Despite an intensive focus on workers’ health during recent decades, the prevalence of work-related diseases remains unchanged in Denmark and internationally. Therefore, USA and Australian researchers have initiated new paradigms for integration of health promotion, prevention of work-related disease, and organization of work. Inspired by the Australian WorkHealth Improvement Network program (WIN), this paper describes the background, design, intervention methodologies, and evaluation methods of an Integrated Approach to Health, Wellbeing, and Productivity at Work (ITASPA) intervention aiming to prevent work-related injuries and diseases and promote the health, safety, and wellbeing of the worker.Using a stepped wedge design, worksites will be enrolled at baseline and offered the intervention starting at different times. Data will be collected at baseline, before the off-set of the intervention, and after each implementation period. The effect evaluation will be based on a mixed-methods approach. The qualitative data are based on semi-structured interviews and focus groups. The quantitative data consists of questionnaires, anthropometrics, and resting blood pressure and will be analyzed based on the intention-to-treat principle in linear mixed models with random slope and intercept.Integrated interventions are shown to increase overall health and safety at worksites more effectively and rapidly than more narrowly focused programs. Still, previous integrated interventions are lacking successful implementation. In ITASPA, the effects of the intervention is tested in a strong scientific mixed-methods design. Thus, the ITASPA project contributes to the knowledge about what characterizes a best practice for the implementation of integrated worksite interventions.ITASPA is retrospectively registered in Clinicaltrials.gov on May 19, 2023 (NCT05866978). Despite the past decades’ increased focus on workers’ health, the Danish, as well as international prevalence of work-related diseases and injuries, remain stable , 2. In DThe American Total Worker Health (TWH)  and the Compared to the American work health system, the Australian system is more similar to the Danish, and the systematic approach and data collection in the WIN concept are possible to operationalize and have documented beneficial effects . TherefoThe aim of the ITASPA project is to investigate the effect of the WIN program in a Danish context. The hypothesis is that an integrated approach will improve the health of employees in terms of fewer MSDs, improved psychosocial wellbeing and workability, and strengthened occupational safety culture. Furthermore, the ITASPA project aims to examine the degree of implementation of the initiated initiatives and identify barriers and facilitating factors for implementation. This contributes to the knowledge about what characterizes best practices for the implementation of integrated worksite interventions.ITASPA is a worksite intervention, conducted in a stepped wedge design Fig.  16]. Th. Th16]. The study was approved by the Danish data protection agency  and the Ethics Committee for the regional capital in Denmark  and will be conducted in accordance with the Helsinki declaration. The first version of the Clinicaltrials.gov registration for ITASPA is registered on May 19, 2023 (NCT05866978).To increase the transferring of the WIN program to a broad variety of Danish worksites, both public and private worksites are aimed to be enrolled. The worksites will be enrolled on basis of their willingness to perform the ITASPA activities during paid worktime and participation in the scientific evaluation of the ITASPA project. Workers will be included in the scientific evaluation of the ITASPA project by the following criteria: aged 18 – 67 years old at baseline; employed at one of the enrolled worksites ≥ 20 h/week; not being pregnant; ability to understand and speak Danish or English; providing an informed signed consent prior to participation.An information meeting at the worksites will be held before initiating the intervention. At the meeting, the background and aim of the ITASPA project are introduced. All workers will be invited to fill out a screening questionnaire in which they can choose to sign up for participation in the scientific evaluation.The sample size estimations were based on effect expectations in MSDs, on a scale ranging from 0–10, an expected variance of 2.1, an Alpha value of 0.05, and a power of 80%. The estimation showed a cluster size of 65 participants to identify a statistically significant effect, at a 5% level, of the worksite intervention.The ITASPA project will be organized by a steering group consisting of the ITASPA project managers, representatives from the senior management at the enrolled worksites, and the ITASPA facilitators from the Department of Occupational and Social Medicine at Holbæk Hospital, Denmark Fig. . MoreoveThe steering group will collect and choose relevant tools and methodologies to establish a Package of Change. This package encompasses descriptions of the processes in ITASPA, evidenced examples of previous successful worksite interventions similar to ITASPA, and the present work environment policy, program, and practice at the enrolled worksites.At each worksite, an ITASPA committee will be established Fig. . In accoBefore the offset of the intervention, the ITASPA committee will be educated by the ITASPA facilitators in the ITASPA concept and the Package of Change.• Plan: Thorough planning of the initiative, clarification of expectations of outcomes, and agreements on data collection.• Do: Implementation of the planned actions as well as data collection.• Study: Reflection on effect and learning, data analysis, and identification of unintended negative and positive consequences.• Act: Assessment of either continuation of implementation, adjustments, or testing a new initiative.The education session will be carried out as a workshop . The Short Form of the Örebro Musculoskeletal Pain Screening Questionnaire will be used to measure MSDs [The questionnaire-based interview includes questions about the level of physical activity in occupational and leisure time, eczema, and self-reported health. Functionality will be measured by the ICF-based Work Rehabilitation Questionnaire (WORQ) . Resting heart rate and blood pressure will be measured three times on the left arm after 15 min of sitting at rest using an Omron Model M3, automatic upper arm BP monitor .The objective measurements include body weight (kg), height (m), percent body fat, resting heart rate (beats per minute), and blood pressure (mmHg). Bodyweight, percent body fat, and height will be measured while the participant is wearing light clothes and no shoes. The estimated weight of clothes (1.5 kg) will be subtracted from body weight. Percent body fat will be estimated by bioelectric-impedance-analysis. Both body weight and percent body fat will be measured by a Segmental Body Composition Monitor, Innerscan V, BC545N . If participants have a pacemaker or are pregnant, the analysis of percent body fat will not be made. Body height will be measured on a mobile stadiometer Seca 213 . Body mass index (BMI) will be estimated by the equation of BMI = (body weight (kg)/body height (m)At baseline, and after the periods of implementation, we will collect data on sickness absence, staff turnover, and productivity combined with interviews with the chairperson of the ITASPA committee. These data will be collected for a financial evaluation of the overall ITASPA intervention at each worksite.The implementation of the initiatives will be tracked by the research group using quantitative and qualitative methods, allowing for triangulation of data across methodologies .The quantitative process tracking will be based on the data collected by the ITASPA committees during the implementation periods. Data will be used to monitor the fidelity and dose (the amount of intervention delivered) of the planned initiatives, following the principles of process evaluation .The qualitative process tracking will be based on focus group interviews consisting of members of the ITASPA committee at each worksite after the second learning workshop and an individual semi-structured interview with the chairperson of the ITASPA committee midway through each implementation period. Data on implementation experiences will be collected and feedback on the effect of the chosen outcome, for the particular period of implementation, will be given. This has two purposes: 1) to collect data on factors facilitating and hindering the implementation of the initiatives, and 2) to give feedback to the worksites regarding the effect of the chosen outcome, based on the initiative in the ongoing period of implementation. The focus groups are directed by a semi-structured interview guide including questions about the specific interventions and reflections on intervention delivery, such as observations on contextual factors, barriers, and facilitating factors of intervention implementation . Thus, tData from the health checks will be used to evaluate the effect of the initiatives after each implementation period. Preliminary descriptive analysis will be conducted and discussed with the ITASPA committee after each implementation period to ensure that only beneficial and effective initiatives are continued in the next implementation period and to guide the development of future initiatives.2 test for categorical variables and paired and independent sampled t-test for continuous variables. Furthermore, differences in baseline data between those who want to participate and those who do not want to participate will be analyzed. Where appropriate, results are presented as the mean and standard deviation (Mean ± SD) or visualized in graphs and histograms.Descriptive analyses of baseline data and health check data will be conducted after the implementation periods. Frequencies and distribution of participants across variables will be reported (amount and percentages). Differences between baseline data and the follow-ups within and between participating worksites will be reported by the use of chiThe effect evaluation will be based on a mixed-methods approach, where questionnaire data on MSDs, psychosocial wellbeing, safety culture, and workability will be measured based on the questionnaire-based interviews. The quantitative data will be analyzed based on the intention-to-treat principle in linear mixed models with random slope and intercept. The repetitive measurements within and between participants will be accounted for by nesting participants in clusters