miss opportunities to leverage institutional forces to speed up emissions reduction. These experiments allow us to explore the capacity of each modeling approach to represent insitutions and to lay out a vision for the next frontier of endogenizing institutional change in sustainability science models. To bridge the gap between modeling, theories, and empirical evidence on social institutions, this research agenda calls for joint efforts between sustainability modelers who wish to explore and incorporate institutional detail, and social scientists studying the socio-political and economic foundations for sustainability transitions.

Systems approach for congruence and selection of cancer models towards precision medicine.

Cancer models are instrumental as a substitute for human studies and to expedite basic, translational, and clinical cancer research. For a given cancer type, a wide selection of models, such as cell lines, patient-derived xenografts, organoids and genetically modified murine models, are often available to researchers. However, how to quantify their congruence to human tumors and to select the most appropriate cancer model is a largely unsolved issue. Here, we present Congruence Analysis and Selection of CAncer Models (CASCAM), a statistical and machine learning framework for authenticating and selecting the most representative cancer models in a pathway-specific manner using transcriptomic data. CASCAM provides harmonization between human tumor and cancer model omics data, systematic congruence quantification, and pathway-based topological visualization to determine the most appropriate cancer model selection. The systems approach is presented using invasive lobular breast carcinoma (ILC) subtype and suggesting CAMA1 followed by UACC3133 as the most representative cell lines for ILC research. Two additional case studies for triple negative breast cancer (TNBC) and patient-derived xenograft/organoid (PDX/PDO) are further investigated. CASCAM is generalizable to any cancer subtype and will authenticate cancer models for faithful non-human preclinical research towards precision medicine.

Evaluating targeted COVID-19 vaccination strategies with agent-based modeling.

We evaluate approaches to vaccine distribution using an agent-based model of human activity and COVID-19 transmission calibrated to detailed trends in cases, hospitalizations, deaths, seroprevalence, and vaccine breakthrough infections in Florida, USA. We compare the incremental effectiveness for four different distribution strategies at four different levels of vaccine supply, starting in late 2020 through early 2022. Our analysis indicates that the best strategy to reduce severe outcomes would be to actively target high disease-risk individuals. This was true in every scenario, although the advantage was greatest for the intermediate vaccine availability assumptions and relatively modest compared to a simple mass vaccination approach under high vaccine availability. Ring vaccination, while generally the most effective strategy for reducing infections, ultimately proved least effective at preventing deaths. We also consider using age group as a practical surrogate measure for actual disease-risk targeting; this approach also outperforms both simple mass distribution and ring vaccination. We find that quantitative effectiveness of a strategy depends on whether effectiveness is assessed after the alpha, delta, or omicron wave. However, these differences in absolute benefit for the strategies do not change the ranking of their performance at preventing severe outcomes across vaccine availability assumptions.

Lessons Learned from Cross-Systems Approach to COVID-19 Pandemic Response in Juvenile Justice System, Colorado, USA.

The global COVID-19 pandemic illustrates the importance of a close partnership between public health and juvenile justice systems when responding to communicable diseases. Many setting-specific obstacles must be navigated to respond effectively to limit disease transmission and negative health outcomes while maintaining necessary services for youth in confinement facilities. The response requires multidisciplinary expertise and collaboration to address unique considerations. Public health mitigation strategies must balance the risk for disease against the negative effects of restrictions. Key aspects of the COVID-19 response in the juvenile justice system of Colorado, USA, involved establishing robust communication and data reporting infrastructures, building a multidisciplinary response team, adapting existing infection prevention guidelines, and focusing on a whole-person health approach to infection prevention. We examine lessons learned and offer recommendations on pandemic emergency response planning and managing a statewide public health emergency in youth confinement settings that ensure ongoing readiness.

Bridges and Mechanisms: Integrating Systems Science Thinking into Implementation Research.

