Background: Melioidosis is a bacterial infection which kills an estimated 89,000 people per year in tropical and sub-tropical regions, chiefly affecting the poorest. Diabetes is the primary risk factor, conferring a 12-fold increase in risk. Despite limited funding compared to other neglected tropical diseases, melioidosis vaccine development has generated several candidates for clinical development. CPS-CRM197/Hcp1 is a promising vaccine candidate developed at the University of Nevada, Reno which is due to enter a Phase I clinical trial in Oxford, UK in 2024. As we move closer to the possibility of field trials of a melioidosis vaccine, it is critical to work in parallel to understand perceptions toward a vaccine among those living where melioidosis rates are high. Reasons for vaccine acceptance versus hesitancy are complex, and include perceived risk of the target disease, concern about side effects, and above all trust in government, scientists, the pharmaceutical industry and other authorities.Methods: We will carry out a qualitative study in Ubon Ratchathani, Thailand, an endemic region for melioidosis, as groundwork for a potential future melioidosis vaccine efficacy study, and in the longer-term vaccine introduction. This study seeks to explore knowledge and attitudes in three main areas; 1) melioidosis disease, 2) vaccines, and 3) participation in clinical vaccine trials. In-depth interviews and focus group discussions will take place in five participant groups of different risks and exposure to melioidosis. Purposive, convenience sampling will be used, also snowball sampling to reach some participant groups. Sample size will be based on participant’s experience, to inform the line of enquiries of study, or until data saturation, expecting 66–90 participants across all groups.Discussion: The findings of this study will be written up and published in an open access journal, and will be valuable to inform future design of clinical trials as well as engagement and communications associated with future vaccine rollout. Burkholderia pseudomallei, resides in wet soils and rice paddies, and infects through cuts in the skin and inhalation of aerosolised bacteria. The clinical spectrum of melioidosis is broad but in the majority of cases infection gives rise to severe illness which is then difficult to treat. Mortality rates are highly variable by region and often > 50% in low- and middle-income countries (LMICs). Melioidosis infection has several risk factors, the strongest of these being diabetes which increases the risk of infection 12-fold. Other risk factors include older age, kidney or liver disease and excessive alcohol consumption. Hopes are high for the development of an effective vaccine; a melioidosis vaccine offering a good degree of protection delivered to diabetics is likely to be a cost-effective intervention.The causative agent of melioidosis, bacterium. A promising subunit candidate vaccine has been developed at University of Nevada, Reno (CPS-CRM197/Hcp1) with plans for a Phase I clinical trial in Oxford, UK in 2024 to determine safety and immunogenicity in healthy adult volunteers with and without diabetes. This trial of a melioidosis vaccine in humans will be a landmark in the struggle to combat the devastating impact of this disease, and it is hoped will pave the way for the testing of other promising candidates. Providing the safety profile of the vaccine in humans is acceptable and immunogenicity is demonstrated, further studies will seek to replicate immunogenicity in populations in endemic regions, and assess vaccine efficacy.Several vaccine types have been explored in animal models for potential to prevent melioidosis, and numerous candidates have demonstrated some degree of protection. With established infrastructure to support research in the area, Ubon Ratchathani is a strong candidate site for a phase II melioidosis vaccine trial. Local community engagement with the research from an early stage is critical to the success of a clinical trial. The trial design must be appropriate to the local setting, and consider relevant cultural, religious, political and environmental factors. In Ubon Ratchathani, gaining insight into the perspectives of people who could be eligible to take part in a melioidosis vaccine trial on the topics of vaccination, melioidosis, and taking part in research, will help to identify the needs of potential volunteers.Site selection for a phase II vaccine efficacy trial takes into account a range of factors, including the size of the population at risk, local incidence of the disease, and infrastructure to support clinical trial activities. Thailand is endemic for melioidosis, with a high incidence documented over several decades in the region of Ubon Ratchathani in Northeastern Thailand. These studies uncovered factors connected to vaccine hesitancy, for example low education levels and the presence of existing health conditions in older adults, and have identified social influence by family, peers and healthcare providers as a strong driver in decision-making around vaccination. Studies of attitudes toward COVID-19 vaccination in Thailand report relatively high rates of hesitancy to be vaccinated, but connectedness of attitudes toward COVID-19 vaccination and vaccination against other diseases are to be explored. At the level of the whole country, a recent (2016) analysis suggests that feelings about vaccination in Thailand are amongst the most positive internationally, with attitudes towards the importance, safety, and efficacy of vaccination in general more favourable than on average across the 67 countries included. However just one country ranked higher in the proportion of respondents expressing a negative reaction to the statement ‘Vaccines are compatible with my religious beliefs’, highlighting that cultural and religious factors may be of particular importance in driving the willingness of adults in Thailand to consider undergoing vaccination.Once a vaccine is licensed, widespread acceptance is crucial in order to fully realise the potential benefit in prevention of disease, and maximise vaccine cost effectiveness. Reasons for vaccine acceptance versus hesitancy are complex and vary in each context, they include perceived risk of target disease, concern about side effects, and above all trust in government, scientists, the pharmaceutical industry and other authorities. To date, qualitative studies have provided insight into public knowledge of coronavirus 2019 (COVID-19) and influenza, and attitudes towards vaccination against these infections in ThailandThe aim of this study is to gather the perspectives of key population groups relevant to clinical trials and rollout of melioidosis vaccines, on the topics of melioidosis, taking part in clinical trials for melioidosis vaccines, and vaccination in general and against COVID-19 specifically. The study will explore beliefs, perceived risks, benefits and factors influencing position of vaccine acceptancy/hesitancy, among diabetes patients, patients’ relatives and persons with risk of exposure to melioidosis in Ubon Ratchathani.The findings of this study will provide important insight into motivations for taking part in clinical trials as well as associated concerns, which will inform the feasibility of future trials and facilitate sensitivity to the local setting in the study design. Healthcare providers involved in promoting vaccination among individuals with a high risk of melioidosis will benefit from this information to design suitable interventions and treatment in the future.This study will be carried out within the Ubon Ratchathani Province, Thailand, in four districts with high cases of melioidosis, while maintaining balance with districts with diabetic patients  .Ubon Ratchathani is located in the lower part of Northeastern Thailand, bordering Cambodia and Laos PDR. The general topography of the province include flood plain , alluvial plain, peneplain, and piedmont. Two main rivers flow through the centre of the province towards the Mekong River. To support agricultural activities, there are many irrigation canals and sub-canals spread across the province. The rainy season is from May to end of October, marking the farming and growing season. The main occupation of the Ubon Ratchathani population is in the agricultural sector, also over half of total province area is for agricultural purposes , including paddy fields (47.85%).This study is an exploratory research study, utilizing qualitative research methodology in data collection, including in-depth interviews (IDIs) and focus group discussions (FGDs). Interview notes and field notes will be taken during or after data collection sessions to record any other observations an audio recorder is unable to capture. Participants in this study will be invited to share their thoughts in semi-structured interviews and/or focus group discussions, to approach intended outcomesQuestions in topic guides are designed to ascertain experience and levels of awareness of melioidosis, thoughts and opinions on undergoing vaccination and taking part in a melioidosis vaccine trial, as well as the basis for these. A topic of much relevance currently, attitudes towards vaccination against COVID-19 will also be explored as part of the discussion on vaccination in general.Primary outcome: An account of the views and perceptions of diabetes patients in Ubon Ratchathani on the topics of melioidosis infection, vaccination, and taking part in clinical trials for melioidosis vaccines.Secondary outcomes:1) An account of views on vaccination in general including perceived benefits and risks, and the enabling factors and barriers. An account of views on COVID-19 vaccination specifically, the general feeling of the community regarding COVID-19 vaccination, and assembled concerns.2) An account of knowledge and understanding of the cause, severity, diagnosis, and symptoms of melioidosis. An account of knowledge and understanding of melioidosis risk factors, and preventative measures for melioidosis including vaccination.3) An account of attitudes towards taking part in clinical trials of melioidosis vaccines including the risks and benefits, and the nature and sources of concerns and drivers.Purposive, convenience sampling techniques will be mainly used to identify research participants for this study, with occasional snowball sampling technique for specific participant groups. As a qualitative study, sample size will be based on experience of participants, to inform the line of enquiries of study, or until data saturation. Approximately 26 IDIs will be conducted, and more if needed. Approximately eight FGDs will take place, with between five and eight participants in each . Therefore, the total number of participants across both data collection methods is estimated to be between 66 to 90 . The stuGroup 1 and 2 will consist of diabetes patients, and present or former melioidosis patients between a) 20–60 years old, and b) over 60 years old. They will be identified through existing records held at primary care units for diabetes clinic attendance, and existing