at the worksite level. The intervention will be included as a categorical variable with two levels, comparing the intervention period with the control period as a fixed effect in the model. Intercorrelation of repeated measurements will be included in the models as a random effect. Participants missing data on exposure or outcome variables will be excluded from analyses. All analyses will be conducted in SAS version 9.4 and/or SPSS version 27.0.Experiences from each interview midway through the periods of implementation will be analyzed in an overall analysis based on the Model of Knowledge to Action Cycle . This anThe implementation of the project within worksites depends on the consent of the top management. At learning workshops, worksites will be encouraged to share experiences with their work environment initiatives. During this process, company-sensitive information may be shared. Thus, in workshops, it will be pointed out that a duty of confidentiality is expected among companies.Personal information will be obtained from the participants about safety at work, workability, MSD, and psychosocial well-being. Data will be stored and processed as prescribed by the Danish Data Protection Agency and will only be available to researchers involved in this study. Data will be anonymized in analyses and feedback to the worksite will be provided anonymously, and in groups of at least 10 participants. The ITASPA facilitators will discuss any unforeseen ethical aspects with the worksites if they experience any. In this context, the steering group and reference group will be involved as potential sparring partners.The aim of the ITASPA project is to investigate the effects and implementation of the Australian WIN program adapted to the Danish context. The background, design, intervention methodologies, and evaluation methods have been described. Effective interventions aiming to reduce work-related MSDs and mental disorders remain to be established, and to this date only a few integrated worksite intervention studies have been conducted in a Danish context –25.We hypothesize that an integrated approach will improve the health and wellbeing of workers and strengthen the occupational safety culture. Other international experiences show that comprehensive, integrated worker health programs linking health protection and health promotion activities increase overall health and safety at worksites more effectively and rapidly than more narrowly focused programs , 14. ForIn ITASPA, activities are integrated and adapted into existing core tasks, health promotion/disease prevention strategies, and organizational structures at the worksite. Hence, initiatives developed in ITASPA can be integrated across organizational structures. Furthermore, ITASPA involves employees and managers in the development and implementation of initiatives. Such a participatory approach in interventions for workplace improvements has previously shown to effectively improve health conditions such as mental health . HoweverEven though RCTs are the golden standard for intervention studies, it is not always practically possible, nor feasible, to have a control group of employees working at worksites that will not be affected by the intervention. However, the stepped wedged design will function as an RCT as it allows for comparison of control and intervention effects within the same environment, without increasing the risk of contamination between the intervention and control group, which reduces the risk of bias. Moreover, a stepped wedge design can prevent ethical objections arising from withholding an intervention anticipated to be beneficial . In addiSome limitations of the intervention design also deserve to be mentioned. As all employees will receive the intervention, it is not possible to blind participants or those involved in delivering the intervention. Hence, information bias may appear, particularly when outcomes are subjective. E.g. it is possible that participants are likely to report more positive health outcomes due to extended awareness of changes in these conditions after having received the intervention, leading to stronger effect-estimates of the intervention .Furthermore, selection bias may challenge the generalizability of the results: it is plausible that healthy workers are more likely to stay at work longer than those who are injured or made sick from work  (healthyThe companies are randomly sampled, allowing for enrollment of diverse industries. Thus, we are able to investigate if the integrated approach can be translated and be successful in different lines of industries. Previous findings from worksite intervention studies show that the beneficial effects of an integrated worksite intervention are seen across different industries such as cleaning services , healthc


The circular economy (CE) has shown promise for achieving several of the UN’s Sustainable Development Goals, replacing the linear system and reducing negative impacts on the environment. This research aims to assess the effective adoption of CE principles in three cheeses with geographical indication (GI) through an analysis of the practices identified in their respective value chains. Qualitative interviews show the persistence of historical practices that preserve the heritage behind the product, maintain autonomy in relation to external inputs and save energy or make intelligent use of by-products. Radical adoption of CE principles requires innovation to reduce the use of new inputs and greenhouse gas emissions. GI food products are generally not constrained by standards beyond those set by law, but their specifications can be modified, while respecting practices consistent with the link to the terroir. However, the remoteness of small businesses in deep rural areas, far from research centers, is slowing down the transfer of knowledge and the adoption of the latest technologies, particularly in mountainous areas. More participatory research and innovative initiatives are needed to ensure the transition to a circular economy for traditional mountain products, which are strongly linked to local culinary traditions and cultural identity.  In recent years, several studies have been conducted to shape how CE can be adopted as a territorial approach to sustainability. The circular economy (CE) was introduced in 1970 as a model for sustainably transforming the linear economy. The linear system of production used in business models places high pressure on the environment in terms of continuously extracting new resources for production and exacerbating externalities like biodiversity and ecosystems losses, greenhouse gas emissions, pollution, and climate change in the process . With thIn its report of the meeting on sustainable development, the United Nations  stated tCircularity is conceptualized by the expression “resource-product-resource” , which hCE also promotes the moderate use of resources, thus reducing the waste and all environmental impacts of processes and increasing the use of renewable resources. It focuses on extending the life of products with material recycling, technological renovations and a return to the factory. Moreover, CE aims to increase the efficiency of the economic systems as a whole and to minimize negative externalities related to the release of toxic substances, soil, and pollution .In 2020, the European Commission adopted a new Circular Economy Action Plan (CEAP), one of the major elements of the Green Deal agenda. It aims to contribute to sustainability and introduce the concept of circularity in the regions by promoting well-being, socio-economic growth, and the reduction of environmental pressure .The most common definitions and action plans of circularity are the ones from ADEME  and Ellen MacArthur . However, in practice, the geographical and contextual dimension of the circular economy principles is still not clear enough .CE is based on looping ecological practices and the circularity of materials that can be found in one’s own production line or from other companies. It promotes complementarities between different companies at local level, such as the exchange of machinery and materials between the actors of the same territory, an increase in job offers for the local community and the improvement of the quality of employees’ life by adopting circular practices . This could provide more opportunities for the workers to find better jobs connected with the value chains (VC) . CE promMoreover, CE is a multi-level concept, where resource circularity is distributed at two complementary separate economic structures. “High-level” circularity includes R strategies adopted by cluster industries, whereas “lower levels” are targeted towards actors that engage towards circularity, but on a smaller scale. The combination of CE activities at lower levels provides a higher level of circularity .Local production systems present regularities from one place to another. Among the characteristics of these systems, there is always geographical proximity between production units and a strong dependency on local resources, high-level sharing of know-how and active exchanges between the different actors. That is why the direct local business-ecosystem likely directly impacts the potential for CE practices. In the food sector, local production systems are in rural areas but the vast majority are built around and strongly connected with cities where their consumers are located. The more remote areas and/or larger-scale production systems that focus on one product are more oriented towards conventional markets and exports. It is thus adequate/logical to consider that such production systems might implement CE at lower levels.One type of such food system where CE is adopted at lower levels can consist of geographical indications (GI). GIs are intellectual property rights and quality schemes that are used to distinguish products, mainly from the food sector, characterized by a specific quality and reputation linked to their geographical origin . These pMoreover, research shows that the economic dimension is considered more frequently when discussing the sustainability of GI . This isOne rare study  showed tVery little literature that discusses the circular economy in mountain food products or cheese products has been created. Other research is focused on related subjects such as technology of cheese production and by-products transformation, consumers’ perception of mountain cheese products and sustainable agri-tourism/pastoral tourism in mountain livestock farming, etc.The environmental benefits and impacts of GIs systems are thus