We present a detailed argument for how to integrate, or bridge, systems science thinking and methods with implementation science. We start by showing how fundamental systems science principles of structure, dynamics, information, and utility are relevant for implementation science. Then we examine the need for implementation science to develop and apply richer theories of complex systems. This can be accomplished by emphasizing a causal mechanisms approach. Identifying causal mechanisms focuses on the "cogs and gears" of public health, clinical, and organizational interventions. A mechanisms approach focuses on how a specific strategy will produce the implementation outcome. We show how connecting systems science to implementation science opens new opportunities for examining and addressing social determinants of health and conducting equitable and ethical implementation research. Finally, we present case studies illustrating successful applications of systems science within implementation science in community health policy, tobacco control, health care access, and breast cancer screening.

Mind the implementation gap: a systems analysis of the NHS Long Term Workforce Plan to increase the number of doctors trained in the UK raises many questions.

BACKGROUND: The National Health Service (NHS) in England is facing a workforce crisis. A new Long Term Workforce Plan (LTWP) seeks to address this, setting out ambitious proposals to expand and reform domestic medical education and training in England. However, there are concerns about their feasibility. SOURCES OF DATA: In September 2023, over 60 individuals representing medical education and training in the UK participated in an exercise run by UK Medical Schools Council by using systems theory to identify risks. AREAS OF AGREEMENT: The UK does need more 'home grown' doctors, but the LTWP has important gaps, including lack of attention to postgraduate training, absence of reference to the need for more educators and capital investment and risk of inadequate clinical placement capacity, particularly in primary care settings. AREAS OF CONTROVERSY: There are unresolved differences in the understanding of a proposed medical apprenticeship model and no scheme has, as yet, been approved by the General Medical Council. Participants were unable to determine who the beneficiaries of this scheme will be (apart from the apprentices themselves). GROWING POINTS: While the LTWP represents a welcome, although overdue, commitment to address the NHS workforce crisis, we identified significant gaps that must be resolved. AREAS TIMELY FOR DEVELOPING RESEARCH: First, the development of the LTWP provides a case study that adds to literature on policymaking in the UK. Second, while we only examined the expansion of medical training, the method could be applied to other parts of the LTWP. Third, a prospective evaluation of its implementation is necessary.

Pillars of theoretical biology: "Biochemical systems analysis, I, II and III".

Michael Savageau's Biochemical Systems Analysis I, II, IIIpapers, published in volumes 25 and 26 of the journal,kickstarted a research programme that originated many of the core concepts and tools of Systems Biology. This article briefly summarizes these papers anddiscusses the most relevant developments in Biochemical Systems Theory since their publication.

Use of systems thinking and adapted group model building methods to understand patterns of technology use among older adults with type 1 diabetes: a preliminary process evaluation.

BACKGROUND: A growing number of older adults (ages 65+) live with Type 1 diabetes. Simultaneously, technologies such as continuous glucose monitoring (CGM) have become standard of care. There is thus a need to understand better the complex dynamics that promote use of CGM (and other care innovations) over time in this age group. Our aim was to adapt methods from systems thinking, specifically a participatory approach to system dynamics modeling called group model building (GMB), to model the complex experiences that may underlie different trajectories of CGM use among this population. Herein, we report on the feasibility, strengths, and limitations of this methodology. METHODS: We conducted a series of GMB workshops and validation interviews to collect data in the form of questionnaires, diagrams, and recordings of group discussion. Data were integrated into a conceptual diagram of the "system" of factors associated with uptake and use of CGM over time. We evaluate the feasibility of each aspect of the study, including the teaching of systems thinking to older adult participants. We collected participant feedback on positive aspects of their experiences and areas for improvement. RESULTS: We completed nine GMB workshops with older adults and their caregivers (N = 33). Each three-hour in-person workshop comprised: (1) questionnaires; (2) the GMB session, including both didactic components and structured activities; and (3) a brief focus group discussion. Within the GMB session, individual drawing activities proved to be the most challenging for participants, while group activities and discussion of relevant dynamics over time for illustrative (i.e., realistic but not real) patients yielded rich engagement and sufficient information for system diagramming. Study participants liked the opportunity to share experiences with peers, learning and enhancing their knowledge, peer support, age-specific discussions, the workshop pace and structure, and the systems thinking framework. Participants gave mixed feedback on the workshop duration. CONCLUSIONS: The study demonstrates preliminary feasibility, acceptability, and the value of GMB for engaging older adults about key determinants of complex health behaviors over time. To our knowledge, few studies have extended participatory systems science methods to older adult stakeholders. Future studies may utilize this methodology to inform novel approaches for supporting health across the lifespan.