records of melioidosis patients.Group 3 participants will be villagers living in the endemic area, with exposure risk to melioidosis from occupation or livelihood, and interest to take part in the study. The potential participants will be identified by local/area key persons, for example village chief, local healthcare workers, village health volunteers.Group 4 participants will be a caregiver or main supporter, relative or nonrelative, of a patient with diabetes or melioidosis, and will be identified by participants in groups 1 and 2. Researchers will contact potential group 4 participants only with the agreement from the corresponding participant of group 1 or 2.Group 5 participants will include healthcare personnel, local experts, community leaders including village chief, and elder with in-depth understanding of the study site context. The work role, or area of expertise, or experiences of healthcare personnel and staff would be taken into consideration.Most participants will take part in a single interview, although if needed a follow up interview may be conducted. Permission for each follow-up interview will be sought from the participant. The choices and decisions of participant will be respected. For each case, the study team will contact participant via phone to seek their willingness and availability for follow-up interview. An alternative district will be identified by the Principal Investigator (PI) and study team should recruitment be unsuccessful at any of the sites outlined inParticipants for all groups aged 20 and above, with ability to provide written informed consent and able take part in the interviews.Persons that are not able to provide written consent, unfit and unable to take part in the interviews.This study will recruit healthy volunteers, those apart from diabetes and melioidosis patients, who are villagers, and farmers with risk of exposure to melioidosis in their work or daily lives, to triangulate the views and perspectives on vaccine attitudes, and participation in clinical trials among villagers living in melioidosis endemic area. The study team will seek to minimise disruption to participant’s livelihoods in the arrangement of interview times and venues. This study will include diabetes and melioidosis patients aged above 60 years old. Both diabetes and melioidosis are considered chronic conditions due to the need for prolonged treatment. Half of melioidosis patients have underlying diabetes, and the majority of patients diagnosed with diabetes are elderly. Including them in this study is important to ensure that perspectives of population groups at the greatest risk of melioidosis are represented.All participants have the right to withdraw from the study at any point without having to provide reason. If data has been collected from a participant requesting to withdraw, they will be asked if the data collected can be used for analysis or not, and the participant’s decision will be respected. At any time, if a participant wishes to stop an interview the participant’s decision will be respected. Should a participant become or feel distress from taking part in this study and interview, consultation with PI and co-investigators will be conducted. This is to ensure that appropriate referral is arranged with participant’s knowledge, and consent is obtained for any additional supports in area of need(s).Participation of this study is purely voluntary. There will be no negative consequences should they decide to stop their participation or withdraw from the study after they have decided to participate.Extended data). Discussion topics will remain within scope of the objectives. Interviews (both IDI and FGD) will be carried out in Thai, and in Northeastern Thai dialect when necessary. IDIs will be conducted in a private room at a Primary Care Unit (PCU) or in an open space where the participant(s) feel comfortable to freely express their viewsThis study will use two types of interviews (IDI and FGD). The discussion will be led by study team members trained and experienced in these interview approaches, and in accordance with a topic guide  or not preferred by the participant. Consent will be obtained before interview date.FGDs will last between 1 and 1.5 hours, with participants to take a short break on request.Focus group discussions are best conducted in-person to stimulate discussion from participants with diverse backgrounds and views. If necessary, group sizes will be adjusted for compliance with COVID-19 measures, if relevant. Consent will be obtained before interview date to confirm participant’s interest in taking part in the study and interview. The venue will be chosen to meet the requirement of group activity with strict observation of physical distancing, body temperature screening and mask wearing throughout the interview. Researchers and participants involved in FGD must present a negative COVID-19 test result e.g., antigen self-test kit (ATK). The test should be taken in the 24 hours before the scheduled interview, with consideration and compliance of recommended measures from provincial and district public health office.All interviews (both IDIs and FGDs) will be audio recorded to ensure that discussions are properly captured.est. GBP12), for one interview lasting between 45 minutes to 1.5 hour to compensate for their time to take part, traveling fees, and loss of income for the period which they took part in the interview. Participants will be provided with refreshments at the interview venue.Compensation will be provided to participants taking part in IDIs and FGDs. Each participant will receive THB500 . Audio files will be kept until transcribed and analysed, transcribed interviews files will be kept in secure servers with a proper backup system. The study team will de-identify participants’ information to maintain confidentiality.The data produced will consist of audio recordings, transcripts, and field notes. All audio files will be transcribed and translated verbatim into English. The interview and focus group discussion transcripts, including relevant text files, will be managed usingThe analysis will include content analysis, narrative analysis, and thematic analysis, following with open coding to find and group the emerging themes. The coding will begin as early as the first few transcriptions are ready. Any language ambiguities, likely from Northeastern dialects, will be discussed thoroughly with local co-investigators who speak and understand the dialects. Interview notes and field notes will also be taken into consideration for formal content analysis, which could shape the data and validate the data collected from that specific interview or focus group discussion. Axial coding, or second passing coding will be done with the wider team which include the main investigators.The University of Oxford is the data controller with respect to participants’ personal data, and as such will determine how the personal data is used in the study. The University will process the personal data for the purpose of the research outlined above. Research is a task that is performed in the public interest.MORU Data Sharing Policy.Access to data which are recorded audio files, interview notes, field notes and interview transcripts and photographs will be granted to authorised representatives from the sponsor, host institution, Ethics Committees, regulatory authorities for monitoring and/or audit of the study to ensure compliance with regulations. Data collected for this study will be under the custodianship of Mahidol Oxford Tropical Medicine Research Unit. The data will be de-identified. De-identified data may be shared with other groups of researchers upon reasonable request, in accordance with the currentResearch ethics: This is a minimal risk study posing very low risk. There are no medical or behavioural interventions to participants. The main ethical issues are related to privacy and confidentiality. The interview and focus group discussion venues will be private and comfortable spaces for all participants. Care will be taken to maintain privacy during the audio recording of data collection processes, with both individuals and group participants.Research ethical approval: This study has been granted ethical approval from the Oxford Tropical Research Ethics Committee (OxTREC), reference number: 533-22 (dated 19 July 2022), and the Ethics Committee in Human Research of Sanpasitthiprasong Hospital, study identifier code 040/65C (dated 21 December 2022).Consent: Main co-investigators  are responsible for seeking and obtaining written informed consent and will lead this process with the assistance of local co-investigators . Local co-investigators will provide necessary interpretation between Thai and local dialect Thai. No assent will be use in this study.Confidentiality: Participants will be informed in prior to data collection that the session will be audio recorded and transcribed. The transcripts will be de-identified for publication and for data sharing, if any. All study team members will adhere and ensure that participants’ confidentiality is well maintained.Participating in an interview may result in loss of privacy, information provided during interviews will be recoded but names or any personal information will not be used in any reports and all personal information will be de-identified to protect participant’s privacy.Participant can skip or not answer questions that they do not feel comfortable answering.Any mention of any persons during an interview will be anonymized to protect their identity and privacy.Dissemination policy: The results of this study will be published in an open access journal. The findings will inform the feasibility of future vaccine studies, as well as identify perceived risks, benefits, or other ethical and biological concerns regarding vaccine studies, clinical trials, and involvement of human participants. The dissemination of this research will support the design of future research to be more responsive and sensitive to the local context and setting.th May 2023 the number of participants recruited across all groups is 32.Data collection started on 20th February 2023 and is on-going. As of the 14 Thank you for the opportunity to review this manuscript outlining the methodology for a qualitative research study on the attitudes of people in northeastern Thailand towards vaccines, melioidosis, and clinical trials. The rationale for this work is clearly articulated. A phase I clinical trial for a subunit vaccine for melioidosis will commence in the UK this year, with phase II efficacy studies in endemic areas likely to follow. Importantly, design of such an efficacy study should be appropriate to the local setting. This study will help to identify the needs of potential volunteers in an endemic area which is potentially suitable for such a trial. The study design is appropriate. The study will include 66-90 participants comprising people living with diabetes (a major risk factor for melioidosis), people with previous melioidosis, support persons for the former two groups, people at risk of melioidosis exposure, and experts and