still not fully understood. On the one hand, they may prove to have conserved CE practices in the sense that they rely on local resources and local connections, but on the other hand, they might be too remotely located to benefit from efficient technologies and exchanges with many production lines in the area. Therefore, the legal definition of GIs traditionally does not address the sustainability dimension, as GIs users primarily focus on intellectual property rights, mostly to enforce the protection of the original name against misuses. The global context is pressing all GIs to examine how to preserve more natural resources and adapt to climate change.Analyzing GIs in connection with CE also sheds further light on the geographical and contextual differences with regard to how CE can or cannot be implemented. This is why we aim to assess the environmental sustainability of geographical indications through the identification of CE principles found in three European PDO cheese products localized in mountain regions. This paper will help identify transitional innovative and collaborative pathways towards the CE and to set up good practices, defined from the VCs, to guide the producers to implement such transitions.The three main research questions raised are: (1) Do GIs adopt circular and sustainable practices? (2) Are these practices historical or innovative? (3) Can the Code of Practice (CoP) highlight sustainable and circular aspects, or should it remain flexible?The findings of these questions will provide a primary understanding of how GIs appropriate CE principles in their VC and the regulatory framework that can promote and support sustainable practices. This research will have a practical implication for producers, by building a cheese VC flowchart that highlights CE and sustainability elements found in the three studied cheese mountain products.This qualitative study analyzes the implementation of CE for three PDO cheese VCs localized in European mountains regions, selected from the project MOVING: Tête de Moine in Switzerland, Alto Molise in Italy and Serra de Estrela in Portugal . As partIn the EU regulation, mountain areas are defined in the legal definition No. 75/268 1975) of Less Favored Areas (LFAs) . A VC en75 of LesThis analysis is based on evidence screening of CE principles among pre-existing qualitative data about the geographical and natural resources, the sustainability, and the resilience in their respective cheese VC. These data were collected by the VC experts of the project MOVING in 2022 and were used in the current research to contextualize each of the VCs. Two co-authors had a practical implication in the data collection phase in Switzerland. They were active in reviewing the synthesis reports based on the data collection for all MOVING case studies. They were also in close contact with the researchers of the other case studies, organizing 10 workshops with the partners of all MOVING case studies and several bilateral in-depth reviews of the cases.We have selected three case studies which are part of the MOVING EU project. These cases are traditional cheeses, being European Protected Designation of Origin (PDO). These cases have been selected because cheeses are traditional in Europe, and because they are located in three different geographical mountain areas of Western Europe: in the Italian Apennines , in the Swiss Jura (Tête de Moine), both of which are located in “wet mountains”, and one in the Serra da Estrela for a PDO cheese of the same name in Portugal in Southern Europe (which are located in “dry mountains”). The mountains are typically far away from the research centers and consumers and suffer from harsh climate and steep terrain. For that reason, applying the CE principle can be even more challenging than for other value chains, and this makes it particularly interesting to explore the situation in cases exposed to severe conditions.In the case of the “caciocavallo cheese”, the producers use different geographic denominations. In the Alto Molise region, where the MOVING project was implemented, different denominations are used, one being “caciocavallo Silano PDO” and another being “caciocavallo di Agnone” officially recognized  as “Prodotto Tradizionale Territoriale”.Tête de Moine is a Swiss mountain type PDO raw cow-milk cheese produced in the Swiss Jura region, in particular in the Alps during summer season, and is managed by the interbranch organization known as “Interprofession”, as defined by Swiss law. It is a strong and democratic association composed of farmers, cheese makers and ripeners responsible for managing the quality, production, protecting the denomination from copy and imitations, as well as marketing of the product. This is all defined in the Ordinance (nr. 919.117.72) on the extension of mutual assistance measures of interbranch organizations and producer organizations.Serra da Estrela is an artisanal PDO cheese made from sheep milk. It is produced from two local sheep breeds from the Cordilheira Central of Portugal. It is produced by several family businesses, in which men are responsible for the shepherding and women for cheese making .Three experts on Tête de Moine, four experts on caciocavallo Silano and caciocavallo di Agnone and one expert on Serra da Estrela were invited to an interview during March and April 2023. Each expert collected available data about CE in his VC and answered the questionnaire administered via video conferencing. The three cheese VCs are different in terms of the institutional framework, the social and economic aspects as well as the natural and geographical context of each of the represented countries.The interviewers introduced the transition from linear economy to CE and explained the waste hierarchy to guide the interview. The 8 experts presented their VC and explained all sustainable or circular practices that were employed in the past and innovative practices adopted recently according to the 5Rs . The queDoes the production part of your value chain include practices related to the “Refuse” of materials?Which of the mentioned practices in the previous question are traditional/historical?Which of the mentioned practices in the previous question are innovative?Are the practices mentioned above specified in the CoP?The 5Rs section is divided into 5 subsections related to one of the R practices. Each R is explained with a definition and a representative example. Four questions are repeated for each subsection, such as:In total, 8 experts participated in the interviews. Interviews were recorded, after asking for formal consent and taking the experts’ approval. Audiotapes were transcribed, serving as the primary data source. Videotapes were used to show the documents shared and determine nuances in the informants’ speech. In addition, interviewers took notes during the discussion to highlight the main elements relative to the study goals, especially circular aspects. The information was then structured in an interview report.The qualitative data collected were analyzed according to two main criteria. Firstly, the practices identified were classified per VC based on the 5Rs categories. Secondly, each practice was also assigned to one of the following five categories: historical and still existing, historical abandoned, historical upgraded, innovative, and present in the CoP. This classification helped us to develop a visual representation of the CE practices identified within the VC. A flow chart of the cheese processing was developed to emphasize the CE practices identified. Moreover, an applicability analysis of possible circular practices to be applied in the cheese production sector was created as a guide of good practices for producers.From the interviews, it appears that CE is not very well known nor mastered by the experts. Based on the results, experts are averagely knowledgeable about CE (3.67 ± 0.52) and moderately confident in implementing its principles in their VC (3.67 ± 0.58). One VC out of the three participated in CE projects. Nevertheless, 22 practices contributing to the CE in cheese VCs have been identified and are presented and further analyzed in this chapter of the paper. A summarizing table of the practices can be found in the Several innovative or historical practices, specified in the code of practice or not, in line with the waste hierarchy are presented in The results show that “Reduce” and “Repurpose’’ were the most widespread practices among these VCs : a totalWith the industrialization and the legislative framework of the CoP, some of these actions have been abandoned or upgraded to better and more innovative alternatives. “Reduce” is associated with the use of green technologies to reduce emissions and the use of non-renewable energy.“Reuse” and “Refuse” were moderately adopted: five practices were identified for each R), whereas “Recycle” was the least common, with only two occurrences. Practices related to the “Refuse” of certain materials exist in the VCs. Some of these practices are mentioned in the CoP. This is because the CoP strictly mentions the use of local pastures and breed, the materials and the machinery authorized. In the case of Serra da Estrela, a single press machine may be used by the producers.However, results show that practices can be categorized in 6Rs categories instead of 5 . 