Background: Healthy and sustainable food systems underpin the well-being of Indigenous peoples. Increasingly governments are taking action to improve diets via population-wide policies. The United Nations Declaration on the Rights of Indigenous People states that Indigenous peoples have the right to participate in all decisions that affect them. We analysed Australian national food and nutrition policy processes to determine: (i) the participation of Aboriginal organisations, (ii) the issues raised in Aboriginal organisations’ policy submissions, and (iii) the extent to which Aboriginal organisations’ recommendations were addressed in final policy documents.Methods: Political economy and cultural safety lenses informed the study design. We analysed publicly-available documents for Australian population-wide food and nutrition policy consultations occurring 2008-2018. Data sources were policy documents, committee reports, terms of reference and consultation submissions. The submissions made by Aboriginal organisations were thematically analysed and key policy recommendations extracted. We examined the extent to which key recommendations made by Aboriginal organisations were included in the subsequent policy documents.Results: Five food and nutrition policy processes received submissions from Aboriginal organisations. Key themes centred on self-determination, culturally-appropriate approaches to health, and the need to address food insecurity and social determinants of health. These messages were underrepresented in final policy documents, and Aboriginal people were not included in any committees overseeing policy development processes.Conclusion: This analysis suggests that very few Aboriginal organisations have participated in Australian population-wide food and nutrition policy processes and that these policy development processes are culturally unsafe. In order to operationalise First Nations peoples’ right to self-determination, alternative mechanisms are required to redress the power imbalances preventing the full participation of Aboriginal and Torres Strait Islander peoples in population-wide food and nutrition policy decisions. This means reflecting on deeply embedded institutional structures and the normative assumptions upon which they rest. For many First Nations peoples food is more than a source of energy and nutrients; it is inculcated in cultural identity, land, family and history, as well as physical, social, emotional and spiritual well-being. European colonisation severely disrupted and marginalised the cultural practices and food systems of First Nations peoples around the world, manifesting in the social, economic and health inequities that persist today. Nevertheless, First Nations peoples have survived and continue to hold cultural, environmental and food system knowledge, which is a valuable resource, not only for the health of First Nations peoples, but also for the sustainable development of the broader industrialised world. Before colonisation, First Nations peoples worldwide were the custodians of sustainable food systems which maintained human health and protected biodiverse ecosystems for millennia. In this paper we respectfully use the term ‘Aboriginal’ to describe First Nations peoples of Australia, acknowledging that these comprise many different nations, language groups, geographic areas, cultural and kinship systems. Aboriginal people have developed healthy and sustainable food systems based on transgenerational knowledge of seasonal food sources and preparation methods. Aboriginal people hunted and gathered, practiced agriculture and aquaculture, and made sophisticated technological innovations to procure and process food. As a result the precolonial diets of Aboriginal people were derived from a wide variety of plant and animal foods, high in protein, fibre and micronutrients and low in fat, sugar, and salt.Aboriginal and Torres Strait Islander peoples are the traditional owners of Australia with a history of over 65000 years, representing the world’s longest surviving continuous culture. This changed with European invasion and colonisation of Australia because Aboriginal people were dispossessed from their homelands and denied access to their cultural knowledge and food systems. Introduced species and Western agricultural practices caused environmental degradation further reducing availability of traditional food sources. Traditional, nutrient-dense diets were first replaced by government-controlled rations of flour, rice, sugar, tea and, occasionally, poor-quality meat; then by imposed colonial-style cooking during the policy of assimilation, which aimed to extinguish all traces of Aboriginal cultures. The presence of malnutrition was often used to justify the forced removal of Aboriginal children from their families, further disrupting the passage of traditional food knowledge through the generations. Thus, changes to food and nutrition were both an instrument and an outcome of colonisation.Precolonial Aboriginal society was healthy, self-determined and free from diet-related chronic disease. Like other First Peoples, Aboriginal Australians have undergone a nutrition transition characterised by a rapid Westernisation of dietary patterns and sharp increase in prevalence of obesity and chronic disease. Dietary factors and high body mass are each responsible for approximately 15% of the gap in health outcomes between Aboriginal and non-Aboriginal Australians. Furthermore, more than 1 in 5 (22%) Aboriginal people experience food insecurity, with the prevalence even higher (31%) in remote Australia. The social determinants of health, including education, employment, income and housing, all contribute to the food and nutrition inequity experienced by Aboriginal people. These determinants are underscored and amplified by the historical and ongoing processes of colonisation, dispossession and disempowerment as well as interpersonal and institutional racism.Colonisation and industrialisation of traditional food systems have dramatically changed the diets of First Nations peoples internationally. Moreover, the absence of a treaty or constitutional arrangements guaranteeing Aboriginal people a political ‘voice’ to public institutions sets Australia apart from similar Western colonised nations when it comes to the rights of First Nations peoples. The United Nations (Article 18) has affirmed that:The factors underpinning Aboriginal food and nutrition are ultimately political. First Nations academics argue that cultural imperialism, institutional failure and unequal distribution of power and opportunities for political participation have produced policies which contribute to health inequity for Aboriginal people.“Indigenous peoples have the right to participate in decision-making in matters which would affect their rights, through representatives chosen by themselves in accordance with their own procedures.” Below, we provide a brief overview of the political context of Aboriginal affairs and food and nutrition policy-making. We then introduce our intersectional approach to policy analysis combining two theoretical perspectives which we apply in this examination of food and nutrition policy-making in Australia.In this article, we examine the extent to which Aboriginal people, through their representative organisations, have had a voice in developing population-wide policies related to healthy and sustainable food systems in Australia. In the Australian context, Aboriginal community-controlled organisations, which are governed by and accountable to their local Aboriginal communities, frequently represent Aboriginal peoples in policy debates regarding matters that affect them. This occurred during a time of civil rights activism, which also saw the establishment of the first Aboriginal community-controlled organisations, which were “an important institutional manifestation of the politics of self-determination.” From the 1970s, self-determination was part of the Government policy approach to Aboriginal affairs, with Federal funding provided to Aboriginal organisations and the establishment, in 1990, of a national representative and administrative body, the Aboriginal and Torres Strait Islander Commission (ATSIC). The conservative opposition party voted against the creation of ATSIC and when they came to power, in 1996, had a fractious relationship with Aboriginal leaders. The abolition of ATSIC, in 2004, marked the end of the era of self-determination in Aboriginal affairs policy.The Commonwealth of Australia is a federation comprising 6 states and 2 territories, established in 1901. The Federal Government has only had the power to develop policy for Aboriginal people since 1967, following a landmark referendum which enabled Aboriginal people to be officially counted in the Australian population. However, there has only been one dedicated national food and nutrition policy, the National Aboriginal and Torres Strait Islander Nutrition Strategy and Action Plan 2000-2010 (NATSINSAP). NATSINSAP was developed, following broad Aboriginal community consultation and oversight, as a component of Eat Well Australia, Australia’s population-wide food and nutrition strategy. Since NATSINSAP and Eat Well Australia expired in 2010, there has been no comprehensive national nutrition policy for either the general Australian population or for Aboriginal peoples.There has been a long history of Aboriginal involvement in food and nutrition policy. For example, when ATSIC was in operation, one of its responsibilities was the Community Housing and Infrastructure Program, which included guidelines and standards for housing design to enable, amongst other things, adequate food storage and preparation. Australia, along with New Zealand, Canada and the United States, initially voted against the declaration; however, eventually supported it following the election of a new Labor  Federal Government. A watershed moment in Australian politics occurred in February 2008, when the Prime Minister delivered a Parliamentary apology to the Aboriginal people, known as the  Stolen Generations, who, as children, were forcibly removed from their families by previous Governments under the policy of assimilation. The same year, following an Aboriginal-led, rights-based advocacy campaign, the Prime Minister and Opposition leader made a bipartisan commitment to “close the gaps” in health status and life expectancy between Aboriginal and non-Aboriginal Australians, with the full participation of Aboriginal people and their representative bodies.In 2007, the United Nations adopted the Declaration on the Rights of Indigenous Peoples, which included the right to self-determination.Closing the Gap policy framework has been criticised for being based on a deficits discourse, which defines success as achieving statistical parity with the non-Aboriginal ‘norm,’ rather than outcomes defined by Aboriginal people. This is likely because it was developed by the Council of Australian Governments without substantive formal Aboriginal participation in the policy process. Furthermore, with the exception of a strategy for remote food stores, food and nutrition were almost completely absent from the Closing the Gap policy agenda. By contrast, the 2013 National Aboriginal and Torres Strait Islander Health Plan was generally welcomed by Aboriginal leaders as it was developed following extensive engagement with Aboriginal organisations and communities via written submissions and consultation forums. It emphasised the cultural strengths of Aboriginal people as central to health policy and the need to address racism. The Health Plan also included significant food security and nutrition elements; however, the Federal Labor Government lost the election soon after the Health Plan was launched and, as a result, it remains largely unimplemented. Nonetheless, Aboriginal and Torres Strait Islander communities and organisations have continued to advocate for its implementation and for more meaningful engagement in the policy process. In 2019, the partnership agreement between the Council of Australian Governments and a coalition of Aboriginal