community leaders. In depth interviews and focus group discussions will be conducted to investigate knowledge, understanding and attitudes towards vaccination , melioidosis, and clinical trials for a melioidosis vaccine. The questions included in the Topic Guide (Extended data), and the approach to recruitment, consent, participant withdrawal, data management, privacy and confidentiality are appropriate. In the Introduction there is a section outlining factors associated with vaccine hesitancy - including trust in authorities, education levels, and cultural and religious factors. It isn't clear from the manuscript whether or how these factors will be explored in the study. It also isn't clear whether the analysis will look at whether there are particular trends among the different groups of study participants outlined above, and whether attitudes vary among people with different demographics such as age, gender, occupation, or region. I would recommend that this be clarified. Overall, the planned research forms an important component of melioidosis vaccine phase II clinical trial design, and will ensure that such a study is most likely to meet the needs of trial participants - and ultimately those who stand to benefit most from a vaccine to prevent melioidosis.Is the study design appropriate for the research question?YesIs the rationale for, and objectives of, the study clearly described?YesAre sufficient details of the methods provided to allow replication by others?YesAre the datasets clearly presented in a useable and accessible format?Not applicableReviewer Expertise:Genomic epidemiology of infectious diseases, including melioidosisI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. The study aims to gather the perspectives of key population groups relevant to clinical trials and roll out of melioidosis vaccines. To explore the beliefs, perceived risks, benefits, and factors influencing acceptance among diabetes patients.  INTRODUCTION - This section contains adequate background to the study. Still, it would also benefit from a mention of reasoned action as attitudes and subjective norms contribute to intention and behavior (acceptance of vaccine).  The last sentence of the Aim could include designing a context-specific intervention in close partnership with the community.  STUDY DESIGN - this is adequate.  PARTICIPANTS - Exclusion criteria based on not being able to provide written consent could be re-considered as verbal consent and thumb print is also an option for consent. Not much mention is made of in the study of consideration of gender. This is important as attitudes can be perceived from a gendered perspective. It would also be important in the analysis since this is a qualitative study to look at gender.  GROUP 4 - the participants in this group should read primary care giver. GROUP 5 - this should also take into consideration the role of community leaders in influencing attitude change and being co-participants in designing the context specific intervention.  CONSENT - as part of eliciting consent, also include Participant Information Sheets that provide participants with all the information required for the study to enable them provide adequate consent.Is the study design appropriate for the research question?YesIs the rationale for, and objectives of, the study clearly described?YesAre sufficient details of the methods provided to allow replication by others?YesAre the datasets clearly presented in a useable and accessible format?Not applicableReviewer Expertise:Qualitative research, Clinical trialsI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


The adverse environmental impacts of food production, the ill-health resulting from excess consumption and malnutrition, and the lack of resilience to the increasing number of threats to food availability show that the global system of food provision is not fit for purpose. Here, the causative flaws in the food system are identified and a framework presented for discovering the best ways to eliminate them. This framework is based upon an integrated view of the food system and the socio-economic systems in which it functions. The framework comprises an eight-point plan to describe the structure and functioning of the food system and to discover the optimum ways to bring about the changes needed to deliver a sustainable food future. The plan includes: priorities for research needed to provide options for change; an inclusive analytical methodology that uses the results of this research and incorporates acquisition, sharing and analysis of data; the need for actions at the local and national levels; and the requirements to overcome the barriers to change through education and international cooperation. The prospects for implementation of the plan and the required changes in the outcomes of the food system are discussed. This was enabled by the Green Revolution and its aftermath in which increases in crop yields are achieved through development of new varieties of crops and the deployment of chemical fertilizers, pesticides and innovative farming technologies including irrigation and mechanization . SimilarAn assumption, one that has plagued other human activities, is that the Earth resources supporting the food system and the capacity of the Earth to absorb its impacts are both limitless, setting in place the first flaw: an environmentally unsustainable production system which causes greenhouse gas (GHG) emissions, pollution of land and water, depletion of groundwater, clearing of grasslands and forests and reduction in biodiversity. It is also seen as a factor in the emergence and impact of zoonotic disease such as COVID-19 . Hence, There are other flaws. The quest for increased yield inevitably meant that only a small number of crop species (and genotypes therein) are used, mainly rice, wheat and maize. The decreased diversity of crop plants increases the risk of disruption from pests and disease, creates genotypes highly dependent on the above inputs, and impinges on the culture, health and social economics of many areas of the world —the secoA further series of flaws arise from the complexity and globalization of the global food system . VulneraComplexity and globalization also have consequences for the producers of food. Farmers may struggle to adapt to changes in costs or contracts, while the same pressures may create poor conditions for agricultural workers, which in high-income countries are often temporary migrant workers. Similarly, resource-intensive agriculture in low- and middle-income countries for export to urbanized high-income countries may force indebtedness, resource depletion and environmental impacts that are not associated with domestic consumption.. 2The adverse outcomes arising from these multiple flaws in the global food system can be exacerbated by a range of often uncontrollable external threats—natural disasters, extreme weather events, new trade deals and regulations, economic upheavals and political actions  12]. Th. Th12]. . 2.1Perhaps the most important threat to food production is climate change, including both extreme weather such as storms, flooding, heat and drought, as well as sustained changes in temperature and rainfall . Climate. 2.2A major threat arises from restrictions upon the availability and full utilization of fertile land for agriculture . This ha. 2.3The food system is sensitive to a variety of external socio-economic factors, from political interventions, logistical problems and global catastrophes, such as the COVID-19 pandemic and the Ukraine war . Such di. 3While the current trend is often to address the specific effects of flaws in the food system (often unsuccessfully), here we contend that the imperative is to correct the flaws themselves—a root and branch change in the way we produce, distribute and consume food in order to deliver the better outcomes humanity needs . Such reIt has been suggested that viewing the food system as a 'food ecosystem’ provides the right theoretical context . Indeed,. 3.1Research has traditionally separated the various aspects of the food system, with individual sectors setting their own priorities and objectives. It is vital that an integrated, system-wide approach is taken, so research agendas are established within the food ecosystem context, projects being co-designed by partners across disciplines. Many reforms of the food system have been discussed but most are untested and unproven within this broader view. Research is needed, principally in universities and research institutes but not in isolation: collaborations with local, national and international agencies and the private sector are essential. Funding bodies, whether governmental or charitable or commercial, need to coordinate their activities. Below are listed five key areas of research. It is imperative that they are not seen as separate but linked together in ways that provide interdisciplinary research and enable integrative solutions and policies to emerge. 3.1.1.Integrated thinking is needed to establish priorities for improvements in agriculture, ensuring that biologists, biotechnologists and agronomists work together—a regenerative agriculture that combines state-of-the-art plant and soil science with advanced agronomic technologies including robotics and remote sensing. Exploiting advances in plant physiology, gene editing and conventional breeding, new crop varieties can be developed that have increased yield, are more resilient and adaptable to climate change, require less fertilizer and water, and which can help preserve soils and increase carbon capture . This qu. 3.1.2Synthetic food could potentially totally transform the food system, eliminating most environmental impacts . However. 3.1.3Building on recent advances –10,12,21. 3.1.4The food system is central to political, cultural and economic activity, meaning that issues outside the supply chain itself must be considered. Research is needed to help meet two objectives. Firstly, we need to understand how reforms of the food system can provide not only sustainable and resilient food security but also protect culture and livelihoods. These reforms need to comply with international trade agreements and environmental regulations, but also the ambition of nations to be more self-sufficient in food. What kinds of new business models can meet these aims while ensuring profitability and stability? What interventions are needed by governments to drive these reforms? Secondly, we need to better understand the cultural, economic, environmental, political and social impacts of reduced availability of affordable food, and how to offset them. Some of these are well known and thoroughly documented, such as increased hunger, malnutrition and ill-health. Others are a consequence of the increased costs of food and include reduced business profitability, trade imbalance and suppressing growth of the wider economy. There are many social impacts—unemployment, increased inequality, civil unrest, migration and conflict between nations. As recently discussed with respect to climate change impacts, economic, political and social changes are hard to quantify and accurately estimate, adding to the potential risk . Again, . 