3 “ResaHistorical sustainable elements exist in all three products, including practices that contribute to the qualitative and traditional aspect of the VC, which are the focus of GIs.Each of the practices identified can be classified into five main categories: “Historical, still existing”, “Historical abandoned”, “Historical upgraded”, “Innovative” circular practices and practices specified in the CoP or not .Historical practices were widely identified in all products. Only a few practices were “upgraded” or “abandoned”. While looking at the presence of these practices in the CoP, only historical and still existing practices are mentioned.In the table in the Tête de Moine production includes more practices in terms of sustainability, such as the obligation for livestock to graze, the use of agricultural fodder and the maintenance of family farming on a human scale. The distance between the cheese factory and the farm is not allowed to exceed 20 km, and there are daily quality controls for raw milk. Milk is transported in less than 24 h and transformed into cheese, as a way of guaranteeing the high quality of the final product. On the other hand, Serra da Estrela cheese is an artisanal cheese that relies mainly on human activity and is produced from two local breeds. A certification system at the production level for each cheese by a casein mark and a registration of breed in gynecological books is implemented as a traceability system and quality guarantee. For Alto Molise, the main sustainable practice is dual-purpose breeding, and the main qualitative aspects are the animal farming practices and the production of local fodder.In four cases, these practices are mentioned in the code of practices and are guaranteed by a strong legislative system. These elements highly depend on the history, the tradition, and the CoP of the product, as well as the juridical/governmental system of the country and the management system adopted by the producer himself.Certain historical practices were gradually abandoned over time due to technological advancements. In the past, shepherds in Portugal made daily trips to the mountains. In summer, between July and August, sheep would go to the mountain areas to pasture and back to the pen where they slept and were milked. Currently, this practice is almost entirely abandoned by shepherds. Nowadays, farmers keep their sheepfold in mountain areas, and they are more concentrated in the foothills. Cattle used to produce Alto Molise cheese were left to graze in summer in the mountains of the Apennines. Over time, this 2Rs practice “Refuse, reduce” was also replaced with semi-intensive farming, leading to a decline in direct mountain pasturing and increase in stall feeding.Certain producers have regained interest in some of these practices and, recently, started to reintroduce them to their VC. Dual-purpose breeding in Alto Molise VC was a very common sustainable practice in the past. Mixed milk and meat farming has three circular purposes: Refuse, Reduce and Repurpose, because having animals that produce both meat and milk means keeping less animals, reducing the need for feed and repurposing what was once only a waste or side-product . This practice was widespread and had a positive impact on biodiversity and maintaining habitats. The reduction in grazing along with the population and farms has led to a decrease in grassland and the development of forests. After a serious decline and abandonment of this practice, farmers are regaining interest in this type of breeding system.In certain cases, by-products leave the VC for other transformations or can be transformed on site. One example is the use of dried whey in the pharmaceutical industry. In this regard, some cheese VCs are left with huge amounts of whey because they are unable to afford the extra costs of transporting or transforming it. As seen in Alto Molise VC, producers tend to pay firms from the same area to pick up the whey. Tête de Moine producers concentrate the whey to reduce the volume and transport larger amounts for other industries, whereas for Serra da Estrela producers, transforming the whey on site into a ricotta-like cheese called “Requeijão” is an important part of their revenue. This “secondary” cheese is also a PDO product.On the other hand, many VCs are adopting technologies to reduce the consumption of non-renewable energy by installing solar panels and wind turbines or even digesting some by-products into biogas. It is essential to highlight that none of these innovative practices are covered by the CoP.Recently, certain producers of Tête de Moine have been investing in a digestive plant that turns whey into biogas to valorize the huge quantities produced and reduce the consumption of non-renewable resources. This was achieved by the collective system put in place in the Swiss Jura, the “Interprofession” mentioned above, to support the producers in achieving economic diversification and sustainable growth.For these VCs, the CoP specifies generally historical practices such as the origin of the inputs, the local breed and the machinery and materials used. They are strictly specified to preserve the tradition behind the product and to protect the factors that play a huge role in the characteristics of the product. For example, raw milk in Tête de Moine affects the taste and quality of the final products.To better organize and structure the process, it is possible to create connections and collaborations between different stages of the VC. This represents the flux of materials and energy in a circular manner. As seen on the right, at the farm level, in the case of Serra da Estrela, the shepherds sell the wool to produce “burel” fabric. The lamb is as well sold and marketed as a PDO product from the region. In the Italian case, calves, baled hay and sometimes whey are sold for dual-purpose farms. This shows the connection of the cheese production with other types of VCs.Certain PDO specifications limit the farmers to the use of the local pastures only, as seen in “Refuse” practices. Other quality products are allowed to be produced only with raw milk (“Refuse” of heat-treated milk), to market a cheese product with distinct organoleptic characteristics.At the transportation level, producers tend to use reusable materials to move the milk from the farm to the cheese dairies, such as inox tanks or high-density plastic containers. Regardless of the transportation method, cheese VC can be geographically limited with certain PDO specifications linked to the local resources and the distance between the farm and cheese maker. For Tête de Moine, the distance rarely exceeds the kilometers specified due to the limited operational territory in the CoP and past historical proximity between the cheese factory and the farms. As explained by  the orgaAt the heart of the flow chart, numerous fluxes connected to the same production plant or outside the VC of materials and inputs are drawn  is reused multiple times before another one is prepared.Since water is an essential component of cheese production, water collection or neutralization systems are put in place to reduce the usage of water and reuse it in the industry.At the maturation stage, natural cellars can be specified in the CoP of PDO products. These cellars can maintain the necessary temperatures and humidity with no need for electric supply.At the last two steps of the cheese VC flow chart, packaging was less frequently sought during the research. This is because certain VC are still testing new packaging to conserve quality and reduce plastic consumption. On site, Serra da Estrela cheese is sold with paper packaging. Recyclable or returnable packages can be an investment that will allow cheese producers to reduce single-use plastic and increase reuse and recycling.Finally, before the cheese is distributed for consumption and sale, different quality controls are performed. As seen at the left of the chart, if the quality control of Tête de Moine shows that the cheese is not suitable for human consumption, it is often “Repurposed” as animal feed or used to produce fondue cheese, grated cheese or destroyed in the case of bad-quality cheese, whereas if Serra da Estrela cheese is not sold, it is re-integrated in the VC, matured for longer and marketed as an aged PDO version of the cheese known as Queijo Serra da Estrela Velho.Based on the results from the interviews, an analysis of circular practices in the cheese VC was elaborated . It provThese targets, as the most frequently emerging action plans identified during the interviews, are defined based on the environmental sub-themes found in SAFA guidelines by the FAO: Sustainability Assessment of Food and Agriculture systems (2014) .The cost, expressed by an ascending 5 scale “+” sign, was estimated based on the discussions from the three interviews with the experts about the cost-efficiency of the practices or technologies. The benefits were also estimated and summarized based on the information collected during the interviews that took place with the experts of the VC.The results from the interviews conducted shed light on different factors that seemed fundamental for the adoption of CE. The natural capital encompasses the environmental characteristics, the local resources and ecosystems present in each of the regions. This includes elements such as the water, soil, biodiversity, the weather  and local breeds and animals.The human capital represents the local knowledge and know-how, expressed through the technical and technological skills in utilizing the natural resources and benefiting from the geographical characteristics. These skills are demonstrated by the farm management techniques and heritage preservation, as evidenced by the Alto Molise region with its dual-purpose breeding. Local actors contribute significantly to cultural identity by preserving traditional and historical gastronomy rooted in the community, particularly within the CoP associated with certain GI products. For instance, Serra da Estrela cheese production is artisanal, with only one machine permitted within the CoP.However, stakeholders lack access to research institutions. To address this gap, action should be taken to ensure knowledge is transferred, including insights into market trends. Research centers provide up-to-date studies and technologies, offering participatory education and peer learning that can empower the local human capital with innovative techniques aligned with CE objectives. Knowledge transfer covers not only the theoretical principles but also technical and practical support. This bidirectional exchange, facilitated through communication platforms, will remove the gap between the remoteness of mountain producers and research establishments, with a specific focus on CE principles.Public actors and local authorities provide the constitutional and structural framework for transitioning towards a CE. Previous work on agriculture research impact  shows thThrough organized communication between the three actors of the territory, emphasis is placed on the social and natural capitals of the region. Stakeholders, research institutions and local authorities can collaboratively adopt CE principles, facilitating a smooth transition from the linear economy. These intra-dimensions should consolidate their efforts, corresponding to the cycle shown in An economic system contributes to environmental sustainability when its activities help to preserve ecosystems and natural resources. This implies a transition towards renewable resources, waste-management plans and sustainable technologies. CE promotes ecological activities linked to minimizing waste, extending the life of resources and increasing efficiency. It is a “multi-level system”  that funLocal production systems such as GIs are characterized by the geographical proximity between production units, local resources, and the knowledge transfer over the years. With the current rise of climate change, the loss of biodiversity and socio-economic problems, the CE approach has been raised as a solution to the challenges of the territory in terms of resilience, valorization and mobilization of regional government and collective actors .