community-controlled peak organisations recalibrated the nature of policy development to ensure that policies directly affecting Aboriginal people are based on shared decision-making and consider cultural safety and self-determination. This culminated, in 2020, in the publication of a revised set of Closing the Gap targets which, for the first time, were developed in partnership with Aboriginal peak organisations.Over 10 years have passed since these commitments were made and the health gap persists. The  The prominence of food and nutrition on the Federal Government’s Aboriginal health policy agenda has varied over time for a number of reasons. Furthermore, 80% of Government funding for Aboriginal people is spent through universal, population-wide programs and services. It is these population-wide policy processes that are the focus of the current analysis. Food and nutrition policy development in Australia involves a varying degree of public consultation. Inviting written submissions is a common strategy used to engage stakeholders in the policy process. Following a public consultation, stakeholder submissions are usually published on publicly-available Government websites.Promoting healthy and sustainable food systems and improving population nutrition requires a comprehensive, multisector policy response. From an equity perspective, targeted food and nutrition strategies should be complemented by population-wide policies, both of which must meet the needs of the Aboriginal population as determined by them. To operationalise this idea, we combined political economy and cultural safety perspectives to examine Aboriginal organisations’ participation in population-level food and nutrition policy-making processes.The multiple and intersecting concerns related to policy development and Aboriginal peoples require appropriate methodologies. As a team comprising both Aboriginal and non-Aboriginal researchers we drew on Durie’s concept of ‘research at the interface’ between Indigenous and non-Indigenous knowledge systems. However, political economy theories have been underutilised in the context of Aboriginal food and nutrition. The international food and data sovereignty movements highlight the political, economic and cultural nature of First Nations peoples’ aspirations for food system transformation, and the need for appropriate evaluation indicators and data governance. Political economy analysis is concerned with the interaction of political and economic processes and the distribution of power and resources between different groups in society. This includes examination of the roles of institutions, incentives, ideas, interest groups and power relations in influencing policy development.There are calls for nutrition advocates and policy-makers to apply political economy analyses to improve policy-making for healthy and sustainable food systems. In theory, an individual actor or interest group has the freedom to contribute ideas in policy debates, however their power to influence decisions is shaped by the historical, social, cultural, political and economic properties of society. Policy-making has embedded and invisible institutional structures, rules and resources that are drawn-on throughout the policy process, which may either enable or constrain the participation of certain groups. In order to harness these constructs, our analysis was informed by Hall’s political economy framework, which posits that policy processes are determined by actors’ interests and ideas and mediated through institutions.Key to this approach are questions of signification (who makes the rules?), domination , legitimation (what is legitimate knowledge?) and interpretation (how we understand and frame the world?) Additionally, there has been a cultural policy reform agenda in Australia, emphasising the cultural strengths of Aboriginal peoples as central to all health policy. When developing food and nutrition policy in Australia it is, therefore, essential to recognise the influences of historical trauma and ongoing colonisation, dominant culture, white privilege and power, and both overt and institutional racism, which serve to devalue the cultural strengths of Aboriginal people.Political economy frameworks do not explicitly account for cultural identity. We refer above to the cultural destruction of Aboriginal food systems and the enduring impacts of the policies imposed, without consultation, on Aboriginal Australians by the colonial governments. The food sovereignty movement seeks to reframe relationships between Western governments and First Nations Peoples through, for example, consideration of cultural identity and participation in policy-making processe. – has increased in prominence in Australian health policy as a lens for analysing the power relations between health personnel and the people they serve. Cultural safety is concerned with ‘reflexivity, dialogue, reducing power differences, decolonization and regardful care,’ concepts that challenge the institutional norms of public health policy-making. A key challenge for policy-makers is to reflect on how the policy-making process can – unintentionally – embed institutional racism, especially with legislation that renders Aboriginal people ‘legally invisible.’ These challenges are further amplified in universal, population-wide policy processes where Aboriginal people are not a key focus. Therefore, aligning political economy  and cultural safety  theories provides for a unique methodological analysis at the cultural interface.The concept of “cultural safety” – championed by Māori nurse Irihapeti Ramsdeni) the participation of Aboriginal organisations in these policy processes; (ii) the common issues in the submissions made by Aboriginal organisations; and (iii) the extent to which key issues raised in Aboriginal organisations’ submissions were addressed in final policy documents.This study applied political economy and cultural safety lenses to understand how Aboriginal issues have been included and represented in national population-wide food and nutrition policy processes that took place in Australia between 2008 and 2018. We were specifically interested in: . Mandate Aboriginal peoples’ membership on all food and nutrition policy development committees. Implement the recommendations made within the Uluru Statement from the Heart, including a constitutionally enshrined Aboriginal voice to Parliament. Ensure adequate and sustainable funding to Aboriginal organisations, that is not burdened by excessive administrative and accreditation requirements, to increase capacity to participate in policy processes. Cultural safety needs to be embedded in the institutional design of policy participation processes.  Self-determination is a right of Indigenous Peoples that needs to be embedded in food and nutrition policy, strategy and action. Our findings indicate existing national-level, population-wide food and nutrition policy consultation processes systematically disadvantage Aboriginal and Torres Strait Islander Australians. With regard to population-wide food and nutrition policy, Australia is not meeting its obligations under the United National Declaration on the Rights of Indigenous Peoples. Our analysis of food and nutrition policy-making in Australia spanned the years 2008-2018. The year 2008 was selected as a starting point for this analysis as it marked the commencement of a new Federal Labor Government in Australia, who brought a renewed policy focus on both Aboriginal health and preventative health . This period coincides with growing momentum for asserting First Peoples’ rights to equitable health and self-determination both internationally and in Australia. Importantly, this timeframe covers the 10-year period following the United Nations Declaration on the Rights of Indigenous Peoples and the commitment by Australian governments to close the life expectancy gap between its First Peoples and non-Indigenous Australians; therefore, this analysis will interrogate the extent to which the Australian government has met these commitments with respect to population-wide food and nutrition policy. This timeline selection also aligns with recommendations that timeframes of at least 10 years are required to adequately study policy processes. Although both Commonwealth  and state/territory governments have responsibilities in food and nutrition policy and Aboriginal affairs in Australia, our analysis focussed on population-wide food and nutrition policy-making at the national level only.A qualitative policy document analysis was used to examine the inclusion of Aboriginal organisations’ issues in Australian food and nutrition policy processes. Policy analysis is a field of research which can enable understanding of how and why policy proposals are enacted (or rejected) and the values, ideas, interests and institutional contexts underpinning government decisions.i) policy documents, (ii) committee reports and committee terms of reference, and (iii) stakeholder submissions concerning food and nutrition policy, all of which are considered to be relevant to policy development processes. Documents were collected from publicly available government websites. Relevant policies were initially identified by reviewing the Scoping study to inform development of a National Nutrition Policy for Australia, which provides a detailed timeline of food and nutrition policy developments until 2013. Additional policy processes were identified through searching the Commonwealth Department of Health consultations page  and the Parliament of Australia committees and inquiries page (https://www.aph.gov.au/Parliamentary_Business/Committees) using the search terms “food,” “nutrition,” “preventative health” and “obesity.” To be included in the initial analysis, policy development processes had to meet the following criteria:Data sources were national  Included public consultation with stakeholder submissions published online. Policies which specifically targeted the Aboriginal and/or Torres Strait Islander population were excluded as were policies that were only relevant to a particular State or Territory context. For the purpose of this analysis an Aboriginal organisation was defined as being controlled and operated by Aboriginal and/or Torres Strait Islander people and/or governed by an Aboriginal Board and formed to pursue agreed objectives that align with Aboriginal values and beliefs. Data analysis was guided by political economy and cultural safety lenses. According to the 3 key objectives for this study, data were analysed in 3 distinct stages. Documents were arranged into a policy timeline to convey institutional time and trajectory. A data extraction template was developed in Microsoft Excel . The following details were extracted from the corresponding website and supporting documents of each policy episode (where relevant): governance over policy process , year policy process commenced, year final policy document was published, policy goal, objectives/terms of reference, consultation process, relevant consultation documents, total number of consultation submissions received, number of consultation submissions received from organisations , number of submissions from Aboriginal organisations and other processes (if any) employed to consult with Aboriginal stakeholders. Committee terms of reference were searched for key words  and committee members overseeing the policy development processes were examined for Aboriginal membership by searching the members’ online profiles to detect whether committee members identified as Aboriginal or Torres Strait Islander or represented Aboriginal organisations. The presence or absence of Aboriginal organisations’ submissions to each policy process was identified as well as the proportion of total organisational submissions made by Aboriginal organisations. All policy processes that included at least one publicly-available written submission from an Aboriginal organisation proceeded to the next stage of analysis. and content analysis was used to examine Aboriginal organisations’ perspectives regarding population-wide national food and nutrition policy within relevant consultation submissions. A second data extraction template was developed to record summary details for each policy consultation processes in which at least 1 Aboriginal organisation participated. The following details were extracted from each submission made by an Aboriginal organisation: the type of organisation, the sector represented, jurisdiction, prominent issues and recommendations.In stage 2, a combination of thematic analysis During a second appraisal of the data, key food and nutrition issues, policy recommendations, concerns about food/nutrition policy actions and other concerns about the policy process were identified. As each idea or recommendation was observed, a code was applied. For example, a ‘food security’ code was applied to a stakeholder recommendation for ‘improved access to fresh food.’ Codes were developed iteratively as each new submission was analysed then, as patterns were identified, codes were grouped into categories, from which higher-order themes were created. Once themes were derived, content analysis was applied across all submissions to determine which issues and recommendations were most frequently raised by Aboriginal organisations.To synthesise Aboriginal organisations’ priorities across the range of consultation submissions for all national food and nutrition policy processes, the most prominent issues and recommendations were identified using thematic analysis. Thematic analysis involves applying codes, sorting and organising data into related themes. Submissions were uploaded into NVivo analysis software  and grouped based on the associated policy process. Consistent with recommended procedures for thematic analysis, the entire dataset was thoroughly appraised for initial observations of any recurring themes. The key Aboriginal organisations’ priorities and recommendations, identified during stage 2, were extracted into a spreadsheet and compared with the relevant final policy document. This included both reports of the committee overseeing the consultation process, which made recommendations to government, and the final government-endorsed policy documents. These documents were deductively analysed to identify the extent to which key food and nutrition issues and recommendations made by Aboriginal organisations were acknowledged and/or included. Key themes (identified in stage 2) were extracted into a table and cross-checked against committee recommendations and government actions in each policy/strategy document. Including both types of outcome document enabled more detailed analysis of whether Aboriginal perspectives had been considered and, where relevant, the point at which Aboriginal organisations’ recommendations appeared to fall off the policy agenda. A rating was applied  to each theme according to the degree of committee/government support for this policy priority. Ratings were discussed between a minimum of 2 investigators until consensus was reached. and the remaining 9 (between 2014-2018) were retrieved from government website searches. Stakeholder submissions were not publicly available for 8 policy processes. Nine had publicly-available submissions and were included in our stage one analysis. Five national food and nutrition policy processes were included in stages 2 and 3 of our analysis  were identified in the National Nutrition Policy Scoping Study,analysis . DetailsOf the 9 food and nutrition policy processes included in this analysis, 5 included at least 1 written submission from an Aboriginal organisation 55%; see . SubmissTwo of these policy processes were parliamentary inquiries (WIU and IOE), 2 were Government strategy development processes  and 1 was a National Health and Medical Research Council guideline development process (ADG). Six of the 9 policy processes with written submissions available occurred under a Labor  government and 3 under a Liberal-National (conservative) coalition government. Four of the 5 policy processes that included a submission from an Aboriginal organisation occurred between 2008 and 2011 under the Rudd/Gillard Labor Government and the fifth, a senate inquiry, occurred during the Turnbull Coalition Government see .The terms of reference for the committees (n = 8) overseeing food and nutrition policy processes revealed that of 75 committee members, none were identifiable from their public profiles as First Nations Peoples or representatives of Aboriginal organisations. In most cases, committee members were ‘appointed’ through expert committees or politicians in the case of parliamentary inquiries. Each committee had oversight from the sponsoring organisation, with 4 committees having government oversight, 2 with oversight by statutory (administratively separate from governments but funded by them) organisations, and 3 committees were directly overseen by parliamentarians . The majority of Aboriginal submissions (n = 7) were from the Aboriginal Community-Controlled Health sector (ACCHS). This included 4 Aboriginal health peak bodies and 1 Aboriginal health service. The remaining 4 submissions were from an Aboriginal health professional association, an Aboriginal-led advocacy coalition, an Aboriginal land council and an Aboriginal economic development organisation. One of the peak bodies made submissions to 4 of the policy processes. The most recent parliamentary inquiry (IOE) received a combined submission from Aboriginal health peak bodies.i) improve healthy food access and promotion, (ii) address the social determinants of nutrition, and (iii) strengthen governance of public health policy. The most common issues raised were: food insecurity (9/11), inaction on social determinants (8/11), multi-sectoral collaboration (9/11), and – almost unanimously (10/11) – the cultural appropriateness of interventions and services and self-determination. These are elaborated below using illustrative excerpts from submissions.less than 25% of their available income” within 10 years (NPHS 1d). Another organisation recommended:The recurrent issues raised in submissions regarding healthy food access and promotion, in descending order of frequency, were: food insecurity, capacity building, food subsidies and industry regulation. Limited access to affordable, nutritious food, particularly in remote areas was a key theme throughout the 5 policy processes. To highlight this point, submitting organisations cited statistics on the price differential of a standard basket of food between capital cities and remote Aboriginal communities. Food subsidies were frequently recommended to improve food access in remote areas. For example one submission recommended Government reduce the cost of a healthy food basket for Aboriginal families to “ Food subsidies should be highest for fruit and vegetables  but should also be extended to other food staples” .“ “strongly endorses a total ban on the advertising of junk food” . Food reformulation, including “ bans on the use of trans fats, reduction of allowable salt levels”  were also recommended, as well as “health-related taxes on sugary drinks and on ‘junk’ food” . This organisation recommended using tax revenue to subsidise healthy foods.Aboriginal organisations provided a range of suggestions for population-wide regulatory measures to reduce consumption of unhealthy foods. One submission build health promotion capacity in ACCHSs” . Suggestions for doing this included nutrition training for the Aboriginal health workforce and developing culturally relevant health promotion “resources which support healthy eating” .Aboriginal peak bodies opined that community-controlled health organisations frequently delivered effective, culturally-appropriate food and nutrition programs for Aboriginal communities, however lacked the long-term, funding and workforce capacity to sustain program delivery. They called on Government to “ addressing structural and environmental changes to improve nutrition status” . The individual risk factor approach was characterised as a Western paradigm, whereas Aboriginal models of health were described as comprehensive and holistic. Stakeholders urged cross-sector collaboration to improve social determinants such as education, employment and housing, and also emphasised  “racism, history, oppression and the ongoing impacts of dispossession” . One organisation stressed:The majority of Aboriginal organisations were critical of Government inaction on the social determinant of health. They highlighted that ‘behavioural’ approaches to nutrition promotion were favoured rather than “ “long-term efforts will be required for the creation of living environments that make healthy choices the easiest ones” . One of the most common determinants raised by Aboriginal organisations was the ineffectiveness of mainstream  health services. Submitters called for provision of culturally-appropriate comprehensive primary healthcare and a culturally competent workforce. Aboriginal organisations almost unanimously recommended:A commitment at all levels of government in terms of funding, policy development, and support for the implementation of culturally-appropriate programs and services” .“ “coordinated, whole-of-society approach”  to addressing food and nutrition issues. The importance of collaboration across agencies and across sectors was highlighted in most submissions as was the need for “genuine commitment, partnership and collaboration”  with Aboriginal organisations when planning multifaceted policy responses. Realising Aboriginal people’s right to self-determination was described as essential to policy success, with one organisation describing it as “ the foundation of true progress” . Almost all submissions emphasised the need for increased Aboriginal involvement in and, ideally, control of health policy decisions. For example:Aboriginal stakeholders advocated a Without exception, where Aboriginal people and communities lead, define, design, control and deliver services and programs to their communities, they achieve improved outcomes” .“ Outback Stores and the Northern Territory Community Stores Licensing Scheme. Similarly, committees were supportive of food subsidies and other regulatory strategies, but these were not recommended in final policies. Only the NPHS specifically addressed capacity building for Aboriginal health promotion and action on the social determinants of health; social determinants were merely acknowledged or completely absent in other policy documents. Also lacking from policy documents was support for culturally-appropriate primary healthcare programs and services, as endorsed in submissions. Finally, when it came to governance arrangements, policy recommendations generally supported multi-sectoral collaboration but self-determination was not acknowledged or recommend in any of the committee reports or policy documents. This is the first analysis of Aboriginal organisational engagement in Australian population-wide food and nutrition policy processes and the extent to which their perspectives are included in final policy documents. Findings suggest that, despite 10 years of advocacy to reduce health inequity and operationalise the right to self-determination, few Aboriginal organisations have participated in food and nutrition policy processes. Furthermore, as far as we could determine from this analysis of publicly available documents, none of the committees governing the consultation processes for the policies under analysis included Aboriginal people. From a political economy perspective, Aboriginal interests and ideas may have been limited by the colonial practice of excluding Aboriginal people from policy development and decision-making institutions of Government. Therefore, our analysis suggests that population-wide food and nutrition policy-making is culturally unsafe by design because it disempowers the self-determination of Aboriginal people. We elaborate on these concepts in light of our findings below. The concept, ‘interests,’ is concerned with the state of ‘power’ in policy debates. In our analysis, submissions from Aboriginal organisations represented <1% of all written submissions from organisations. Considering Aboriginal