3.1.5Agriculture uses approximately half of the Earth's habitable land . New app. 3.2Outcomes of research then need to feed into an effective science–policy interface . It is iMany barriers must be overcome, particularly the problem of fragmentation. Fragmentation arises for many reasons. It is easier to consider a single process such as a supply chain or part of a supply chain, and it is often seen to be more economic for businesses. Organizations such as government departments or international agencies often prefer to deal with problems within narrow boundaries because it is simpler and enables retention of control and power. The need for integration is often not thought necessary, and there are frequently no mechanisms through which integration can be realized. Sharing and collaboration may contravene competition laws or confidentiality, either personal or corporate, or may be commercially sensitive. Further, this kind of cooperation may be countered by the policies of individual enterprises or governments who instead pursue activities which then exacerbate the flaws in the food system. Of particular concern is that there is often seen to be no advantage to the various participants to collaborate or to share information in the way needed.In the following sections, the requirements that need to be met to establish the MAVS protocol for operation of the food science–policy interface are listed.. 3.3It is necessary to unambiguously define and distinguish resilience and sustainability. A resilient food system is not always sustainable—for example, a plan to increase domestic food production through extending intensive industrial agriculture may increase resilience but may not be sustainable. Equally, it is important to define sustainability in its broadest sense and not just in terms of environmental impact —for examThe next step is to devise metrics of sustainability and resilience. Discovering a successful intervention in the food system first requires reliable, rigorous and meaningful metrics of the multidimensional outputs of food provision: how exactly do we measure when a process or an activity is sustainable; how do we reliably offset sustainable and unsustainable activities (including trade-offs and compromises); how do we measure the scale up from individual actions to national and global dimensions; and how do we quantify the various external criteria defining a successful sustainable food system, preservation of biodiversity, human health and well-being, and humanity's harmony with nature? The difficulty of answering these questions is exemplified in a recent study of the plan for expansion of bioenergy use in the EU, and its impact on regional and international land use for agriculture, biodiversity protection and carbon storage goals . The difThere are already initiatives striving to devise useful metrics of the environmental and health impacts of foods. Indices combining health and environment are being used to construct dietary choices . Large n. 3.4Food system reform requires the collection, analysis, synthesis and validation of large amounts of evidence and data obtained from, and shared between, a wide variety of sources within the food system. The revolution in the production and analysis of data provides an unprecedented opportunity to advance the development of integrated food systems approaches. It is now feasible to use data to describe in fine granular detail the mechanics of food systems, the human behaviours that drive them, and their socio-economic consequences. Within the global food system there are a huge number of different supply chains, agricultural practices and food delivery processes—within these are key determinants of what is most efficient, sustainable and resilient. Through data science including AI it will be possible to develop of holistic, system-wide maps to describe all these features of the structure and function of food systems.There are many barriers to break through to establish the trust necessary for this level of data use , particuThere is already a lot of activity around this issue in other sectors, within the EU and USA . The hea. 3.5There are now much-improved opportunities to use AI and digital modelling techniques to predict the behaviour of complicated systems. In biological and biomedical research, profound breakthroughs are enabled, from predicting the structure of proteins from their primary amino acid sequences to understanding how multiple genes control cell function and disease states. In climate science, more accurate predictions of the effects of GHG emissions on global warming and changing weather patterns are enabled. Increasingly refined models have been used in formulating policies to deal with the spread of COVID-19. These techniques enable the use of data to model food systems and facilitate prediction of their resilience and the impact of future trends.The objective would be to create digital twins of the food system . These w. 3.6The transformation of the food system depends on people—consumers, employees in food businesses, farmers, members/advisors of NGOs, international organizations and governments. Education in all aspects of the sustainable society, and specifically related to the food system, underpins everything discussed in this article. It is important to find ways to promote an understanding of evidence and facts, of how the scientific process works so people not directly involved in the food system can make informed choices and influence both government and business, becoming what have been described as competent outsiders . CommuniThese requirements vary across different countries. In some, improving gender equality in education is a priority: there is evidence that equal access by women to education, training, resources and finance together with equal rights and status can bring about positive changes in the food system, given the dominant role they play . In otheThe food system has undergone many changes in the right direction: increased availability of meat-free products, improved animal welfare, awareness of food waste and unnecessary packaging and so on. The extent to which these changes result from better-informed consumers making altered food choices, or from public or political pressure on food companies (and their shareholders), or from these companies recognizing the need for change and identifying new ways to increase profit is currently unclear, but in all cases could be the outcome of better ‘education’.. 3.7What needs to be avoided is creation of new vast centralized top-down bureaucratic bodies attempting to impose change universally. Collective action agreed across all countries is needed because all nations share responsibility for global food security and the functioning of global supply chains. However, food security is not the same type of issue as climate change—national action cannot alter the climate of that nation specifically, unlike interventions within the food system, where in theory effective changes can be initiated at the local or national levels. Indeed, it has been argued that food system reforms are best approached initially from the national perspective . Thus, t. 3.8National governments must be the principal agents for compliance, setting objectives and priorities for action. There are many possible mechanisms, ranging from voluntary to enforced and comprising persuasion, incentives, rules and penalties. Much can be learned from exploring the problems involved in making the changes needed to combat climate change. It has been argued that new financial regulations are needed to enforce disclosure of climate risks . However. 4It is broadly agreed that the food system needs transformation if it is to deliver global food security while removing its contribution to GHG emissions and helping humankind stay within planetary boundaries. As noted above there is already evidence of positive changes within the food system. But these are still limited in scale and scope. Various negative forces delay and subvert fundamental change within the food system —nationalThere is evidence across countries and societies of increasing awareness of all aspects of sustainability and of the need for change , and as


Positive ethnic choice effects, namely a higher likelihood of attending more demanding educational tracks among students of immigrant origin compared to their native peers, are observed in many countries. Immigrant optimism, and thus the striving for upward social mobility, is seen as a key mechanism for explaining ethnic choice effects. However, research on this topic often ignores gendered educational pathways and trajectories. Based on data from German-speaking Switzerland on two school-leaver cohorts, our interest is on whether ethnic choice effects are observable for both female and male students whose parents were born in the Balkans, Turkey or Portugal. In addition, we examine the extent to which aspirations contribute to explaining ethnic choice effects for both genders. To disentangle the direct effect of a migration background and the mediating effect of aspirations on educational attainment at upper secondary level, we apply the reformulated KHB method in our analyzes. Overall, our findings indicate that migrant women have made up ground on their native peers between the two school-leaving cohorts, contributing to the widening of the gender gap within the migrant group of interest. Of particular importance, however, is our finding that ethnic choice effects are observed only for men, while we do not observe any evidence of ethnic choice effects in the sample of women. Consistent with previous findings, our results show that aspirations mediate part of the ethnic choice effect. Our findings support the consideration that the room for ethnic choice effects is related to the proportion of young men and women striving for academic education, with gender differences in this regard being particularly pronounced in education systems with a high degree of vocational specificity. The set of educational alternatives is linked to the type of school attended during compulsory schooling. Based on institutional regulations, admission to academic tracks is granted to students who have attended a school type with advanced requirements or a pre-gymnasium, and have achieved a required grade point average or have passed an entrance examination. Students at academic tracks  earn a higher education entrance qualification, whereas students in the VET system acquire occupation-specific skills in one of about 240 fields, which mainly prepare individuals for labor market entry. The transition to upper secondary education is decisive for educational and occupational career prospects since the permeability between academic and vocational tracks is low . Since women on average show a markedly higher transition rate to academic tracks than men, the room for ethnic choice effects within the population of women is likely to be limited. Given that female students from the ethnic groups of interest have made up ground