(1)Do GIs adopt circular and sustainable practices?This research addresses the concept of CE within PDO cheese products localized in mountain areas. Three research questions have been raised and discussed throughout this study.Mountain agriculture provides ecosystem services that help conserve biodiversity and natural resources. It supports the economic development of mountain regions using local and quality materials. From a societal perspective, agriculture in these areas helps conserve the traditional and historical gastronomy of the community. For these reasons, many European or international mountain products are registered as geographical indications to protect the heritage and maintain their production .(2)Are these practices historical or innovative?However, the LFA areas are characterized by low input, high cost and decreased yield due to the socio-economic constraints and environmental challenges . DespiteOn one hand, based on the results, local producers successfully maintained historical practices that have existed for several decades in order to remain autonomous and independent and preserve the legacy behind the product. The concept of circularity in these rural regions is integrated in their practices via the sustainable use of natural resources such as the Reuse and Repurpose of by-products and Reduction in waste. These practices have been shared throughout the generations. In areas with geographical handicaps, machinery and innovation can be challenging to introduce due to a lack of technical knowledge, funds, and geographical conditions. As such, the production system is highly dependent on physical power.Compared to their national reference, the farms that produce these three PDO cheeses are remarkably smaller  and locaOn the other hand, technologies—particularly green innovation—can be adopted to increase efficiency and decrease the negative effects on the environment. Valorizing by-products into new transformations plays an important role in the profitability for the producers, financially and to achieve self-sufficiency. This is the case where by-products had higher potential and benefit in including innovation rather than supporting the historical action.Similarly, cheese GI producers are experimenting with different green technologies to help them adapt their production to the current environmental challenges and market needs, especially climate change, without threatening the reputation of their product. Tête de Moine producers are trying to implement a “cold maturation” phase, which prevents a production surplus, in certain periods around the year.(3)Can the Code of Practice (CoP) highlight sustainable and circular aspects, or should it remain flexible?This confirms that CE does not necessarily imply modernization, technologies, and machinery. Historical knowledge holds value in reproposing previous habits that benefit the natural environment and the profitability of the VC. CE can and should also consider the living beings involved in these production systems, like cows, sheep and pigs on farms. Nevertheless, the CoP rarely highlights sustainability or circularity in the specifications. Very few of the identified practices were significantly present in the CoP. This is due to the fact that this label was created as an economic tool  to creatTherefore, with the emerging needs and challenges, the CoP of GIs can evolve in terms of the tradition, history, and the characteristics of the product. Ref.  discusseDebate around amendments of the CoP to balance between innovation and tradition are rising . Ref. 3 indicateSince GI are not “static museums” , transitResults show that the interviewees are not entirely confident in their CE knowledge. The exposure to CE concepts and transition depends on whether the experts were invested in CE projects within their VC or participated in research in the territory. To this end, a continuous learning process through knowledge exchange between actors of the same territory can help GI producers find long-term solutions. More importantly, a specific focus should be placed on re-educating the producers about the benefits of their previous circular habits and to support them in maintaining these historical actions, including those which may have been abandoned by the VC. This can be achieved through collective organisms, national institutions or regional authorities which can offer a space for exchanging knowledge and expertise with the stakeholders involved. External perspectives from researchers, policymakers, public authorities and consumers are crucial to identify the societal demands and the transitions needed, to raise awareness and to find sustainable solutions for the production system in place. In France, producers form an association known as “defense and management organization”  that represents their interests as one and is supported by the national institute of origin and quality (INAO). INAO is directly linked to the French Ministry of agriculture. Such bodies can offer opportunities for communication between the different internal and external actors of the territory in question.Moreover, a range of responsibilities are reliant on market dynamics and consumer behavior. Producers should embrace the adopted practices that contribute to the CE while marketing the product on the international market, especially to local consumers. These practices encompass not only innovative techniques, but also historical and traditional methods. Such a marketing strategy, in response to the rising socio-economic and environmental demands, will help valorize the production system used in the VC and recognize the associated heritage and patrimony, particularly within the local context.Strengthening the set of actors participating in the decision-making process of the territory plays an important role in the institutional transformation. It helps define strategies, guidelines and regional policies that improve their living conditions as a community. Synergies between the public and private stakeholders organize responsibilities and functions among the actors and guarantees control of the VCs in question. They should also provide the technical and financial support for stakeholders to perform experimental projects for modern circular practices. This will help contribute to territorial development through achieving resilience and sustainability of the VC and the area . In thisThe evidence screening of circular economy principles is captured in the three cheese case studies, but these findings are not conclusive for all GIs. The success of maintaining historical practices and implementing innovative practices of circularity is measured by identifying the 6Rs instead of 5Rs. This is because certain by-products leave the VC and are sold to another for ulterior transformation. Articles discussing the environmental sustainability of quality products through the identification of CE aspects are scarce. Additional research and a larger scope are required to identify the circularity aspects within GIs and local food VC.By developing a cheese VC flow chart that stresses the CE practices and the sustainability components of the cheese mountain products, the current research provides theoretical and practical implications. Collaboration amongst VC actors is desirable to ensure the adoption of CE principles at all levels. Assuring the necessary foundation for a seamless cycle of multidimensional elements to adopt CE principles in less-favorable areas of cheese GI VCs is a crucial responsibility for policymakers. Future work could consider other categories of GI mountain products. Future research could consider other categories of GI mountain products. In the context of the MOVING project, our results will be discussed in foresight participatory workshops to take specific needs of the cheese VCs into consideration while reflecting on the policies that will ensure a better future for the mountain communities and ecosystem. The participation of local communities to tackle the challenges and opportunities that are based on the CE principles is key to addressing the Grands Challenges of the Climate Change.Balancing the historical application with technological innovations can take place in local VCs without affecting the specifications and the identity of the product, especially in the case of the CoP of GIs. Validating the circularity of historical abandoned practices by re-educating the producers is necessary to erase the misinterpretation that CE implies. Circular and sustainable practices can include practices that do not include big investments and technological innovations. This can help the producers to achieve a sustainable and resilient production system, with the rise of environmental challenges and the aggravating socio-economic obstacles.Considering that these products are localized in less favored mountain areas, a series of factors may alter the integration of new models of circular economy in their VCs. Production at small-scale sites in mountain regions is highly dependent on the physical activity and know-how of the community. This is also conveyed by a legislative framework of PDO products, with a specific code of practice to be met. Mountain producers may have limited access to the knowledge transfer between stakeholders and research institutes. Moreover, certain technological innovations are not adapted to operate in high-altitude regions with difficult infrastructure conditions. Financial and technical support for small local producers to put in place green technologies are still scarce.This requires institutional support and participatory research at the local and territorial levels, especially in mountain regions, to accompany stakeholders in adopting circular economy practices that contribute to the preservation of the environment, the profitability of their VC and the conservation of the culinary identity of the territory. This calls for access to advisory and training to communicate up-to-date research, trends and innovation that may help local and GI producers mitigate the rising obstacles and implement adapted technologies to their needs and production. Cooperation and effective communication between the producers and different actors contribute to the strength of the territory and the elaboration of long-term solutions.