peoples comprise 3% of the total population in Australia, this demonstrates the under-representation of Aboriginal interests in population-wide food and nutrition policy debates. Across the 10-year period analysed and 17 policy processes identified, only 11 of the 1479 submissions made by organisations were from Aboriginal organisations. This may be because, although food and nutrition policy affects Aboriginal people, population-wide nutrition policy is not the core interest of these organisations. Nonetheless, food security and nutrition are key components of the holistic approach to improving health and well-being for Aboriginal people. The broader prevention scope of the NPHS (beyond nutrition) may explain why this policy process had the highest number of submissions from Aboriginal organisations (n = 5) as it may have been more aligned with the interests of Aboriginal Community Controlled Health Organisations.This includes whose interests are being served through policy-making, how resources are distributed and who stands to gain from this arrangement. Aboriginal organisations must also divide their time and attention between responding to national, state and territory policy processes regarding both Aboriginal-specific and population-wide issues to ensure their interests are equitably represented. It is possible that, after addressing Aboriginal-specific issues, there is little capacity to participate in other policy processes. In 2019 alone, approximately 20 Australian national population-wide health consultations were open for submissions. It is unlikely that Aboriginal Community Controlled Health Organisations would have the capacity to respond to every policy consultation process.Another possible explanation for the small number of Aboriginal submissions is the excessive burden of policy and administrative processes these organisations are required to participate in to remain accredited. Aboriginal organisations must compete against the larger, well-resourced and more numerous mainstream organisational and corporate interests. Industry interests frequently undermine public health actors in nutrition policy development. The power of industry interests in watering down public health recommendations in favour of agricultural prosperity was demonstrated during the development of the NFP. It has been suggested that public health nutrition actors have difficulty generating a cohesive, unified position to strengthen their voice over commercial and political interests. Our analysis suggests that Aboriginal organisations, as minority actors within public health, have limited power in the food and nutrition policy process to compete with these dominant interests. We suggest that this is not a “full realization…of ensuring participation of Indigenous peoples on issues affecting them” (UNDRIP Article 41). In the battle for scarce resources, majority interests can earn political favour more readily. Our findings suggest Aboriginal organisations consistently advocated for common ideas in their submissions . Despite well-organised actors, deeply embedded cultural orientations can form impenetrable barriers to changing policy development practices. For Aboriginal organisations, barriers include marginalisation, institutional racism and policy discourse based on deficits. It has been suggested that governments resist giving greater power to Aboriginal people as this could destabilise entrenched colonial ideas and practices. Furthermore, Aboriginal peoples’ “ideas” may not fit with “needs” as defined by Western policy-makers.Analysis of ideas seeks to understand how certain perspectives gain prominence in political debates. Transforming ideas into action requires coordinated, strategic communication deployed by actors with shared ideas about a particular issue. Previous research suggests that solutions focused on behaviour modification are more politically favourable for governments. The food industry provides strong opposition to ideas concerning regulatory strategies proposed by public health advocates. Our findings demonstrate that key ideas raised by Aboriginal organisations during the submission process also rarely penetrate food and nutrition policy. Although it was beyond the scope of this analysis to determine the extent to which the ideas proposed in non-Aboriginal organisations’ submissions influenced policy, the limited progress made by Australian governments in implementing population-wide food policy actions recommended by public health advocates, suggests that this issue is not limited to Aboriginal organisations.Aboriginal organisations frequently recommended structural and environmental strategies in their consultation submissions, but policy documents were more likely to recommend behavioural approaches. It is argued that a focus on behavioural deficits in Aboriginal policy is part of the enduring legacy of forced assimilation and ongoing colonisation. Furthermore, the committees reviewing stakeholder submissions before making recommendations to government are almost entirely comprised of non-Aboriginal people, and the process of writing and editing is opaque. This increases the likelihood that Aboriginal voices will be filtered out in institutional decision-making processes. Australia’s National Health and Medical Research Council has recently proposed including at least 2 Aboriginal representatives on all future guideline development committees.The findings of this research suggest that the institutional arrangements for participation in national food and nutrition policy processes structurally disadvantage Aboriginal organisations. Aboriginal organisations, like all external stakeholders, participate in policy processes by making submissions and participating in consultation meetings. In many cases, these processes were overseen by a government-appointed standing committee (with no clarity on the selection criteria). This research identified that written submissions were the most common consultation method in food and nutrition policy and these had limited Aboriginal participation. Alternative methods such as round tables, public hearings, public meetings, and workshops were held for some policy processes but were not consistent across the policy episodes. The process of requiring written submissions to participate in policy decisions is a colonial institutional practice that may be inconsistent with Aboriginal oral communication styles where cultural values are infused. However, the findings of this research suggest that, despite increasing engagement and participation of Aboriginal organisations in Aboriginal-specific policy-making, when it comes to population-wide policy processes, Australian governments, irrespective of the political party in power, have been less successful at operationalising the right to self-determination. While Aboriginal-specific policy stresses self-determination and cultural safety as central to policy formulation, population-wide food and nutrition consultation mechanisms exclude the cultural ideas and interests of Aboriginal people.According to the United Nations Declaration on the Rights of Indigenous Peoples, to which Australia is a signatory, First Peoples have the right to participate in decision-making regarding all matters that affect them; this includes both Aboriginal-specific and population-wide policy. The institutionalisation of this domestic human rights instrument is cited as a key factor underpinning the relatively lower levels of Indigenous health inequity in New Zealand compared with Australia. Unlike New Zealand, Australia does not have dedicated seats in its national parliament for representation of First Peoples. In fact, the first (and only) 2 Aboriginal members of the Australian House of Representatives were elected during the period under analysis, in 2010 and 2016. The Uluru Statement from the Heart is a consensus statement from Aboriginal Australia which advocates for a constitutionally-enshrined voice to Parliament so that Aboriginal people can have a consistent voice on all policy decisions that affect them. This research provides further evidence for the need for an Aboriginal voice to be embedded within policy-making institutions in Australia.In contrast to Australia’s absence of a treaty with its First Peoples, the New Zealand treaty of Waitangi binds the New Zealand government to consider Māori rights to self-determination in all policies, enabling Māori to maintain a direct voice to parliament. Came et al found in New Zealand that, despite the Treaty of Waitangi, the knowledge and interests of Māori and Pasifica leaders were devalued in policy participation processes. Our analysis of Australian policy processes found that arguments about social determinants of health, cultural appropriateness and self-determination were excluded from the policy agenda. The complete absence of Aboriginal people from population-wide national food and nutrition committees over a 10 year policy trajectory affirms the Australian norm of ‘legal invisibility’ of Aboriginal people in Australian policy-making, and recreates institutional inequity in policy responses.It is through Aboriginal participation that cultural values, needs and preferences for action can be reflected in policy development processes through to strategic documents and government actions. Our research reveals the exclusion of Aboriginal people from the committees overseeing the development of food and nutrition policy actions and the marginalisation of Aboriginal interests and ideas in policy documents. Māori scholar, Dominic O’Sullivan argues that the democratic expectations of First Nations peoples are conditioned by colonial experiences. An attitude that diminishes or disempowers Aboriginal cultural identity can create an environment that is alien, culturally unsafe and a dangerous place for First Nations peoples to be. Our findings demonstrate the need for critical reflexivity in the institutional design of policy development processes so that they are culturally inclusive and address power imbalances and, thereby, enable genuine participation of Aboriginal peoples and culturally safe food and nutrition systems.We found that the vast majority of submissions in population-wide food and nutrition policy processes were from non-Aboriginal organisations. Along with the membership of oversight committees consisting of non-Aboriginal experts, civil servants and politicians, and the control of the policy process by governments, politicians and government statutory organisations, this indicates the dominance of non-Aboriginal voices in the legitimation of knowledge, decisions about who makes the rules and where resources are allocated. This institutionalised attitude runs contrary to establishing participatory systems and processes through which Aboriginal people can express self-determination.; however, these were not included in the current analysis as it was difficult to capture who attended these meetings. Furthermore, we focused on formal mechanisms of participation and acknowledge the influence of informal networks of influence through which Aboriginal peoples influence heath policy. Thus, we cannot be certain that we have captured all of the Aboriginal perspectives presented in food and nutrition policy debates. Despite this limitation, our findings indicate that participation of Aboriginal organisations in national population-wide food and nutrition policy processes has been limited.This research has several limitations. First, it is possible that some Aboriginal policy submissions were missed if the organisation requested that it not be made publicly available. Aboriginal organisations may have also contributed through other consultation mechanisms such as roundtables public meetings and informal networks Another limitation is that we were unable to attribute the actions recommended in policy documents exclusively to the submissions made by Aboriginal organisations. It is possible that non-Aboriginal organisations were also advocating for similar issues such as food security and regulatory policies. The submissions made by other organisations have not been examined