considerably on young women from the majority population in terms of educational attainment within the period under examination, we expect to observe an ethnic choice effect within the older school-leaver cohort, but at most weak effects for female migrants within the younger cohort (Hypothesis 2). For men, however, the relative proportion enrolled in academic tracks is remarkably low and did not change substantially between the two cohorts. In this context, we expect the striving for upward social mobility to result in positive ethnic choice effects for men in both cohorts (Hypothesis 3). Finally, we assume that part of the ethnic choice effects—if observable—is mediated by students' aspirations for upward social mobility (Hypothesis 4).On the basis of the recent developments in migration to Switzerland described above, and previous findings by Tjaden and Scharenberg  as well Our analysis is based on data from two school-leaver surveys. We use data from the first TREE cohort, which is a nation-wide Swiss panel study of young people born around 1985 who participated in PISA 2000 and left compulsory school in the same year . A small number of youth who were attending non-mandatory bridge year courses at the time of the survey are excluded . We impute missing information through chained equations  15 months (DAB) to 2 years (TREE) after leaving compulsory school.Regarding the underlying mechanism of the ethnic choice effect, and in line with status position theory  and the highest socio-economic status (ISEI-08) within the family. To account for prior achievement we consider students with observed information on the school type attended from Grade 8 in the case of the DAB sample, while the TREE sample includes students from Grade 9. The grade point average (GPA) in mathematics and language (German) are used to control for school performance. We differentiate between the school type with basic requirements, the school type with advanced requirements, and the pre-gymnasium. Grades in Switzerland are usually ranked from 1 to 6, with 6 being the highest possible grade and 4 the minimum requirement to pass. Grades are used in X variables, including the mediator variable Z , using binary logistic regression. Based on this model, the latent index xb is saved and used as a new dependent variable using ordinary least squares (OLS), while covariates and mediators are included stepwise to estimate the extent of mediation. We present bootstrapped standard errors of selected coefficients of nested models, as well as estimates and bootstrapped standard errors of the indirect effects and the percentage mediated.While stratifying by school-leaver cohort and gender, the focus is on ethnic choice effects regarding enrolment in academic tracks . As proposed by Breen et al. , we use Before turning to the multivariate analysis of the ethnic choice effects, we briefly outline some descriptives for the two cohorts see . In lineNext, we discuss our findings related to gendered ethnic choice effects. Hypothesis 1). More concretely, our results reveal ethnic choice effects in the case of men in both cohorts. The positive association of young men from the ethnic groups of interest with the propensity to enter an academic track is stronger in the older cohort (TREE). This is in stark contrast to the findings for women for whom ethnic choice effects are not evident at all. Although the coefficient for women in the DAB sample is positive, albeit not significant, the coefficient for women in the TREE sample is negative even after controlling for social origin and the indicators of school type and school performance. While we expected this result for men (Hypothesis 3), we had also assumed that an ethnic choice effect for women in the older cohort would be present (Hypothesis 2).In Model 2, we additionally control for social origin, the school track attended at lower secondary level and school performance. As expected, we find gender differences in regard to the observable ethnic choice effects .In Model 3, we additionally include the mediator variable: the aspiration for upward social mobility. Since we do not observe ethnic choice effects in the case of women, we discuss only the results of the mediation analysis for men. The estimates of the indirect effects and percentage mediated by aspirations are provided in While aspirations reduce the direct effect of the migration background on the propensity to attend an academic track by 8% in the older cohort (TREE), about 40% of the direct effect is mediated by aspirations in the younger cohort (DAB). However, the apparently low contribution of aspirations to the explanation of the ethnic choice effect in the TREE sample cannot be attributed to the fact that aspirations in this sample were measured only a few weeks before the end of compulsory schooling. Although it is theoretically plausible to assume that experiences in the form of missed entrance exams lead to a cooling-out of career goals and aspirations Clark, , i.e., aIn the present study, our focus is on the presence of ethnic choice effects in German-speaking Switzerland among young men and women whose parents were born in the Balkans, Turkey or Portugal. These ethnic groups achieve a significantly lower socio-economic status compared to the majority population (Gomensoro and Bolzman, As an extension to the current state of research, we operationalise the aspiration for upward social mobility as the difference between the socio-economic status of the family and the desired occupation of the child. In this way, and in line with status position theory (Keller and Zavalloni, Our contribution highlights that ethnic choice effects for specific migration groups are not necessarily observed for both men and women. While existing research reveal ethnic choice effects at different educational levels, our findings underline the importance of analyzing ethnic choice effects separately by gender. This should be all the more important, the more gender-specific the educational pathways within an education system are. Our results indicate that the room for ethnic choice effects is related to the relative proportion among men and women striving for academic education. We expect similar results in other education systems characterized by a high degree of vocational specificity, as these systems often feature a high degree of gender segregation at post-compulsory level. In such a context, we do not consider it meaningful to refer to ethnic choice effects for an ethnic group as a whole when, in fact, the variation between genders in regard to the outcome of interest is high.per se differ in other education systems by gender. Nevertheless, we strongly encourage scholars to replicate our findings with reference to migration groups in other countries for which gender-typical educational trajectories are characteristic.Our findings reveal the importance of conducting analyzes related to ethnic choice effects stratified by gender. We observe ethnic choice effects in both cohorts in the case of men, whereas such effects are not evident in the case of women. If we had conducted the analyzes without stratifying by gender, we would have observed ethnic choice effects in both samples, which is in line with previous findings (Tjaden and Scharenberg, With regard to the gendered ethnic choice effects reported here, we would like to emphasize that our results do not imply that young women from the migration group of interest are less successful in the education system than their male peers. On the contrary, young women from this migration group were able to catch up substantially with women of the majority population within the period considered. This has contributed to the widening of the gender gap within the migrant group of interest.Finally, in terms of the limitations of our study, we faced the problem of many studies comparing majority and minority ethnic groups: The sample size of minority students limits the possibilities for analysis. In the context of tracked education systems such as that in Switzerland, it would be beneficial to further restrict the analysis sample to students from the cognitively more demanding school types at lower secondary level, who show a higher transition rate to an academic track than students from the school type with basic requirements. However, this was not possible due to sample size limitations as is the case for separate analyzes by ethnic origin. Although we have referred to the concept of immigrant optimism and used an operationalisation that captures aspirations for upward social mobility, it is clear that we cannot compare the aspirations of young people from the migrant group of interest here with those from the same country of origin who have not migrated. While we contribute to research on ethnic choice effects, further research should also consider additional mechanisms, such as anticipated or experienced discrimination, that may contribute to the explanation of ethnic choice effects.https://doi.org/10.48573/dqgk-ja58; Repository: www.swissubase.ch; Ref. No. of data set: 946; TREE: https://doi.org/10.23662/FORS-DS-816-7; Repository: www.swissubase.ch; Ref. No. of data set: 816.Publicly available datasets were analyzed in this study. This data can be found at: DAB: DG performed the statistical analysis and wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.


Breastfeeding is the preferred method of infant feeding and its establishment is one of the primary goals for the infant. Allergic diseases are common in childhood, with increased morbidity. Food allergies are also associated with a strong negative impact on health-related quality of life and is a major public health problem. In addition, maternal exclusion of common allergens during pregnancy and/or lactation suggests that supplementation with regular cow’s milk formula during the first week of life should be avoided. Breast milk contains many active immune factors, such as cytokines, inflammatory mediators, signaling molecules and soluble receptors, which may also reduce the risk of allergic disease. The prophylactic effects of breastfeeding have been the subject of many studies, some with weak evidence. In this narrative review, we aim to provide an up-to-date account of the effects of prophylactic breastfeeding on food allergy and other common allergies in infants and children up to 5 years of age. Colostrum in particular has been shown to be prophylactic against food allergy. The American Academy of Pediatrics cautions that the relationship between duration of breastfeeding and incidence of food allergy in early childhood is unclear. The protective role of breastfeeding has a positive effect on allergy prevention, which is opposed by the early introduction of solid foods, but larger studies are needed to confirm the evidence. There is evidence that breastfeeding is effective in providing partial protection to infants. Food allergies are caused by repeated exposure to a food substance that triggers a specific immune response that can lead to severe health effects such anaphylactic shock. During fetal life, a large array of food antigens