Pneumococcal pneumonia remains a significant global public health issue. Malaysia has recently added the 10 valent pneumococcal conjugate vaccine to its national immunisation programme. Data on pneumococcal serotype epidemiology is vital for informing national vaccination policy. However, there remains a lack of representative population-based pneumococcal surveillance in Malaysia to help both the assessment of vaccine effectiveness in the country and to shape future vaccine policy. This review explores the history of pneumococcal vaccination, the burden of pneumococcal disease in Malaysia, and offers an insight into the prospects for reducing pneumococcal disease in Malaysia. Streptococcus pneumoniae, has the potential to cause various diseases ranging from the more serious infections including septicaemia, meningitis and severe pneumonia, to milder diseases such as acute otitis media thereby posing a significant public health burden. For example, approximately 80–90% of children up to the age of 5 years suffer from acute otitis media which becomes the leading cause of paediatric healthcare visits and a frequent cause of antibiotic prescriptions, with pneumococci isolated from between 20 and 50% of presentations [Pneumonia remains one of the biggest killers globally and is a leading cause of infant mortality, particularly in South Asia and Western Pacific regions . One of ntations . ImportaS. pneumoniae [There are more than 100 different serotypes of eumoniae  which areumoniae –9.There are several licensed vaccines for use against pneumococcal disease, which stimulate an epitope-specific immune response to the pneumococcal polysaccharide contained in the vaccine. This results in the recognition and immune protection against vaccine serotypes. The first pneumococcal vaccines became available around a hundred years ago, whereby miners were inoculated with various doses of killed pneumococci after a study of pneumococcal pneumonia in that population . There aThe development of PCV’s has been hailed as a major benefit to global health, with an estimated 7 million deaths prevented by 2030 . DespiteMalaysia has a population of over 32 million and is one of the wealthiest and most developed countries in the WHO Western Pacific Region. It is classified by the World Bank as an upper middle-income country and is expected to achieve high income status between 2024 and 2028. However, there are some reforms needed to facilitate this, including improvement to basic health and nutrition. Malnutrition has been associated, for example, with an increased risk of severe childhood diseases such as pneumonia . AccordiIt remains unclear why, relative to other causes of death, Malaysia has a high burden and mortality of pneumonia although it has been shown that early cessation of breastfeeding, exposure to passive smoking and availability of pharmaceutical interventions contribute to worse outcomes in children with pneumonia in Malaysia .The oversight of health systems, policy and infrastructure is the responsibility of the Ministry of Health as a federal government body. In collaboration with the Malaysian Paediatric Association and the Malaysian Society of Infectious Diseases and Chemotherapy, the National Immunisation Programme is strongly supported by the Immunise4Life initiative, an expert-driven community that promotes immunisation of people of all ages.Developed in the 1950s, Malaysia’s national immunisation programme (NIP) was based on the expanded programme on immunisation from the WHO and now includes vaccines against thirteen preventable diseases . DespitePrior to the inclusion of PCV10 in the NIP, PCV’s were available in Malaysia from around 2005, with private health care facilities offering PCV7, and then PCV10 or PCV13, to those who could afford and access the vaccine . During The Pakatan Harapan Government will also provide compulsory pneumococcal vaccination for all children under the age of 2 years, as is the practice in many other countries” [The commitment to nationwide pneumococcal vaccination for children was initially included as a political pledge by the Alliance of Hope (Pakatan Harapan) in their manifesto during the 14th General Election in 2018 as a statement of “untries” . This countries” . Howeveruntries” . A cost-untries”  provideduntries” .Following the introduction of PCV, the reported uptake of the vaccine between January and September 2021 was 95% for the first dose, and just slightly lower at 93% for the second which is much higher than the original 71% target . MalaysiUnlike privately available vaccines, those included in the NIP are free for children, except foreigners. The Malaysian government is committed to ensuring high coverage is reached, and that there is a strong surveillance and monitoring system to assess disease epidemiology . This inIn 2011, a consensus was reached among paediatricians from both public and private sectors to include PCV in the National Childhood Immunization program due to its high efficacy. However, the Committee for Vaccine Use and Cost has proposed a further examination of the cost-effectiveness of introducing PCV into the National Immunization Program.Hence, in 2014, to assess the efficacy, safety, effectiveness, cost-effectiveness, and organizational aspects of PCV10 and PCV13, a Health Technology Assessment (HTA) was conducted prior to its inclusion in the National Childhood Immunization program. The HTA report on child immunisation commented on the 23 valent polysaccharide vaccines being poor at generating immune responses in children for the protection against pneumococcal disease . The ComIn accordance with the NIP, childhood immunisation with PCV10 follows a three-dose schedule, at four months, six months and fifteen months of age for those children born on or after the 1st January 2020, with an adjusted schedule for children already above the age of five months. Despite the risk of infection in the elderly population, pneumococcal polysaccharide vaccination has not been added to the NIP but is recommended by the Malaysian Society of Infectious Diseases and Chemotherapy . It is rNotably, it has also been stated that priority should be given to infant coverage of conjugate vaccination which in turn will provide herd immunity effects to the older populations . It was S. pneumoniae in young children, which is a prerequisite for the development of disease, the surveillance of serotype epidemiology is deemed essential. Like many other countries, the list of notifiable diseases under the Prevention and Control of Infectious Diseases Act 1988 (Act 342) in Malaysia does not explicitly include pneumococcal disease. Surveillance of S. pneumoniae in Malaysia is undertaken through a combination of approaches through the Ministry of Health, such as studies conducted through the Institute for Medical Research and the National Public Health Laboratory. Following the introduction of pneumococcal vaccination, pneumococcal pneumonia should be included in Schedule 1 of the Prevention and Control of Infectious Diseases Act (Act 342), which lists other infectious diseases which are endemic. It is through this act where main surveillance mechanisms are employed.Due to the high prevalence of asymptomatic colonisation of S. pneumoniae has been observed following vaccine rollout and it has been linked to the alteration of genetic arrangement within lineages expressing various capsular types which plays an important role in serotype replacement [As mentioned previously, there are few disease and carriage studies conducted in other areas outside of the capital Kuala Lumpur, and many available studies were from hospitals or medical centres, which carry limitations such as risk of data duplication and difficulty in defining populations . There alacement , 47. Notlacement , thus hiAntimicrobial resistance is an increasing problem globally and the Malaysian government has formed an action plan to reduce the threat of antimicrobial resistance called MyAP-AMR. This focuses on four themes, including public education, surveillance and research, infection control and appropriate antimicrobial use . In MalaNow that PCV15 and PCV20 have been licensed for use , 56, thoWe suggest that further carriage and disease studies are required to assess the effectiveness of the newly implemented PCV10 and to monitor serotype changes in the population. Until there is data available post-vaccine implementation, it will not be possible to assess the morbidity and mortality associated with pneumococcal infection nationally .To the best of our knowledge, no publication has yet determined the relative cost-effectiveness of PCV15 nor PCV20 in Malaysia. Conjugate formulation vaccines have been effective against pneumococcal infections but are not without limitations with a high cost of production, the potential for serotype replacement, and lower efficacy against non-invasive disease. This has led to research into protein-based vaccines, based on the idea that they are not serotype specific and thereby should have greater serotype coverage , 59. As Increases in serotypes not covered by the 10-valent conjugate may result in the need to switch to higher-valency vaccines. Our recent review showed that before the introduction of PCV, the majority of serotypes most prevalent in Malaysia were included in PCV10, with serotype 19 F being the most common serotype across pooled data from invasive, non-invasive and carriage studies  and was S. pneumoniae remains a leading cause of global morbidity and mortality in children and adults. Malaysia has made an important step towards reducing the burden of disease by adding PCV10 to its NIP. However, there is a need for improved surveillance to understand the impact of the vaccine on circulating pneumococci in both disease and carriage. Nationwide or sentinel carriage studies across Malaysia should be considered, ensuring representation of the whole population, which will assist with understanding the impact of PCV. With the field of pneumococcal vaccine research constantly evolving, Malaysia should also continually assess the potential for implementation of higher valency vaccines to help reduce the burden of pneumonia.