for comparison. Additionally, the inclusion of recommendations in policy documents does not guarantee that these will be implemented in practice. Future research should examine the full range of stakeholder perspectives and the extent to which policy recommendations are implemented by governments. Our population-wide focus meant that we did not analyse participation in food and nutrition policies targeting Aboriginal people, where engagement would likely be greater.The focus of this analysis was national-level, population-wide food and nutrition policy. This does not capture the full extent of Aboriginal participation in food and nutrition policy-making processes in the Australian context. State and Territory governments develop their own health policies, including food and nutrition; however, analysis of the degree to which Aboriginal people have participated in these policy processes was beyond the scope of the current study. Furthermore, Aboriginal and Torres Strait Islander health is a discrete area of national health policy, which operates in parallel with population-wide food and nutrition policy processes.i) very few Aboriginal organisations have participated in national, population-wide food and nutrition policy processes; (ii) common and consistent themes in Aboriginal organisations’ policy submissions included food insecurity, culturally-appropriate programs, multi-sectoral collaboration, capacity building, social determinants, and Aboriginal peoples’ right to self-determination; and, (iii) Aboriginal recommendations were seldom addressed in final policy documents. These findings indicate existing population-wide food and nutrition policy processes are culturally unsafe and systematically disadvantage Aboriginal Australians. With regard to population-wide food and nutrition policy, Australia is not meeting its obligations under the United National Declaration on the Rights of Indigenous Peoples. Our analysis could be replicated across other public policy areas in order to further evaluate the implementation of this human rights framework. Alternative policy-making mechanisms are required to adequately address Aboriginal interests and ideas and enable self-determination in the area of food and nutrition. The Uluru Statement from the Heart provides a moral and human rights imperative for improving governance arrangements for Australia’s First Peoples.This research has demonstrated that over a 10-year period in Australia: .1Global Obesity Centre, Institute for Health Transformation, Deakin University, Geelong, VIC, Australia. 2School of Health and Social Development, Deakin University, Geelong, VIC, Australia. 3Committix Pty Ltd., Newcastle, NSW, Australia.


Climate change is increasing the intensity, duration, and frequency of extreme climate events (ECEs). These ECEs can have major ecological consequences, e.g., changing nutrient flows, causing extirpation, and altering organismal development. Many ECEs are discrete events that occur at distinctive times during the biological processes they impact. Because of this, ECEs are likely to have differing ecological impacts depending on when they happen, yet we lack on studies that explore how the ecological consequences of ECEs vary with when they occur. Drawing upon evidence from physiological, population, and community ecology, and previous work on ecological disturbances, we suggest that the consequences of ECEs will be sensitive to when they occur. We illustrate the importance of timing by showing how the effects of an ECE could vary depending on when it occurs through the course of (1) organismal ontogeny, (2) population dynamics, and (3) community assembly. An enhanced focus on the timing of extreme weather in climate change research will reveal how and when ECEs are altering ecosystems, possible mechanisms behind these impacts, and what ecosystems or species are most vulnerable to ECEs, helping us to make more informed predictions about the ecological consequences of climate change. Extreme climatic events (ECE) are increasing in intensity, frequency, and duration globally. We present evidence that the ecological consequences of ECEs are highly sensitive when they occur during the progression of biological processes at each of these scales. In this section, we discuss how the ecological consequences of an ECE will depend on the current ontogenetic stages and states of the organisms present in the community when and where the ECE occurs Figure . ExtremeMyzus persicae) depend on aphid age  experience heat events their lifetime fecundity and longevity depend on their life stage during the event  if the event happens during the early stages of development but not later in ontogeny  and goldenrod (Solidago canadensis), high heat events have opposite effects on photosynthetic rates and productivity depending on the plant stage  have a positive relationship between age and chemical defense concentrations, and a negative relationship between age and water and nitrogen concentration  led to a 21% decrease in the number of hatched eggs produced by females with resulting population changes  in Madeira, Portugal, was able to recover quickly from a mass‐mortality event in part because it occurred immediately after the urchin's spawning period (egg‐releasing period). While adults died in mass, the larvae were resistant and contributed to a rapid population recovery  recovered their population size a year after the event through compensatory breeding  show rapid phenotypic adaptation over short time scales ; investigation (lead); methodology ; project administration ; resources (lead); writing – original draft (lead); writing – review and editing . William C. Wetzel: Conceptualization ; methodology ; project administration ; supervision (lead); validation (lead); writing – review and editing (lead).Both authors declare no conflict of interest.Funding was provided by the Michigan State University T. Wayne and Kathryn Porter Graduate Fellowship Endowment Fund., Ecology, Summer fellowship in Evolution, and Behavior, and Summer Critical Needs fellowship.


A receptor plasticity in the pathophysiology of PPD. We also discuss evidence supporting the efficacy of brexanolone for the treatment of PPD, which opens a promising new horizon for neurosteroid-based therapeutics for mood disorders.Postpartum depression (PPD) is a debilitating psychiatric disorder characterized by a high worldwide prevalence and serious long-term negative outcomes for both mothers and children. The lack of a specific treatment and overreliance on pharmacotherapy with limited efficacy and delayed treatment response has constituted a complication in the management of PPD. Recently, the Food and Drug Administration (FDA) in the USA approved a synthetic formulation of the GABAergic neurosteroid allopregnanolone, administered intravenously (brexanolone) for the rapid, long-lasting and effective treatment of PPD. Hereinafter, we review findings on allopregnanolone biosynthesis and GABA Postpartum depression (PPD) is a subtype of major depressive disorder that affects around 6.5–12.9% of puerperal women every year . In addiA receptor function in the pathophysiology and treatment of PPD.This article will focus on the promising new horizon opened by neurosteroid-based treatment for depressive disorders by discussing the role of neurosteroids interfacing with GABAStress plays a major role in both the presentation and severity of PPD and the inability to shut down the stress-induced hypothalamus–pituitary–adrenal (HPA) axis activation has been traditionally suggested as an underlying neurobiological mark of PPD. The GABAergic signaling modulated by neurosteroids, including allopregnanolone and its equipotent GABAergic isomer, pregnanolone, may play a role in some of this disorder manifestation , 9, 10. The biosynthesis of allopregnanolone and pregnanolone has been associated with the emergence of depressive disorders and post-traumatic stress disorder (PTSD) –14. AlloA receptor neurotransmission, including altered expression of the receptor subunits and impaired neurosteroid biosynthesis  and indices of anxiety during pregnancy showed that lower progesterone and combined measures of allopregnanolone + pregnanolone were associated with greater negative emotional responses to stress, and lower cortisol was associated with worse sleep quality. These data suggest that progesterone and allopregnanolone + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and acute stress challenges appear to reduce these steroids to promote negative emotional responses .Finally, a study demonstrated altered sensitivity to neuroactive steroids specifically in patients presenting a history of PPD . This inThese studies  blockade in pregnant rats, which reduced both plasma and brain allopregnanolone content and prevented the decrease of γ2 mRNA expression observed during pregnancy. Furthermore, these subunit changes resulted in structural and functional changes in the GABAA receptor demonstrated by decreased stimulatory effect of the GABAmimetic drug muscimol on Cl− uptake by cerebrocortical membranes. These observations support a role for allopregnanolone in regulating the plasticity of GABAA receptor-containing γ2 subunit during pregnancy and after delivery , GABA Therapeutics, and NeuroTrauma Sciences . He has two patent applications, one on N-palmitoylethanolamine (PEA) and peroxisome proliferator-activated receptor alpha (PPAR-α) agonists US20180369171A1, pending, and one on allopregnanolone analogs US11266663B2 granted on March 8, 2022 in the treatment of neuropsychiatric disorders. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


High expression levels of the TTK gene are closely related to tumor occurrence and poor prognosis, as confirmed by some studies. Our study explored the prognosis of lung adenocarcinoma (LUAD) patients with different TTK levels and the possible pathological mechanism of TTK in LUAD.We extensively searched literature databases and high-throughput sequencing databases and included relevant literature or datasets in the meta-analysis according to the inclusion and exclusion criteria. Hazard ratios (HRs) and 95% confidence intervals (CIs) related to TTK expression were calculated, publication bias was assessed, and sensitivity tests were performed. We also compared the relationship between cancer immune infiltrating cells and tumor mutation burden (TMB) in patients with different TTK expression levels via bioinformatics analysis. The half maximal inhibitory concentration (IC50) of some chemotherapeutic and targeted therapy drugs were calculated. The potential biological functions or pathways associated with different TTK expression levels were determined by gene set enrichment analysis (GSEA).The meta-analysis revealed that higher TTK expression level was significantly associated with poor prognosis in LUAD patients, both in overall survival (OS) and progression-free survival (PFS). The expression level of TTK was significantly correlated with presence of some immune cells and TMB. Tumors with higher TTK expression levels were mostly enriched for the cell cycle, DNA replication and homologous recombination pathways. In addition, patients with different TTK expression levels were differently sensitive to some antitumor drugs.TTK may be a promising prognostic biomarker for LUAD and is worthy of further investigation. Among cancers, lung cancer is the leading cause of cancer death in men and women. Lung cancer in patients without a history of smoking should not be underestimated and is expected to cause 20,420 deaths  study type: prospective or retrospective cohort study; (2) participants: patients with pathologically diagnosed LUAD expression of TTK in tumor tissues; and (3) outcome data: overall survival (OS), progression-free survival (PFS), and OS and PFS hazard ratio (HR) and 95% CI data, or sufficient data to enable calculation of these outcomes. Literature exclusion criteria included (1) nonoriginal studies such as reviews, conference summaries and case reports; and (2) animal experiments or cell experiments. If multiple studies with the same content were identified, the most