cross the transplacental barrier and enter the body of the fetus, with the possibility of intrauterine sensitization ,2. LaterBreastfeeding has been advocated as an solution to many a problem, from pain management in NICU infants , to negaExclusive breastfeeding is essential for at least the first 6 months of life, with continued complementary breastfeeding for the first two years of the child’s life as per WHO guidelines ,8.Breastmilk is immunologically the most relevant and essential food for the development of the newborn and the consequent maturation of immuno-defensive mechanisms ,5. It coThe intestinal microbiota system is unique, as it strengthens the intestinal barrier through bacteria colonization, protecting the neonate immune system . Due to Additionally, genetic factors control the release of anti-inflammatory and anti-allergic substances  expressed by the mammary gland . Of courThe most common form of food allergy in infants and young children under 3 years of age is sensitization to cow’s milk protein (casein or serum beta-lactoglobulin) . The mosThe time of onset for allergic symptoms varies from within the first 2 min after ingestion to the first 48 h, with expression in the gastrointestinal and/or respiratory system and/or skin; the combination of systems implies IgE sensitization , whereasThe American Academy of Breastfeeding Medicine (ABM) protocol provides a universal protocol in case of allergic symptoms . More spBreastfeeding and its beneficial effects have been of interest to the scientific community for years. The breastfeeding period is becoming one of the most critical and vulnerable periods in the life of newborns in terms of better development of the respiratory as well as other systems. Maternal nutrition plays an integral role in this phase .A literature review study investigating asthma incidence and maternal breastfeeding as a pillar of antibody transfer has concluded that milk-transmitted allergens, IC and TGF-β, may induce tolerance to asthma in offspring, while inadequate exposure to milk-transmitted allergens or offspring exposure to a specific environmental allergen may promote asthma .Breastmilk contains interleukin-7 (IL-7), which is known to be important for lymphocyte development. New studies have brought to light the fact that there is a positive correlation between the concentration of IL-7 in breastmilk and thymus development and lymphocyte production . Cohort In addition, some studies, such as the CHILD study, showed that breastfeeding is protective against asthma in the first 3 years of life . FurtherIn view of all the beneficial effects of breastfeeding, it is worthwhile to be aware of the potential effects that it may have. In particular, a number of allergic reactions can occur in infants as a result of maternal exposure to known allergens such as cow’s milk, egg, fish, gluten, peanuts and seeds . SeveralA recent systematic review found that the early introduction of eggs at 4 to 6 months of age was associated with a reduced risk of egg allergy . Two stuAdditionally, a 2019 systematic review aimed to examine the association of formula and human breastmilk with food allergy, hay fever, allergic rhinitis, atopic dermatitis, and asthma. The review found that receiving little or no breastmilk was associated with an increased risk of childhood asthma. There was a limited amount of data on food allergy, allergic rhinitis and atopic dermatitis . A similMixed-feeding infants had a higher risk of food allergy symptoms (risk ratio (RR) 1.54, 95% (CI) 1.04, 2.29) compared with 3 months breast-feeding. There was no statistically significant risk of the type of infant feeding for the diagnosis of food allergy by a physician. Prenatal maternal smoking was associated with an increase in the risk of food allergy diagnosis . In concFollowing the above studies, a new detailed study shows that late introduction of allergenic foods increases a child’s risk of developing allergies. However, there is no evidence to recommend introducing potentially allergenic foods prior to reaching six months of age . Thus, wThe gut microbiome is an established homeostasis regulator, promoting baseline immune functionality and nutrient absorption for the whole body  and an aDiets high in fat induce intestinal microbiota disorders and are a cause of intestinal inflammation .Breastfeeding and vaginal birth favourably influence the development of the infant’s gut microflora and protect against the development of allergies, as a recent study has confirmed. The intestinal microflora of breastfed infants is characterised by an early dominance of Bifidobacterium, which may have a significant impact on developing immune tolerance . In addiFrom the above data, it is clear that the increased risk of allergy in early childhood is indicative of an inadequate regulation of the immune system during this period of life . FurtherColostrum is the first food for newborns and has many important properties in the immune system. The main components of milk can be divided into three groups: bioactive factors, proteins and fats. The breastmilk of mothers of premature babies contains more protein than that of infant mothers . From eaInfants can develop allergies during the neonatal period as their immune system is regulated by T helper 2 cell (TH2) responses. As a result, the content of breastmilk is important and diverse, as it supports the child’s immune system and has factors that reduce allergies .An in-depth study conducted in 2022 investigated colostrum and breastmilk and determined the percentage of different cell types by cytometry. The results showed a difference between the total number of cells in colostrum and breastmilk and the percentage of specific stem cells. At the same time, studies have shown that CD34+ cells in colostrum and high CD133+ cells and low CD105+ cells in colostrum are associated with an increased risk of developing eczema in the first 3 months of life. To our knowledge, this is the first study of the effect of stem cells on infant diseases and leads to a better understanding of human milk . Stem ceInterestingly, these cells are multipotent, and studies in mouse models have shown that human mammary stem cells can differentiate into many tissues, including the brain, thymus, pancreas, liver, spleen, and kidney .A study on the immune response from colostrum and human milk have shown that the composition of antibodies such as Igs, LF, differ in human colostrum compared to cow’s colostrum . Human cTo reduce the incidence of allergy-related diseases in newborns in the short and long term, a controlled, prospective cohort study was conducted in Trondheim, Norway, in 2000 among pregnant women and their children . The NorIn addition, the ARCO-kids study in Korea studied the effect of breastfeeding duration in a large cohort, involving 1374 children with rhinitis aged 4–12 years, showed that long-term breast feeding (≥12 months) was associated with a reduced risk of allergic rhinitis in Korean children .Similar results were found in a Swedish study. Newborns who were breastfed for more than 4 months had a lower risk of eczema and allergic rhinitis at 4 years of age .In another study from the United States, it was shown that prolonged breastfeeding in African American patients reduced the risk of allergic rhinitis at the age of 3 years . SimilarThe beginning of the introduction of foods other than breastmilk is a very important period for the infant, in particular it is a regulator of future eating behavior and is responsible for the future development of obesity, allergies, type 2 diabetes, cardiovascular disease, and metabolic activation . The traAccording to the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), solid foods should be introduced at 4–6 months concurrently with breastfeeding, with a strong recommendation to start cow’s milk after the first year . The recPre-existing sensitization during breastfeeding is also thought to cause an allergic reaction to solid foods. For example, newborns who developed symptoms during breastfeeding due to maternal egg consumption were likely to relapse when introduced to direct feeding. Therefore, the possibility of re-sensitization (mainly to the raw and/or unbleached product) is imminent when foods that previously caused problems are gradually introduced between 4 and 11 months ,43.The European Academy of Allergy and Clinical Immunology (EAACI) guidelines mention the prevention of the production of immunoglobulin E (IgE), which is responsible for the appearance of symptoms from a possible food allergy . The mosThe evidence is clear that mothers should be encouraged to avoid certain foods during breast-feeding which may potentially be allergens in infants. Breastfeeding can be effective in the partial immunity of the offspring ,11,14. ABreastfed infants with severe symptoms  colitis complicated by stunting and/or hypoproteinemia and/or severe anemia) may be given therapeutic formula for several days to 2 weeks. Breastfeeding can be continued as normal after a follow-up visit to a specialist physician, so that appropriate counselling can be given to the mother ,14.Introducing gluten to the mother’s diet during breastfeeding may reduce the risk of not only celiac disease, but also type 1 diabetes and wheat allergy, according to a 2017 systematic review . Next, iStudies that have evaluated the consumption of peanuts during lactation have shown a wide range of results from reduced to increased sensitization ,48,49,50The efficacy Is defined by the patient’s tolerance to the increase in amount over time, so that the tolerated amount could later be consumed in the basic diet . Of courWhile it has been shown that maternal dietary intake during pregnancy and breastfeeding can, to some extent, influence immune markers in the child that may alter the risk of allergy development, the multiple variables of food antigens differ from person to person, so we must be careful to interpret these complex relationships clearly. Hence, the EAACI guidelines  recommenThe majority of trials did not find a reduction in the prevalence of food allergy when women avoided food allergens during pregnancy and postpartum. Food allergens are not isolated, so avoiding a food group in a population at risk outweighs the benefits, as reducing nutrient and fiber intake negatively affects the health of women and infants.Breastfeeding is the most important protective nutrient for infant development and contributes to the maturation of defense mechanisms in their adult future lives. The preventive role of breastfeeding has a positive effect on allergy prevention, which is countered by the early introduction of solid foods, but large studies are needed to consolidate the evidence. Breastfeeding is effective in providing partial protection to infants.In conclusion, all mothers, regardless of allergy risk, should be encouraged to avoid certain foods that can cause allergies in their infants while breastfeeding. Proper and balanced nutrition prior and during lactation will help improve breastmilk quality and help in addressing allergies more effectively or even negate them.