Modelling the risk of Japanese encephalitis virus in Victoria, Australia, using an expert-systems approach.

Predictive models for vector-borne diseases (VBDs) are instrumental to understanding the potential geographic spread of VBDs and therefore serve as useful tools for public health decision-making. However, predicting the emergence of VBDs at the micro-, local, and regional levels presents challenges, as the importance of risk factors can vary spatially and temporally depending on climatic factors and vector and host abundance and preferences. We propose an expert-systems-based approach that uses an analytical hierarchy process (AHP) deployed within a geographic information system (GIS), to predict areas susceptible to the risk of Japanese encephalitis virus (JEV) emergence. This modelling approach produces risk maps, identifying micro-level risk areas with the potential for disease emergence. The results revealed that climatic conditions, especially the minimum temperature and precipitation required for JEV transmission, contributed to high-risk conditions developed during January and March of 2022 in Victora. Compared to historical climate records, the risk of JEV emergence was increased in most parts of the state due to climate. Importantly, the model accurately predicted 7 out of the 8 local government areas that reported JEV-positive cases during the outbreak of 2022 in Victorian piggeries. This underscores the model's potential as a reliable tool for supporting local risk assessments in the face of evolving climate change.

Tackling physical inactivity and inequalities: implementing a whole systems approach to transform community provision for disabled people and people with long-term health conditions.

BACKGROUND: Physical inactivity is a global public health priority. There are known health and well-being consequences of being inactive, and the benefits of being physically active are well established. However, there are persistent inequalities when it comes to how physically active people are, with disabled people, people living with long-term health conditions, and people residing in areas of socio-economic deprivation being particularly affected. Methods such as whole system approaches (WSAs), which are dynamic, multifaceted, and engage all relevant stakeholders, have gained momentum as an approach to address such complex public health problems. However, evidence relating to the implementation of WSAs to address physical inactivity is lacking. The aim of the Prevention and Enablement Model (PEM) was to take a whole system approach in Essex to encourage and support disabled people and/or individuals living with long-term health conditions to be more active, happier, and to live more independently. METHODS: The aim of this study was to explore the enablers, challenges, and reflections associated with the process of designing and implementing the PEM. Semi-structured interviews (n = 12) were used to collect data from people involved in the PEM's design, implementation and/or delivery. Data was analysed using Braun and Clarke's reflexive thematic analysis. RESULTS: Four themes were identified: (1) Working collaboratively: Specific enablers of time and space were identified as important in the planning and implementation of a WSA (2) Leadership and planning: Distributed and flexible leadership was identified as central to successful implementation (3) Re-orientating practice: Highlighted the transformative potential of a whole system approach and how it contrasts with conventional work practices, and (4) Reflection and learning: Informing ongoing refinements and further implementation of successful system change. CONCLUSIONS: These findings highlight the challenge and complexity of implementing a WSA that involves diverse stakeholders from across adult social care, the NHS, and the third sector. Several important enablers are identified, such as leadership and planning, and the challenges and discomfort that can arise whilst changing systems. Ongoing efforts are required to ensure that different elements of the system collaborate effectively to address inequalities in physical activity participation, through the implementation of a WSA.

Citizens' perspectives on healthy weight approaches in low SEP neighborhoods: a qualitative study from a systems perspective.