recent and most complete study was used. In addition, we also searched two public databases, The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, for sequencing data and clinical information. These two databases were employed to calculate the expression of TTK and its relationship with the OS and PFS of LUAD patients.2.2.Two researchers searched the literature independently, screened the literature according to the inclusion and exclusion criteria, and extracted the data from the screened literature. The main data extracted were the HR and 95% CI values related to OS and PFS. If there were different opinions, they was discussed by the two researchers, or a third researcher made the decision. The limma . The NOS scoring system includes three aspects: study object selection, intergroup comparability and result measurement, for a total of 8 items  is an online analysis tool for estimating gene expression profiles and estimating the percentage of cell types in mixed cell populations using gene expression data  of common chemotherapeutic and targeted therapy drugs in the Cancer Genome Project (CGP) data of the LUAD dataset via the pRRophetic package  analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to reveal the potential biological functions or pathways associated with high levels of TTK expression. For biological process (BP), high TTK expression levels were mostly enriched in cell cycle checkpoints, cytokinesis and DNA repair I. For ce4.In our study, we explored the influence of the TTK gene on the prognosis of LUAD patients, although we did not find any available literature after an extensive search of relevant literature databases. However, we obtained relevant data from TCGA and GEO databases for individual patient data (IPD) meta-analysis and found that high expression of TTK leads to poor prognosis. At the same time, we used clinical information in the TCGA database to construct a nomogram to prove the application of TTK in clinical prognosis. In addition, we also explored the relationships between the expression level of TTK and immune cell infiltration and antitumor management. The expression level of TTK is positively correlated with TMB, and the expression level of TTK is correlated with patient sensitivity or resistance to some antitumor drugs. Therefore, TTK is likely to become a LUAD tumor therapeutic target and prognostic marker.The TTK gene, located on chromosome 6Q13-Q21, encodes serine/threonine and tyrosine protein kinases, which are doubly specific protein kinases  antibody inhibited tumor growth at a well-tolerated dose (Mason et al. Our research still has some limitations. First, our meta-analysis is an IPD meta-analysis, not a conventional meta-analysis; our data were not limited to published data but we obtained the most original data, which greatly reduces the common publication bias and heterogeneity in conventional meta-analyses. However, our study was a retrospective analysis, and some confounding factors may not be corrected. Second, although we preliminarily explored the biological process of TTK in LUAD through GSEA, the detailed mechanism linking TTK expression with the pathological progress of LUAD needs to be verified by further biomedical experiments. However, the current results are encouraging and deserve attention in identifying promising predictive biomarkers of LUAD.5.A high expression of TTK is related to poor prognosis in patients with LUAD. In addition, the expression level of TTK is correlated with some tumor infiltrating cells and is positively correlated with TMB. The expression of TTK in patients with LUAD may be related to the resistance to some antitumor drugs.


The certainty of evidence remained at a low level for all (n 11) studies due to the cross-sectional, observational nature of studies. Three major themes emerged: (1) food environment, (2) student perceptions (SPs), and (3) dietary outcome (DO). In a university food environment, the taste of food was paramount for the food choices of students, followed by the availability of food and the price of food. When university students perceive and choose foods and beverages, they sometimes regard unhealthy foods and beverages as healthy options. The diet quality of university students is more susceptible to living arrangements and socioeconomic status, but higher salt, fat, and added sugar consumption generally resulted in poorer quality of diet on campus. Future research could use novel methods to explore a wider range and deeper level of students' dietary behavior determinants in university food environments.The food environment has been implicated in creating an obesogenic generation; and while previous research has focused on population-wide initiatives, the university population resides in a research gap. To explore detailed components of the university food environment and what shaped dietary behaviors, we retrieved literature from the following databases: ScienceDirect, Scopus, PubMed, Medline, and EMBASE. Eleven studies were identified for qualitative content analysis and study quality assessment identified most of the studies as of good quality (https://www.crd.york.ac.uk/prospero/, identifier: CRD42021283562. Non-communicable diseases (NCDs) are statistically responsible for 71% of global deaths with unhealthy diet listed as one of the five major risks for NCDs . ObesityMuch effort has focused on investigating the effect of the food environment on dietary behavior and health status in different settings –16. BesiUnlike secondary schoolers, young adults enrolled in tertiary educational institutions living away from home are no longer under strict family supervision for daily dietary intake. According to student accommodation surveys, the proportion of university or college students living at home with parents was as low as 10 to 16% , 30. StuThe current review aims to explore whether the university food environment influences university students' dietary behaviors, and to understand how university students perceive their food environment. In particular, we investigate evidence on how specific components of the university food environment impact food choices, dietary intake, eating behavior, and diet quality of students.The systematic review was conducted according to the PRISMA 2020 Guidelines , adaptedIn order to select relevant articles, the following inclusion criteria were applied: randomized controlled trials (RCTs), pre- and postintervention studies, quasi-experimental studies, cross-sectional studies, and other non-experimental or pragmatic design studies; participants studied for their outcomes in a tertiary education setting; primary outcomes included measures or changes to dietary behavior; and studies targeted at students attending university/college. The inclusion criteria are fully detailed in Conducting and reporting this systematic review was based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement . The PRIBasic logic for database search strings included four domains: (1) one domain defining the study as university setting; (2) one domain indicating food environment as the influential factor; and (3) two domains investigating dietary behavior as the outcome. Boolean operators and MeSH terms were incorporated into the search strategy when appropriate. n 14) for review and reached a consensus on the final list (n 11). Out of the three studies not included, two were excluded because they were only concerning interventional outcomes rather than food environment measurements  and qualitative focus group discussion (n 2). Results were analyzed using an interpretive content analysis approach where the researchers reviewed and coded the results. Thematic categories were generated and combined after each iteration and researchers were finally in consensus with major themes.Although all included studies were cross-sectional observational studies, significant heterogeneity in country settings, sampling design, and outcome measures meant that data could not be pooled for a meta-analysis. Most of the literature included mixed quantitative/qualitative research focusing on food fact questionnaires  was reached after a thorough assessment of study contents: all were cross-sectional studies with survey design (n 9) and focus group discussion (n 2) methodology. Three studies were determined to be of a very-low level of certainty due to their lack of essential quality assurance measures within study design and conducting, other eight included studies remained as low-level evidence. Details of the assessment are summarized in Initial screening for title and subsequent abstract review identified 381 articles for further full-text examination. The exclusion of articles was decided with care since we wanted to extract as much evidence as possible on this understudied area. A final list (n 5); studies (n 4) fell under the SPs of the university food environment theme; and DO theme-related studies (n 6) that looked at the exposure to such food environments and its impact on dietary behaviors of participants.The characteristics of included studies and their primary contribution to this review have been tabulated in Five cross-sectional survey-based studies commented on the university food environment that students were exposed to. Two studies performed detailed food environment audits to assess food outlets and vending machines on the products sold, while the remaining three studies employed relatively more subjective responses or collective descriptions for food environment evaluation. However, audit results were contradicting: Martinez-Perez et al.  identifiVan den Bogerd et al.  collecteA considerable proportion of students' dietary intake took place outside the campus wall in non-campus nearby stores, especially for those living off-campus . CompareIn addition to the food environment created by university food outlets and what was available at the outlets, cultural norms and peer influences were found to change DPs of university students, particularly for those from a different background . In thisOut of the four studies that focused on the perceptions of students on their food environment, two used focus groups whereas the other two used cross-sectional survey-based methods. All studies concluded that taste was the most important factor when they made food and drink choices. Block et al.  reportedFollowing taste, three factors were frequently placed on responses of the students: value for money, convenience/availability, and nutrition value. Price could be placed as the second most important influencing factor but the dominance of taste over price was clearly identified and a lower price only mattered if taste was not compromised for less cost . NutritiIn the included studies, gender difference also appeared to influence factors defining dietary behavior of university students. Among participants of Hebden et al. , higher Six cross-sectional survey-based studies reported on the outcomes of dietary behaviors of university students. Two of the six studies introduced DPs as an outcome measure to assess student dietary intake. Fonseca et al.  providedn 43), lived away from home but in Greece (n 37), and lived away from home in UK (n 55). Students who remained in Greece did not show significant alterations in their dietary behaviors, whereas those who moved to the UK changed their routine diets. Although the authors attributed such observation to a general difference between the Northern European dietary environment and the Mediterranean one, no in-depth analysis of the food environment differences was conducted within this study.In another study employing DPs to measure student DOs, Kremmyda et al.  comparedVan den Bogerd et al.  measuredIn addition to fruit and vegetable intake, Kourouniotis et al.  found thIn two studies concerning the frequency of food purchase on campus, more than half participants reported consuming five or more foods and/or beverages on campus per week regardless of gender , 60. WheOverall, the university food environment impacts dietary behavior of students mostly in unfavorable ways to ultimately cultivate an unhealthy eating style –59. StudThe university