This study identified the current state of knowledge about the Quality of Life (QoL) of siblings of children who are deaf and hard of hearing (DHH), have a vision impairment (VI) or motor impairment (MI). Additionally, factors associated with individual variation in QoL were examined. A scoping review was performed using PsycInfo, ERIC, Web of Science, and CINAHL. Empirical studies with siblings (age 0-18 years) of children who are DHH, have a VI or MI that investigate the QoL of siblings were included. A total of 1746 studies were identified of which 11 met the inclusion criteria. The results showed that QoL has different interpretations and various measurement tools are used. The findings showed both positive and negative outcomes for the QoL of siblings. For example, family cohesion was found as a positive consequence. A negative consequence could be a higher score on problem behavior. Personal and parental characteristics such as age and parental availability were two main factors related to individual variation in QoL. Insight in the factors related to individual variation may help researchers to consider the research perspective. In addition, healthcare providers can use the information to be either aware or intervene on specific factors that are related to the QoL of the children who are DHH, have a VI or MI and their siblings. Living with a child with a disability affects all family members. For example, previous research showed that mothers show high levels of stress  and low QoL is widely used in support of people with intellectual disabilities , which gThe current study has a specific focus on childhood siblings (age 0–18 years) of children who are deaf or hard of hearing (DHH), have a vision impairment (VI) or motor impairment (MI). These groups have in common that they have a sibling with a physical disability, either sensory or motor, which puts a strain on interaction and communication because of technical reasons but not so much because of a lack of cognition as in children with intellectual disabilities. A further reason to combine these three groups is that the prevalence of these disabilities is low .Because of the issues and challenges that siblings of children with motor and sensor impairments have in common, it is logical to study them together. This has the additional benefit that we preserve ourselves from the diagnostic overshadowing bias . In diagSiblings of children who are DHH, have a VI or MI can share experiences with each other and with siblings of children with chronic diseases or (neuro)developmental disorders, but other situations can be dissimilar . AlthougPerceptions of children with disabilities have changed and now incorporate the social context , 37 and The present paper examines the current state of knowledge on the QoL of siblings of children who are DHH, have a VI or MI and the factors related to individual variation. A scoping review was conducted to identify knowledge gaps and clarify key concepts . A scopiThe review was set up according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist . To idenStudies were only included when they were published in English-language, peer-reviewed journals between 2002 and 2021 and studied siblings (age 0–18 years) of children who are DHH, have a VI or MI. Both qualitative and quantitative studies were included if they focused on the QoL of the siblings. We followed the conceptualization of Schalock et al. , as descTo answer the research questions, the first and second authors extracted the data from each included study using a data extraction list see . For datn = 16). In three studies, the outcomes were not related to the QoL of siblings, or the study was not empirical (n = 6). The manuscripts of 20 studies were not peer-reviewed, and 10 studies were not written in English. Eventually, nine studies were included for data extraction. Additional studies were searched by checking the list of references of the nine selected articles. Based on the title, 17 studies were found eligible for inclusion. These 17 studies were checked by the first and second authors in the same way as described earlier. We therefore included two of these articles that met all the inclusion criteria and yielded a final sample of 11 studies. See the flowchart in A flowchart of the selection process is depicted in All studies were published between 2003 and 2021. The study characteristics are described in The type of impairment varied across the included studies. The studies are categorized by DHH, VIs, MIs, and mixed disabilities. With this last category, we meant all the studies that did not focus on one type of disability but had a sample of siblings of children with different types of disabilities. In The first research question was about what is known about the QoL of siblings of children who are DHH, have a VI or MI. Subsequently, outcomes, assessment tools, control groups, and positive and negative consequences for the QoL of the siblings are described. See The outcomes of the included studies varied widely. For clarity, we clustered studies with corresponding outcome measures, resulting in six themes, namely, QoL , wellbeing, relationships, adjustment, mature behavior, and self-perception. These themes were composed by the first and second authors, based on the results of the included studies, and found their basis in the factors and domains within the QoL framework as described by Schalock et al. .QoL : Two studies reported results specifically about the overall QoL. No statistical differences for QoL were found between siblings of children with mixed impairments and control groups (#9), which means that there were no differences in the subscales behavior, self-esteem, and mental health. Siblings of children with VI had a higher health-related QoL compared to the child with VI (#8).Wellbeing: The results concerning the wellbeing of siblings were mixed. No statistical differences were found between siblings of children who are DHH and controls on emotional wellbeing (#4), which indicated that the psychosocial adjustment, social competence, and self-worth of the siblings are within the normal range for their age. In contrast, siblings of children with mixed impairments reported both negative emotions, such as worries in a semi-structured interview. In addition, one study even reported a significantly higher score on depression for siblings of children with mixed impairments compared to controls (#9) and positive emotions, such as more appreciation for life (#11).Relationships: Several studies found positive findings for relationships. Namely, siblings of children with mixed impairments had a significantly higher score on family cohesion than that of the controls (#9). In addition, in interviews, siblings had positive comments about the relationship with the child with the impairment , for example, about the close relationship between siblings. Nonetheless, one study, which involved families of children with VI, found an overall negative impact on family interaction (#8). In interviews, more than half of the siblings of children with mixed impairments gave negative comments about parental attention (#6), for example, that parents spend more time with the child with the impairment compared to the sibling without a disability.Adjustment: Adjustment of siblings was reported in several studies. Siblings were found to have fewer problems in psychological adjustment compared to norm groups. More specifically they showed better adjustment on the subscales “total difficulties” and “hyperactivity” of the Strengths and Difficulties Questionnaire (SDQ) (#2). With regard to prosocial behavior, siblings showed more prosocial behavior compared to their siblings with VI (#7) and peers without a brother or sister with disabilities (#10). Furthermore, they were more likely to score in the abnormal range of the SDQ, meaning they showed high levels of prosocial behavior (#2). However, siblings showed also higher scores on internalizing behavior compared to those of control participants and higher scores on externalizing behavior compared to those of their siblings with MI (#3). However, no statistical differences were found for difficulties compared to their sibling with VI (#7).Mature behavior: One study reported that siblings of children who are DHH had worries about the future (#4). Siblings of children who are DHH or have mixed impairments indicated in an interview to have feelings of responsibility for their sibling with a disability . However, no statistical differences for responsibility were found compared to siblings of children who are DHH (#5).Self-perception: The one study that investigated self-perception found that scores on self-perception were rather high for siblings of children who are DHH, but they were not significantly different from the mean standard scores of the Greek population (#4).Since the outcomes of the included studies varied largely, possible variation as a result of differences in assessment tools was examined. A total of 21 different assessment tools were used in the 11 studies see also . Only twhree studies did not use control groups , whereas the remaining studies used three kinds of control groups, namely, the norm groups from the assessment tool , a control group consisting of siblings with the impairment , and a control group of children who did not have a brother or sister with a disability . The latter seems to be the more appropriate control group, although the controls in those four studies were matched on only age range, not age and sex. Studies # 3, 5, 9, and 10 compared siblings of children with a disability with a control group consisting of siblings of children without a disability. It appeared that siblings of children with mixed disabilities had a significantly higher score on depression than the controls (#9). QoL was mostly equal for both groups, and only siblings of children with mixed disabilities had a significantly higher score on family cohesion. Study #3 found that siblings of children with MI scored significantly higher on internalizing behavior than the controls. Study #5 found no significant differences between the siblings and controls. In contrast, study #10 found a significantly higher overall score for prosocial tendencies for the siblings.Studies #3, 7, and 8 compared siblings with a child with a disability. Siblings of children with VI showed significantly more prosocial behavior (#7) and had significantly higher scores on QoL (#8) than the children with VI. In contrast, siblings of children with MI showed significantly more externalizing behavior compared to their brother or sister with MI (#3).Study #2 compared the psychosocial functioning of siblings with the norms of the assessment tool. It appeared that siblings of children with MI had significantly fewer problems related to psychological adjustment compared to norms for British children. The scores on self-perception of siblings of children who are DHH were not significantly different from the standard mean scores (#4).The review showed that both positive and negative consequences were found for siblings. To start with the negative consequences, two studies reported siblings having more behavior problems than controls. Specifically, siblings had significantly more internalizing behavior problems than the controls and showed significantly more externalizing behaviors than the child with MI (#3). A negative correlation was found between the severity of hearing loss and behavioral problems in siblings (#5), which meant that the more severe the hearing loss the fewer behavioral problems were found in the siblings. The same study also showed that when siblings perceived their relationship with the child who is DHH to be negative, more interpersonal problems appeared (#5). Siblings of a child with a disability had a significantly higher score on depression than siblings of children without a disability (#9). Further, siblings had worries about the child with a disability and took upon themselves many responsibilities, such as helping parents with household work or taking care of their siblings . The older siblings were, the more they reported feelings of embarrassment (#4). Lastly, study #8 reported an impaired QoL for all family members. Overall, there was an adverse impact of the impairment on the family and family functioning. With regard to parental attention, siblings indicated that they received less parental attention compared to their siblings with a disability (#6).At the same time, some of the reviewed studies also found several neutral and positive consequences with regard to the QoL of the siblings. The self-perception scores of siblings were not significantly different from standard mean scores (#4). The family interaction was perceived as positive , and no significant differences were found for emotional and behavioral adjustment, self-perception, parental attention, household responsibilities (#5), and