BACKGROUND: The physical and the social environment are important predictors of healthy weight, especially in low socioeconomic position (SEP) neighborhoods. Many Dutch municipalities have implemented a healthy weight approach (HWA). Yet, there is room for improvement. This system science study examined what influences the utilization of HWA facilities and activities, and what aspects can help to achieve a desired systems change (also called leverage point themes (LPTs)) in the HWA system as perceived by citizens living in low SEP neighborhoods. METHOD: All research phases were performed with four citizens co-researchers. Forty-seven citizens living in low SEP neighborhoods were semi-structurally interviewed about the neighborhood HWA facilities and municipal HWA activities. A rapid coding qualitative analysis approach was applied per topic. The topics were citizens' healthy living description, personal circumstances, and satisfaction with foot and cycle paths, sports facilities, playgrounds, green spaces, museums and theaters, community centers, churches, healthcare, school, food supplies, contact with neighborhood, unfamiliar and/or unused activities, familiar and used activities, unavailable but desired (lacking) activities, and reaching citizens. RESULTS: The utilization of HWA facilities and activities was influenced by the overarching themes of social cohesion, familiarity, reaching citizens, maintenance, safety, physical accessibility, financial accessibility, social accessibility, fit with personal context, and fit with the neighborhood's specific needs. Different overarching themes stood out across different facilities and activities. LPTs indicated the overarching themes needed in combination with one another for a specific activity or facility to increase utilization. For example, the LPT regarding foot and cycle paths was "accessible, safe, and maintained foot and cycle paths". The LPTs regarding familiar and used activities were "customized activities; information provision (e.g., about possibilities to join without paying); social contact, meeting others, and everyone feels included". CONCLUSION: Conducting inclusive qualitative research from a systems perspective among citizens living in low SEP neighborhoods has contributed valuable insights into their needs. This enables practical implementation of HWAs by providing a deeper understanding of the LPTs within the HWA system. LPTs can help HWA stakeholders to further develop current HWAs toward systems approaches. Future research could study the leverage points that may contribute to LPT implementation.

Healthy together Victoria and childhood obesity study: effects of a large scale, community-based cluster randomised trial of a systems thinking approach for the prevention of childhood obesity among secondary school students 2014-2016.

BACKGROUND: Healthy Together Victoria (HTV) was a Victorian Government initiative that sought to reduce the prevalence of overweight and obesity through targeting chronic disease risk factors including physical activity, poor diet quality, smoking, and harmful alcohol use. The intervention involved a boosted workforce of > 170 local-level staff in 12 communities; employed to deliver system activation around health and wellbeing for individuals, families and communities. A cluster randomised trial (CRT) of a systems thinking approach to obesity prevention was embedded within HTV. We present the two-year changes in overweight and obesity and associated behaviours among secondary school students across Victoria, Australia. METHODS: Twenty-three geographically bounded areas were randomised to intervention (12 communities) or comparison (11 communities). Randomly selected secondary schools within each community were invited to participate in the trial in 2014 and 2016. Students in Grade 8 (aged approximately 13-15 years) and Grade 10 (aged approximately 15-16 years) at participating schools were recruited using an opt-out approach across July-September 2014 and 2016. Primary outcomes were body mass index (BMI) and waist circumference. Secondary outcomes were physical activity, sedentary behaviour, diet quality, health-related quality of life, and depressive symptoms. Linear mixed models were fit to estimate the intervention effect adjusting for child/school characteristics. RESULTS: There were 4242 intervention children and 2999 control children in the final analysis. For boys, the two-year change showed improvement in intervention versus control for waist circumference (difference in change: - 2.5 cm; 95% confidence interval [CI]: - 4.6, - 0.5) and consumption of sugar-sweetened beverages per day (< 1 serve: 8.5 percentage points; 95% CI: 0.6, 16.5). For girls, there were no statistically significant differences between conditions. CONCLUSIONS: HTV seemed to produce favourable changes in waist circumference and sugar-sweetened beverage consumption for boys, however, no effect on BMI was observed. Although the HTV intervention was cut short, and the period between data collection points was relatively short, the changes observed in HTV contribute to the growing evidence of whole-of-community interventions targeting childhood obesity. TRIAL REGISTRATION: This trial is unregistered. The intervention itself was a policy setting delivered by government and our role was the collection of data to evaluate the effect of this natural experiment. That is, this study was not a trial from the classical point of view and we were not responsible for the intervention.

A Systems Approach to Biomechanics, Mechanobiology, and Biotransport.

The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education. Systems approaches are yielding new insights into human biology by leveraging state-of-the-art tools, which could ultimately lead to more informed design of therapies and medical devices for preventing and treating disease as well as rehabilitating patients using strategies that are uniquely optimized for each patient. Educational approaches can also be designed to foster a foundation of systems-level thinking.

Adoption of C-reactive protein rapid tests for the management of acute childhood infections in hospitals in the Netherlands and England: a comparative health systems analysis.