food environment has been characterized by low availability of healthy foods and higher cost compared to unhealthy options –65. WhenWhen university students, or young adults who were primarily 18 to 30 years old, reported their purchase determinants within the university food environment, they considered taste as the paramount factor for dietary options, followed by cost and availability , 54, 55.n 112 and 35, respectively) and employed methods that were relatively weak in reliability, implementing the risk of participant expectation bias  or focus group (n 2). All included studies (n 11) employed convenience sampling methods, which could potentially reduce the representativeness of the sample and hence lower reliability. The association between university food environment and student dietary behavior still lacked high-quality longitudinal study to provide stronger support.However, some limitations should be noted. Study heterogeneity has been found in studies on food environment, particularly when it was associated with dietary behavior under diverse university settings. Among included studies, only one study claimed to have collected longitudinal cohort data but only with two timepoints , while oConfounding was lower-ranked on the priority list of consideration among studies and may or may not be evident enough to confirm the association between university food environment and dietary behavior of the student. The effect could have been hindered among the vast variety of factors influencing dietary behavior in a real-world university setting . HeterogSubjective perceptions of the food environment from students could be as important as or even more important than the options they are exposed to but unfortunately was often overseen in some studies attempting to answer the question of what shaped their dietary behavior. Non-geographical features affecting the accessibility to food options of students were one of the factors unexplored in current methods . DetermiPhotographic and audio/video sampling from participants, especially young adults, could be a valuable tool for researchers to synthesize themes that participants might not even be aware of. Photographic food record assessment has been employed to measure dietary intake, although this method was found inaccurate among populations with distinct characteristics . The valFood environment factors promoting stress eating and unhealthy food options more accessible to susceptible stress eaters could be the future interest of investigation. Further research should focus on determining the potential for long-term food environment interventions and collect reliable longitudinal data to assess whether modifications to the university food environment impact student dietary behavior. The university staff population was understudied for their dietary behavior within the university food environment. Comparison and contrast of staff and student population who were significantly different in demographic characteristics could indicate the critical relationship between the food environment and how dietary behavior is affected.Controversial opinions on the impact of individual behavioral factors on dietary behavior among university students indicate further research to understand more on this aspect. Morin et al. commented on factors that could shape the dietary behaviors of individuals including fear of social isolation and altruistic motives such as sustainability awareness . In the Significant factors determining food choices and eating habits of university students include taste, value for money, and accessibility of foods and beverages. Hence, interventions targeting the availability, accessibility, and cost of these unhealthy and healthy foods could be influential for obesity control among university students, particularly the first-years. Current results rarely report on sociocultural factors influencing the dietary behavior of university students. Future research is warranted on the collection of longitudinal data with revised methods to allow participants to demonstrate a more comprehensive picture of how the university food environment has shaped their dietary behavior.The original contributions presented in the study are included in the article and XL and RR: conceptualization, methodology, and formal analysis. XL, RR, AB, and ZL validation. XL: writing the original draft preparation and visualization. RR, AB, and ZL: writing, reviewing, and editing and supervision. RR and ZL: project administration. All authors have read and agreed to the published version of the manuscript.This study was funded by Internet Plus Clinical Nutrition Teaching Modes Innovation of Hebei Medical University, China [grant number: 2020YBZD-7] and Internet Plus Clinical Nutrition Teaching Modes Innovation of Hebei Education Department, China [grant number: 2020GJJG122].The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


A key element of risk assessment is accounting for the full range of variability in response to environmental exposures. Default dose-response methods typically assume a 10-fold difference in response to chemical exposures between average  and susceptible humans, despite evidence of wider variability. Experts and authoritative bodies support using advanced techniques to better account for human variability due to factors such as in utero or early life exposure and exposure to multiple environmental, social, and economic stressors.This review describes: 1) sources of human variability and susceptibility in dose-response assessment, 2) existing US frameworks for addressing response variability in risk assessment; 3) key scientific inadequacies necessitating updated methods; 4) improved approaches and opportunities for better use of science; and 5) specific and quantitative recommendations to address evidence and policy needs.Current default adjustment factors do not sufficiently capture human variability in dose-response and thus are inadequate to protect the entire population. Susceptible groups are not appropriately protected under current regulatory guidelines. Emerging tools and data sources that better account for human variability and susceptibility include probabilistic methods, genetically diverse in vivo and in vitro models, and the use of human data to capture underlying risk and/or assess combined effects from chemical and non-chemical stressors.We recommend using updated methods and data to improve consideration of human variability and susceptibility in risk assessment, including the use of increased default human variability factors and separate adjustment factors for capturing age/life stage of development and exposure to multiple chemical and non-chemical stressors. Updated methods would result in greater transparency and protection for susceptible groups, including children, infants, people who are pregnant or nursing, people with disabilities, and those burdened by additional environmental exposures and/or social factors such as poverty and racism. A critical element affecting the accuracy and usefulness of chemical risk assessment is accounting for the full range of individual and population variability in response to environmental chemical exposures. There are four stages of risk assessment, including 1) hazard characterization, (2) exposure assessment, (3) dose-response modeling, and 4) risk characterization. Although it is important to characterize variability in exposure, dose-response, and risk, this paper focuses on the importance of characterizing variability in the dose-response relationship between a chemical and health outcome as a critical part of predicting population health risks for both cancer and non-cancer health risks. Issues regarding the underestimation of exposure variation are discussed in more detail by Vandenberg et al. in the special topics companion paper. Fully describing human variability is a necessary step towards ensuring the protection of everyone, including those most susceptible and highly exposed. Understanding those who are in the highest exposed group and/or who are most affected can help target interventions and policies that protect those most at-risk and subsequently the whole population. While many intrinsic and extrinsic factors, including age/life stage of development, genetics, underlying physiological function, and socioeconomic status (SES), can either separately or together enhance individual susceptibility and affect population variability in response to chemical exposures  pyrene, TCE, and other air toxicants among susceptible age groups  . AdditioScience and Decisions [Due to the significant body of scientific evidence supporting the need for greater public health protection among susceptible and highly exposed populations, we recommend that as a first step, the default adjustment factor for intra-species variability used by the US EPA should be increased to a minimum of 42X, unless there are robust chemical-specific data to the contrary. This is supported by the 42X IPCS estimate of human variability, which relied on high-quality TK and TD data, with the limitation of primarily focusing on healthy adults , 99. It ecisions , 125. ThBased on the scientific literature , 15, 16 Separate adjustment factor to address age-related susceptibility. This approach is supported by evidence demonstrating that the current default approach does not protect the human population across life stages of development when considering age-specific differences, such as decreased metabolic clearance of pharmaceutical chemicals among developing fetuses and young infants compared to adults [We further recommend adoption of a separate adjustment factor for age/life-stage differences, which is supported by the IPCS and OEHHA analyses described above , 90. Alto adults   that would account for exposure to multiple chemical and non-chemical stressors , 67. ThiWhen sufficient data are available, estimating disease risk in a population that is representative of the general population and/or susceptible subgroups can better account for variability in a specific response. The method of Ginsberg 2012  can help, in silico) to quantify overall and category-specific human population variability in chemical risk assessment. The incorporation of new data could serve to update generic default probability distributions for TK and TD variability that were established by the IPCS in 2014 [We recommend that agencies adopt probabilistic approaches that integrate multiple heterogeneous data sources  to update overall  and/or category-specific  human variability, as described by Axelrad et al. . MoreovePrevious publications assessing the default factor of 10X have provided useful perspectives on the sufficiency of a 10-fold adjustment as well as methods to evaluate the extent of human variability. To ensure greater transparency in assessments of human variability, we recommend the formal use of the University of California San Francisco’s (UCSF’s) Navigation Guide systematic review framework , or anot, pregnant people, lactating people, people with disabilities, and other susceptible subgroups) would ultimately achieve overall population benefits for all.In summary, current data  show that the approaches used to incorporate human variability in hazard and risk assessment need to be updated to reflect current science. The US EPA should improve its risk assessment practice by adopting a higher and more accurate default point estimate adjustment factor for inter-human variability and potential separate adjustment factors for age-related and external sources of variability. The agency should also advance risk assessment research and practice by implementing probabilistic approaches that integrate information across multiple complex data sets. Updated approaches that integrate multiple data sources would improve estimates of human variability and provide more adequate protection for susceptible subgroups, such as pregnant people, developing fetuses/neonates, children/adolescents, low-wealth populations, and those burdened by additional occupational and/or environmental exposures. Protective approaches for susceptible groups (e.g.