QoL (#9). Actually, in contrast to study #8, the family scores of the latter domain were significantly higher for siblings (#9). Two studies found that siblings experienced a good relationship with their sibling with a disability . In addition, siblings showed more prosocial behavior  and better psychological adjustment compared to British norms (#2). Whether this also applies to health-related QoL is unclear, but compared to their sibling with a disability, they scored higher on health-related QoL (#8).Next to the positive consequences for QoL, some studies also found positive associations between different domains of QoL. The attitudes of siblings toward illness, satisfaction with the family, sibling warmth and conflict, and classmate and close friend support were strongly, positively, and significantly associated with self-concept (#1). Specifically, satisfaction with the family was significantly associated with all dimensions of sibling adjustment (#1). In study #4, adjustment  was also significantly and positively associated with self-perception and global self-esteem. Siblings who perceived positive relationships with their sibling with a disability also expressed more warmth and closeness (#5).The factors that are associated with individual variation in QoL of siblings of children with a disability as described in the 11 studies are listed below. From the included studies, empirical evidence for individual variation was not found for many variables. However, all studies named potential variables responsible for individual variation when discussing the results. Factors for individual variation are therefore divided into examined factors and potential factors.The type of impairment in relation to the outcomes on QoL of the siblings was studied. Disabilities were categorized into: DHH, VI, and MI. Studies #9, 10, and 11 were not included in this analysis because of the large heterogeneity in disabilities of the siblings of the participants. Overall, we found no general trend when analyzing the results based on the type of impairment. The complications in studying this question were the large variety of themes under study, different types of assessment tools, and the small number of studies that had comparable populations as the participants.Impairment characteristics might be relevant for individual variation. The included studies suggested in their discussion that treatment and prognosis of the impairment can relate to individual variation in the QoL of siblings (#8) and that onset and consequences of the impairment (#1) and progressiveness (#3) may negatively impact the QoL of siblings. The impact of the severity of the impairment differed by disability group and the domain of functioning. In study #5, a significant negative association was found between the severity of hearing loss and behavioral problems of the sibling. But for siblings of children with VI in study #8, the opposite association was found for family functioning; families with a child with a severe VI reported worse family functioning. In study #1, no significant association between the severity of the MI and the QoL of siblings was found. In study #4, the possibility of communicating orally by children who are DHH had a positive impact on QoL. In addition, in study #6, siblings indicated that they felt less impacted when their sibling who is DHH had good speech intelligibility.The age of both the child with the disability and the sibling is associated with variation in parenting and psychosocial wellbeing. The parents indicated that older siblings of children with hearing impairments showed fewer interpersonal concerns and less fear and conflict (#5) than younger siblings. Studies #4 and 5 suggested in their discussion that not so much birth order but rather the length of time between births of siblings can create individual variation. Small differences in age between the child with the impairment and the sibling were proposed to lead to more negative feelings (#4) in comparison to larger age differences. In study #10, a difference was found in aspects of prosocial tendencies between older and younger siblings; younger siblings showed more public and altruistic prosocial tendencies than older siblings, but less prosocial tendencies in anonymous and compliant situations.The effect of the sex of the siblings was examined in four studies. Whereas study #4 found no significant differences by sex, studies #1, 5, and 10 did. Brothers showed more externalizing behavior (#5) and a significantly higher self-concept (#1) than those of sisters, while sisters showed more prosocial behavior  and nurturing and dominance in sibling relationships (#5). In study #10, brothers showed more public prosocial behaviors than those of sisters, and the latter showed more emotional and altruistic prosocial behaviors.According to study #5, a difficult temperament in siblings is significantly related to more externalizing and internalizing behavior. In addition, study #5 argued that a more positive temperament of siblings may help them to adapt to the situation of having a brother or sister with a disability resulting in fewer behavior problems. However, if siblings have high amounts of domestic responsibility, it may negatively impact the QoL of the sibling (#3). It was suggested that knowledge of the impairment of their sibling also may be helpful .Parental and family characteristics can relate to the relationship between the child with the disability and the QoL of the sibling. Two studies took these factors into account. In study #4, siblings from bigger families reported significantly more negative feelings than siblings from smaller families. Studies #4 and 9 found that a permanent job for at least one of the parents was a protective factor for the QoL of the sibling. The discussion section of several studies implied that parental and family characteristics could be potential factors. Study #5 suggested that the stress of parents may negatively impact the QoL of siblings. In contrast, good communication between parent and child , parental availability , and a healthy family environment  were suggested as positive factors for the wellbeing of siblings of children with disabilities. The culture and ethnicity of the family may also play a role in the QoL of the sibling (#5), although the specific impact was not clearly described. According to studies #6 and 10, parenting behavior may also facilitate the prosocial behavior of the siblings. Study #4 suggested that whether a child who is DHH goes to a regular school or a residential school may also have an impact on sibling relationships. The rationale is that a primarily hearing environment creates more opportunities for interaction than a residential school, which in turn stimulates sibling relationships at home.QoL of siblings can differ based on who completed the report. For example, study #2 found that mothers regularly reported more problems than fathers, and study #8 found that children reported significantly fewer problems for themselves than their parents. A possible explanation for systematic differences in response is given in study #5, which mentions that parental reports can be affected by the (negative) feelings of the parents.Study #1 found that classmate support was significantly and positively related to the self-concept of the siblings and the authors suggested a protective role of peer relations in sibling adjustment outcomes. Study #11 mentioned the importance of peers and participation in support groups for creating positive feelings for the sibling.This scoping review examined the QoL of siblings of children who are DHH, have a VI or MI. The current review should complement previous reviews that focused on siblings with other conditions, such as chronic illnesses, intellectual disabilities, or neurodevelopmental disorders, which are not comparable to siblings of children with motor or sensory disabilities.The first research question addressed the current state of knowledge on the QoL of siblings of children who are DHH, have a VI or MI. The included studies assessed varying developmental domains for which they used a variety of terms and operationalizations of QoL. For example, Bellin et al.  investigDespite the abovementioned methodological issues, some conclusions can be drawn regarding the first research question. For clarity, the findings of the studies were categorized into themes by the first and second authors: QoL , wellbeing, relationships, adjustment, mature behavior, and self-perception. These themes correspond with three of the eight domains of Schalock et al. , that isFor the first research question, we further investigated which assessment tools were used, which control group was used, and what the positive and negative consequences were for the siblings. A large variety of assessment tools were used. If the same assessment tool was used in different studies, the results seemed consistent between the studies. For the SPQ, CBCL, and SDQ, matching results were found. The use of the SDQ in three studies showed that siblings acted more prosocially than controls , 50, andOther researchers also found positive and negative consequences for the QoL of siblings in the current review on similar topics with other groups , 56, 57.The second research question concerned the factors that could be associated with individual variation in QoL of siblings of children who are DHH, have a VI or MI. While studies identified several factors affecting the QoL of siblings, these have not yet been studied thoroughly. Amongst the better-studied factors are age and sex. Older siblings showed less interpersonal concerns, fear, and conflict than younger siblings . An explNext to factors within the individual, external factors impact the QoL of siblings, such as good communication within the family and parental availability , 49, 54.The conceptualization of QoL as done by Schalock et al.  does notSome limitations of this review must be considered. First, while it was known that this specific topic is relatively little researched, we restricted potential findings to peer-reviewed English scientific articles. As a result, no gray literature, for example, internal reports, were included in the review. In addition, only articles published in the last 20 years were considered, potentially excluding older but relevant studies. This choice was, however, deliberately made because more recent societal developments formed a contraindication to include older publications. Examples of such developments are as follows: improvements in technology and neonatal care; changes in rehabilitation practices by initiatives such as the Convention on the Rights of Persons with Disabilities (CRPD) and the International Classification of Functioning, Disability, and Health for Children and Youth (ICF-CY) , 38; andSecond, the operationalization of QoL is tenuous. Roberts  stated tFinally, although not a limitation in the sense that the inclusion criteria were too strict, the included studies were only conducted in Europe and the United States of America. This may give a one-sided perspective, as parenting and family relations differ across countries and cultures. For example, in Asian and African countries, it is more typical to live in communities and strive for group instead of individual wellbeing compared to Western countries. As a result, demands on children and the affection shown to them differ as well .In the current scoping review, we found that many studies suggested that parenting-related variables may impact the QoL of siblings. For instance, parental availability and good communication between the family members were often suggested , 49, 54.The implication of focusing on parenting-relating variables fits perfectly with current trends in rehabilitation to focus on family-centered care . The infSiblings often act as young carers , 63. CarWithin interventions, a distinction is made between modifiable and non-modifiable factors . For exaTo our surprise variables such as socioeconomic status, caregiver education and access to resources were not mentioned to account for individual variation in QoL of siblings. Given their universal importance for early intervention , we woulFuture research on the QoL of siblings should consider whose information is used. Half of the studies analyzed the QoL of siblings with information from parents, not of the siblings themselves, which carries the risk of a one-sided focus . The emoThe present scoping review provides an overview of the current knowledge on the QoL of siblings of children who are DHH, have a VI or MI, based on research from 2003 to 2021. Limited research specifically focused on the QoL of siblings of children who are DHH, have a VI or MI. The review included 11 studies that examined the QoL of siblings, using tools such as the SDQ and CBCL. Negative consequences observed in the QoL of the siblings include higher scores on depression  and inte