To develop public health intervention models using micro-simulations, extensive personal information about inhabitants is needed, such as socio-demographic, economic and health figures. Confidentiality is an essential characteristic of such data, while the data should reflect realistic scenarios. Collection of such data is possible only in secured environments and not directly available for open-source micro-simulation models. The aim of this paper is to illustrate a method of construction of synthetic data by predicting individual features through models based on confidential data on health and socio-economic determinants of the entire Dutch population.n = 16,778,708), all socio-demographic information except lifestyle factors was available. Lifestyle factors were available from the 2012 Dutch Health Monitor . Regression model was used to sequentially predict individual features.Administrative records and health registry data were linked to socio-economic characteristics and self-reported lifestyle factors. For the entire Dutch population (The synthetic population resembles the original confidential population. Features predicted in the first stages of the sequential procedure are virtually similar to those in the original population, while those predicted in later stages of the sequential procedure carry the accumulation of limitations furthered by data quality and previously modelled features.By combining socio-demographic, economic, health and lifestyle related data at individual level on a large scale, our method provides us with a powerful tool to construct a synthetic population of good quality and with no confidentiality issues. Given the rise in computing power, micro-simulation models of populations are increasingly used to support decision-making in policy and fields such as epidemiology, demography, urban and environmental modelling e.g. , 8, 9)., 9.8, 9]An important part of individual based modelling is the construction of a starting population for the simulation . Next toAn important limitation of the availability of large amounts of information on individuals in a population is that such data constitute sensitive information, making privacy a primary issue. For open use, the disclosure risk of such data needs to be low, while the statistical structure should be as realistic as possible. Although in many countries data are available for selected researchers, this is usually under strict conditions in order to minimize the risk of disclosure of information on each single individual. Running a model on real population data therefore generally will only be allowed within the secure environment (computer system) of the trusted party that manages these data. Running simulation models within these systems is generally not very practical, for instance due to lack of portability of software or lack of sufficient computer power. Furthermore, in the spirit of open science, it is preferable to deliver micro-simulation models, including their data, as a public resource widely available.Construction of a synthetic population to be used outside a secured environment can overcome these difficulties. Such a population will reflect the structure of the available population data, but it will not represent real persons, though persons are constructed from the available population. In the remaining of this paper, such population will be referred to as synthetic population. Most papers on constructing synthetic populations focus on taking multiple random draws of individuals owning detailed personal information from a smaller size survey sample in order to obtain a larger synthetic population , 2, 11, This paper presents another methodology, in which regression models fitted on the original linked data are used to generate a synthetic population. We illustrate this for the case of a Dutch population targeted at chronic disease modelling. In chronic disease modelling, one needs a starting population with known socio-demographic characteristics, exposures to risk factors of diseases and presence of chronic diseases.The remainder of this paper is organized as follows: “The goal of the method is twofold: one, the protection against disclosure risk for individuals that make up the original dataset and second, to extract the available information from the original data for modelling purposes. Therefore, the synthetic population in constructed in a two-step procedure. The first step is carried out on microdata within the computer system of Statistics Netherlands (SN), under strict conditions regarding privacy and it boils down to constructing predictive equations that no longer contain information which can be traced back to a particular individual. In the second step these equations are used to drawn a synthetic population outside the microdata environment.The predictive equations in the first step were constructed as follows: starting from the original data set, a designated set of variables was selected with no identity disclosure risks: age, gender, region of residence  and level of urbanization, further referred to as the "seed variables". Their role is, among others, to create structure in the population, such as by means of stratification. Following the Statistics Nederland guidelines on disclosure risk, a requirement was to use a stratum sample size of minimally ten persons, that is, ten persons sharing the same combination of seed variables. Although there were a couple of strata with a lower number of individuals, the requirement was waved due to the insensitivity of the disclosed information . The number of individuals in each stratum was recorded and exported from the microdata environment for later stages of our approach.Within the microdata environment, the seed variables were used as starting point to build regression models in a variable-by-variable approach, for a set of designated, confidential variables, such as socio-demographics, lifestyle and presence of diseases. The estimated model parameters as well as their covariance matrices were also recorded and exported outside the microdata environment.In the second step, the frequencies of the seed variables strata and the estimated predictive equations were used, both outside the microdata environment, for the generation of a synthetic population.In the following paragraphs, each step is presented in more detail. “Appendix The targeted population is the population of the Netherlands at the 31st of December 2012, comprising 16 778 708 individuals (population size of the Netherlands on December 31st 2012). Our data sources were individual level, non-public, linkable microdata sets of Statistics Netherlands, made available under strict conditions regarding privacy issues. Virtually complete data were available on date of birth, gender, marital status, region of residence, level of urbanization, ethnicity, percentile group of household capital, source of income, percentile group of household income and household composition. Incomplete data on the highest achieved level of education were available for the non- institutionalized Dutch population aged 15 or older  2012 , 16. TheThe issue of missing data in the targeted variables of the Dutch Health Monitor 2012 due to the person-level non-response was addressed by means of multiple imputation, using the multivariate chained equation approach implemented in the mice R package . Five reIndividual probabilities of having coronary heart disease (CHD), stroke, diabetes or chronic obstructive pulmonary disease (COPD) in 2012 were calculated from prediction models using demographic data and data on drug reimbursement. These prediction models were developed using as outcomes individual data on hospital admission and primary care use. In short, the construction of the prediction model involved using LASSO regression model for variable selection followed by a regular regression, as described in Füssenich et al. .Incidence of lung and pancreatic cancer were available from the Netherlands Comprehensive Cancer Organization cancer register (IKNL), which records all individual cancer diagnoses in the Netherlands.k-th outcome variable, the predictors were the seed variables and the outcome variables ranging from 1 to k − 1; until the list of outcomes is exhausted.Taking a sequential approach, a series of prediction models are built as follows: for each newly targeted variable, a prediction model is fitted using as predictors only the seed variables and the variables included in preceding prediction models. The approach is initiated with a regression model for the first outcome variable which uses as predictors only the seed variables. So forth, for the This approach has the potential to ensure accurate statistical properties (e.g. to preserve the moments of distribution and the associations between variables) for the selected confidential variables, if the fitted models capture the distributions and associations correctly. However, models are always limited and bias might be introduced when the models do not capture all relevant relations or distributions. The sequential nature of the procedure implies that the inaccuracies in the prediction resulting from the first model will cause inaccuracies in all subsequent predictions. In order to optimize the predictions, the method uses with priority the variables available for the entire Dutch population, and within this set a ranking top-down is made following the decrease in magnitude of correlation among variables, ranking which dictates the order in the modelling sequence.As such, the first modelled variable is the main income source of the household, being the main driver of the social heterogeneity in the population, using the population defined in the configuration of the seed variables. Next two outcomes modelled were spendable household income and household capital, respectively, knowing that these can vary dramatically with the source of income. The predictive equations are subsequently extended by introducing successively type of household, household size and ethnic group. The reason for the introduction of the education variable rather late in the sequential modelling approach is the fact that it was the only variable of the nation-wide registry data with a large amount of missingness .After the nation-wide variables—with the exception of the presence of cancer—health and lifestyle information from the Dutch Health Monitor sample was added, such as BMI, smoking status and physical activity. Taking into account that lifestyle factors recorded in the Dutch Health Monitor sample were highly correlated with the two types of cancer, separated models for pancreas and lung cancer presence were subsequently fitted (in this order) using data on the entire Dutch population. In modelling these cancer types, lifestyle