BACKGROUND: The adoption of C-reactive protein point-of-care tests (CRP POCTs) in hospitals varies across Europe. We aimed to understand the factors that contribute to different levels of adoption of CRP POCTs for the management of acute childhood infections in two countries. METHODS: Comparative qualitative analysis of the implementation of CRP POCTs in the Netherlands and England. The study was informed by the non-adoption, abandonment, spread, scale-up, and sustainability (NASSS) framework. Data were collected through document analysis and qualitative interviews with stakeholders. Documents were identified by a scoping literature review, search of websites, and through the stakeholders. Stakeholders were sampled purposively initially, and then by snowballing. Data were analysed thematically. RESULTS: Forty-one documents resulted from the search and 46 interviews were conducted. Most hospital healthcare workers in the Netherlands were familiar with CRP POCTs as the tests were widely used and trusted in primary care. Moreover, although diagnostics were funded through similar Diagnosis Related Group reimbursement mechanisms in both countries, the actual funding for each hospital was more constrained in England. Compared to primary care, laboratory-based CRP tests were usually available in hospitals and their use was encouraged in both countries because they were cheaper. However, CRP POCTs were perceived as useful in some hospitals of the two countries in which the laboratory could not provide CRP measures 24/7 or within a short timeframe, and/or in emergency departments where expediting patient care was important. CONCLUSIONS: CRP POCTs are more available in hospitals in the Netherlands because of the greater familiarity of Dutch healthcare workers with the tests which are widely used in primary care in their country and because there are more funding constraints in England. However, most hospitals in the Netherlands and England have not adopted CRP POCTs because the alternative CRP measurements from the hospital laboratory are available in a few hours and at a lower cost.

Supporting whanau during COVID-19 pandemic in Aotearoa New Zealand: a systems thinking case study.

BACKGROUND: The Aotearoa New Zealand COVID-19 pandemic response has been hailed as a success story, however, there are concerns about how equitable it has been. This study explored the experience of a collective of Maori health and social service providers in the greater Wellington region of Aotearoa New Zeland delivering COVID-19 responses. METHODS: The study was a collaboration between a large urban Maori health and social service provider, Takiri Mai Te Ata whanau ora collective, and public health researchers in Aotearoa New Zealand. Two online workshops were held with staff of the Maori service provider, collectively developing a qualitative causal loop diagram and generating systemic insights. The causal loop diagram showed interactions of various factors affecting COVID-19 response for supporting whanau (Maori family/households) at a community level. The iceberg model of systems thinking offered insights for action in understanding causal loop diagrams, emphasizing impactful changes at less visible levels. RESULTS: Six interacting subsystems were identified within the causal loop diagram that highlighted the systemic barriers and opportunities for effective COVID-19 response to Maori whanau. The medical model of health service produces difficulties for delivering kaupapa Maori services. Along with pre-existing vulnerability and health system gaps, these difficulties increased the risk of negative impacts on Maori whanau as COVID-19 cases increased. The study highlighted a critical need to create equal power in health perspectives, reducing dominance of the individual-focused medical model for better support of whanau during future pandemics. CONCLUSIONS: The study provided insights on systemic traps, their interactions and delays contributing to a relatively less effective COVID-19 response for Maori whanau and offered insights for improvement. In the light of recent changes in the Aotearoa New Zealand health system, the findings emphasize the urgent need for structural reform to address power imbalances and establish kaupapa Maori approach and equity as a norm in service planning and delivery.

A Systems Map of the Challenges of Climate Communication.

Over the past sixty years, scientists have been warning about climate change and its impacts on human health, but evidence suggests that many may not be heeding these concerns. This raises the question of whether new communication approaches are needed to overcome the unique challenges of communicating what people can do to slow or reverse climate change. To better elucidate the challenges of communicating about the links between human activity, climate change and its effects, and identify potential solutions, we developed a systems map of the factors and processes involved based on systems mapping sessions with climate change and communication experts. The systems map revealed 27 communication challenges such as "Limited information on how individual actions contribute to collective human activity," "Limited information on how present activity leads to long-term effects," and "Difficult to represent and communicate complex relationships." The systems map also revealed several themes among the identified challenges that exist in communicating about climate change, including a lack of available data and integrated databases, climate change disciplines working in silos, a need for a lexicon that is easily understood by the public, and the need for new communication strategies to describe processes that take time to manifest.

The Need to Focus More on Climate Change Communication and Incorporate More Systems Approaches.

Society is at an inflection point-both in terms of climate change and the amount of data and computational resources currently available. Climate change has been a catastrophe in slow motion with relationships between human activity, climate change, and the resulting effects forming a complex system. However, to date, there has been a general lack of urgent responses from leaders and the general public, despite urgent warnings from the scientific community about the consequences of climate change and what can be done to mitigate it. Further, misinformation and disinformation about climate change abound. A major problem is that there has not been enough focus on communication in the climate change field. Since communication itself involves complex systems (e.g. information users, information itself, communications channels), there is a need for more systems approaches to communication about climate change. Utilizing systems approaches to really understand and anticipate how information may be distributed and received before communication has even occurred and adjust accordingly can lead to more proactive precision climate change communication. The time has come to identify and develop more effective, tailored, and precise communication for climate change.

Tailoring functional two-dimensional nanohybrids: A comprehensive approach for enhancing photocatalytic remediation.

Photocatalysis is gaining prominence as a viable alternative to conventional biohazard treatment technologies. Two-dimensional (2D) nanomaterials have become crucial for fabricating novel photocatalysts due to their nanosheet architectures, large surface areas, and remarkable physicochemical properties. Furthermore, a variety of applications are possible with 2D nanomaterials, either in combination with other functional nanoparticles or by utilizing their inherent properties. Henceforth, the review commences its exploration into the synthesis of these materials, delving into their inherent properties and assessing their biocompatibility. Subsequently, an overview of mechanisms involved in the photocatalytic degradation of pollutants and the processes related to antimicrobial action is presented. As an integral part of our review, we conduct a systematic analysis of existing challenges and various types of 2D nanohybrid materials tailored for applications in the photocatalytic degradation of contaminants and the inactivation of pathogens through photocatalysis. This investigation will aid to contribute to the formulation of decision-making criteria and design principles for the next generation of 2D nanohybrid materials. Additionally, it is crucial to emphasize that further research is imperative for advancing our understanding of 2D nanohybrid materials.

Systems thinking for local food environments: a participatory approach identifying leverage points and actions for healthy and sustainable transformations.

BACKGROUND: Current local food environments encourage poor diets, posing a significant threat to public and planetary health. Acknowledging and addressing its inherent complexity is vital to making meaningful improvements to the food environment. Using a participatory approach with local stakeholders, this study aims to gain insight into the factors and mechanisms underlying the local food environment and to identify leverage points and system-based actions to foster healthy and sustainable local food environments. METHODS: A systems-thinking approach was used in a Dutch municipality in 2022. Two group model building (GMB) workshops were held with community stakeholders (e.g. local policymakers, retailers and residents). During the first workshop (June 2022), factors and mechanisms influencing the local food environment were identified and visualized through a causal loop diagram (CLD). During the second workshop, leverage points and system-based actions to improve food environments were identified by the stakeholders. Four months after (October 2022), an action-implementation meeting was organized to stimulate the implementation of selected actions. Progress was monitored through brief telephone interviews 6 and 12 months after the second workshop. RESULTS: The CLD visualises the factors and mechanisms influencing the local food environment from the point of view of the community stakeholders. The CLD consists of 46 factors shaping the local food environment, which were categorized into four identified subsystems: societal factors, individual, socio-economic factors, commercial factors and political factors. Eight leverage points were identified within the CLD, for example, 'lobby from food industry', 'governmental food policies' and 'e-commerce and platform economy'. Stakeholders formulated 20 actions targeting the identified leverage points. During the action-implementation meeting, long-term plans were created for five actions. After 1 year, only one participant (policy advisory role) remained actively engaged in three of these actions. CONCLUSIONS: This study yields insight into the numerous factors and mechanisms underlying the local food environment and identified system-based actions as perceived by local stakeholders to improve this food environment locally. The CLD offers stakeholders valuable insights on employing a systems approach when enhancing food environments. More research is necessary, especially into the long-term processes and effects of implementing system-oriented actions to improve local food environments.