factors were accommodated by means of the missing indicator method , seen thGiven that diseases such as CHD, stroke, diabetes and CODP could be consequences of exposure to risk factors, they are modelled in this order in the remaining of the sequential procedure. These variables were expressed not as self-reported diagnosis registered in the Dutch Health Monitor study, but as predicted probabilities from an earlier model (see ), where In “Appendix From the population in the configuration of seed variables exported from the confidential environment the synthetic population of size 16,768,952  was constructed by randomly drawing from the predictive equations as follows. The first predictive equation was applied on the seed population and generated the first synthetic variable. Notably, these generated values do not contain real data for the targeted variable configuration. Next, a sequential simulation from the subsequent predictive equations was performed. The construction was limited to the ages 0–105 years, as this age range is generally accepted to be included in simulation models.As a method to investigate the utility of our approach, the statistical attributes of the synthetic population were compared to those of the confidential original population using univariate and multivariate statistics. For the univariate results, there were used the generated frequencies for categorical variables and the first four moments of risk factors distribution for continuous variables. For the multivariate results, there were used joint distributions stratified by age class, gender, smoking status and educational level. For this stratification, age was recoded as an eight-level categorical variable .Univariate results based on the original confidential population and the synthetic population are reported in Table In general, the frequencies of the synthetic data are close to those of the original data, although for the number of persons in the household and type of household the numbers were slightly different between synthetic and original. For lung cancer the prevalence was slightly lower in the synthetic population.To get an impression on the behaviour of the lifestyle variables for people older than 18 years, which were only available for a sample of the population, in Tables Comparing the moments, we see that the standard deviation of BMI is similar in the synthetic population and in the original data. However, skewness and kurtosis differ. As the model used assumes normally distributed residuals, skewness and kurtosis of the generated data are close to zero, while they are larger for the original data.To get an idea on how the predictions performed in a multivariate setting, figures for a selection of outcome variables are created stratified by age, gender, smoking and educational group. As smoking status is available for the Dutch Health Monitor sample only, again these figures contrasted the prevalence in the synthetic population with that in the Dutch Health Monitor sample. This multivariate approach comes with the advantage of displaying more accurate relationships due to the fact that by stratification variation due to the set of variables in strata is controlled for. Figures Figures Figures The objective of this paper is to develop a methodology for the generation of a synthetic population for application in chronic disease modelling, based on linked data at the level of individuals, household’s demographics and lifestyle characteristics in the presence of disclosure risk. A synthetic population amounting to the size of the total Dutch population of 2012 was created with realistic characteristics. Our method relies on the construction, in a sequential manner, of regression models for the distributions of individual attributes conditional on a set of determinants. It then uses these regression models to simulate a population by drawing from them. Each synthetic individual has a probabilistically assigned value for all but the initial determinants age, gender, region of residence and level of urbanization, the latter being used as in the original data.An important part of our data were virtually complete at the individual level . This yields, on the one hand, the benefit of dealing with minimum uncertainties in the modelling of these variables. On the other hand, model selection was time consuming, as the choice of potential models is large and running times on 16 million records are substantial, specifically when using complex models. As our approach needs parametric models, more automated prediction methods like random forest or other ensemble machine learning approaches could not be used. We settled for relatively simple models, assuming for instance normal residuals and only including a minimum of interaction terms by means of stratification.This means that the generated data reflected these assumptions, and the generate BMI data are close to being normally distributed, while in the original data they were not. Whether this is a problem will depend on how the synthetic population is further used. For uses as an initial population in micro-simulation of disease we do not deem this problematic. If the skewness of the original data needs to be reflected, the method can be easily adapted by using a model that better reflects such a feature of the data.An analysis of the goodness-of-fit of the synthetic to the true population using summary statistics and qq-plots showed that it was possible to achieve a high degree of accuracy for the set of first 7 variables (from age to ethnic group), given the availability of the true, complete population. For the next variables, based on the Dutch Public Health Monitor sample, validation of the results was difficult, as this sample displays a different composition than the whole Dutch population. For instance, in the synthetic population the number of former smokers was considerably higher and the number of never smokers lower than in the Dutch Public Health Monitor sample, despite the latter being younger. This means that the Dutch Public Health Monitor sample has a composition that deviates importantly from the general population. Therefore, the stratified comparisons we conducted are more informative. These comparisons depict several similarities, but some disparities were noted, which are probably due to insufficient use of interaction terms in the modelling. Further validation could be done using information from other sources , or by uFor prevalence of lung and pancreas cancer, we had population wide data, but models were partly dependent on variables (like smoking) that came from the Dutch Public Health Monitor sample, covering only 2% of the whole population. Lung cancer prevalence was slightly lower than it should be. This might be due to the way the model was constructed, which is vulnerable to residual confounding: the missing indicator method used implies that effects estimated for age or gender are only adjusted for smoking in the 2% individuals that participated in the Dutch Public Health Monitor survey. So, most of these effects will not be adjusted, while the construction method assumes they are adjusted. Using only the Dutch Public Health Monitor sample for fitting a lung cancer model would produce models that are less biased. However, given the low prevalence of lung cancer in this sample, such models would be very imprecise. Accounting for this discrepancy, for use in micro-simulation modelling, we recommend an additional post-calibration step, by increasing the probability of lung cancer during generation of the synthetic population with a factor that makes the prevalence equal to the population marginal.An important limitation of our modelling approach might be grounded in the fact that we did not include interactions in our models, apart from stratification. As a result, potential interaction become part of the error term, magnifying the unexplained variance. We have observed this in the modelling of household variables, where the relation between personal capital and income was not well described by a simple additive relationship, even when using splines. A more adequate approach could be achieved by means of non-parametric models like random forest, but exporting such models comes with disclosure risk and, therefore, are unfeasible in this context. However, as we experienced manual model selection as a very time consuming task, finding exportable models that automatically include or select important interactions would be a nice avenue to explore in further research.Due to the large amount of information, challenges were faced in each model as the fit could always be improved. For instance, in the extremes  of spendable income ranges, the relationship with personal capita is generally curvilinear, while in the middle-income range the relationship is linear. The explanation of this phenomenon at the lower end is partly that in some sectors (like agriculture) high investments (e.g. in land) are needed while income can be low. This relation could be the subject of further methodological and substantive investigations.We now constructed the synthetic population using the point estimates of the parameters. However, we also exported the covariance matrices of the parameter estimates, so it would be easy to use this to randomly draw parameter sets multiple times and construct sets of synthetic populations, each based on a random draw. These can be used to estimate the influence of the statistical uncertainty in the models on the outcomes of the micro-simulation.In our approach, all data apart from the seed variables are generated from fitted models. This might be too cautious with regards to disclosure risks. It would be interesting to see whether it is possible to develop a method which mixes real individuals with synthetic individuals and partially synthetic individuals in a manner that has no risk of disclosure.In this paper, we described the methods we used to construct a synthetic population meant for micro-simulation, based on population wide data liked to data of a large health survey. Although the constructed population does not reflect the original data exactly, we believe the reconstruction is close enough to reality to be suitable for use in micro-simulation. The method can be further improved by using models that include more interactions and transformations of dependent variables with non-normal residuals. It is surely superior to methods constructing initial populations that assume independence between variables. When marginals deviate too much from the available population marginal—mostly for outcomes variables employed later in the construction procedure—calibration can be added to adjust marginals, while maintaining the mutual relations between variables assumed by the models.