Animal welfare considerations with the 3R principles, Replacement, Reduction, and Refinement (3Rs), have become more important in regulatory toxicity testing. Modifying OECD inhalation toxicity test guidelines 412 and 413 aim to minimize animal use and maximize the number of endpoints that are measured for bronchoalveolar lavage fluid and lung burden measurement in toxicokinetics studies.The OECD test guidelines for animal experiments play an important role in evaluating the chemical hazards. Animal tests performed using OECD guidelines, especially when the good laboratory practice (GLP) principle is applied, reduce the duplication of toxicity testing and ensure the best mutual acceptance of data by the OECD’s Mutual Acceptance of Data (MAD). The OECD inhalation toxicity test guidelines 412 (28 days) and 413 (90 days) have been revised. These OECD guidelines now reflect the inclusion of nanomaterials and recent scientific and technological developments. In particular, these test guidelines aim to evaluate the bronchoalveolar lavage fluid in the lungs for objective toxicity evaluation, along with the existing subjective histopathological evaluation. For solid particles, the lung burden measurement of particles is required for toxicokinetic studies and, in order to properly perform a toxicokinetic study, two post-exposure observations are recommended. In light of the revised OECD guidelines, we propose a method to reduce the number of animals when testing is conducted for nanomaterials. The OECD Test Guidelines (TGs) for testing chemicals are a collection of the most relevant internationally agreed testing methods used by governments, industry, and independent laboratories to assess the safety of chemicals. The TGs detail the procedures for regulatory safety testing, chemical notification, and registration. As scientific progress and country regulations continue to evolve, so do the TGs. Another component of OECD TGs is the mutual acceptance of data (MAD), which helps to address governmental requirements and provides a basis for cooperation among national authorities .One of the critical principles of the experimental testing of chemicals is called Good Laboratory Practice (GLP), and ensures experimental data quality and integrity . Those aThe OECD revised the test guidelines for the existing inhalation toxicity tests to reflect the emergence of nanomaterials and recent scientific trends. In particular, the objective pathological evaluation was made mandatory by the addition of bronchoalveolar lavage fluid (BALF) analysis, breaking away from the dependence on subjective histopathology in the existing inhalation toxicity test evaluation. In addition, the revised test guidelines required measurements of the test article to be taken in real-time, along with off-line aerosol measurements in an inhalation chamber, reflecting the latest technology for the characterization of nanomaterials. Furthermore, the revised test guidelines (TG 412 and 413) require lung burden measurements to be conducted for solid particles during post-exposure observation periods to evaluate the lung clearance kinetics of the solid test particles [In regulatory testing, the principle of Replacement, Reduction, and Refinement (3Rs) with REACH Article 4 of Directive 2010/63/EU states that “The Member States shall ensure that the number of animals used in projects is reduced to a minimum without compromising the objectives of the project”, and Article 13 states that “In choosing between procedures, those which to the greatest extent meet the requirements of the use of the minimum number of animals” . We summThe current OECD TGs for inhalation toxicity testing 412 (28-day) and 413 (90-day) were recently revised to evaluate lung inflammation with objective measurements as well as to assess the lung burden of insoluble nanomaterials. Subsequently, additional animals are required for use immediately after termination of exposure for post-exposure observation periods to conduct bronchoalveolar lavage (BAL) fluid analysis and lung burden measurements. Measuring these variables, however, increases the number of testing subjects to 120 for TG 412 and 160 for TG 413, which is a large increase in testing subjects when compared to earlier testing guidelines . Regarding the test article exposure system, whole-body-type exposure chambers may require an increase in chamber volume to meet the requirement that “the total volume of the test animals should not exceed 5% of the chamber volume.” Nose-only-type chambers need more exposure ports, which can lead to an investment of capital by researchers. OECD recognizes this burden and seeks high quality and cost-effective research .Recent inhalation studies by our group suggest that animal use in the test guideline studies can be minimized while maximizing the number of measured endpoints. A closer look at rat lung anatomy provides a useful opportunity to consider fewer animals that follow TG 412 and TG 413. The rat lung has five lobes: four lobes in the right lung  and one lobe in the left lung . We propNanoparticle testing provides evidence for this proposed approach. Nano-objects provide a test material that can be confidently measured in the lungs. In the subacute inhalation study with soluble silver nanoparticles (AgNPs) and insoluble gold nanoparticles (AuNPs), Park et al.  and Kim As we expressed above, the even lobar deposition of fibrous nanomaterials such as carbon nanotubes and plate-shape nanomaterials such as graphenes has not been studied to date. However, recent work by Devoy et al.  and Kim We believe that careful consideration of the lung tissues of each animal will lead to a reduction in the use of animals and maintain experimental integrity. To comply with TG 412 and 413, lung burden measurement is needed to derive clearance kinetics, and tissue distribution. Organs other than the lungs are used for both histopathological assessment and analytical chemical evaluation, assuming proper study design. We believe that toxicokinetic assessment, at least for nanomaterial inhalation exposure, can be conducted within the framework of current TG 412 and 413 with three sampling timepoints. Several considerations regarding the revision of toxicokinetic test guidelines are considered and include: (1) the number of samples for analysis and (2) analytical timepoints considering animal welfare and kinetic derivation. Based on our laboratory experiences and the literature, obtaining tissue distribution and clearance kinetic parameters from lungs and other tissues indicate that at least three sampling times, including PEO-1 (immediately after exposure), PEO-2- and PEO-3, and 4–5 animals per sampling point is recommended ,12,13,141/2) and elimination rate. Soluble nanomaterials such as AgNP have been known to follow a two-compartment model of fast and slow dissolution rates [Most insoluble nanomaterials are eliminated from the lung by first-order elimination kinetics ,14,15. Ton rates ,14. For We understand that the current toxicokinetic TG 417 explicitly states that the test guideline is not intended for the testing of nanomaterials , the TG If we follow the revised OECD inhalation toxicity test guidelines, more test animals are required. Specifically, TG 412 and 413 require lung clearance of solid particles and the BALF assay to objectively evaluate lung toxicity. Following the guidelines, 60–80 more animals are needed, as we demonstrate. Based on our laboratory’s work, we demonstrate that nanomaterials are uniformly deposited in multiple lobes in the lung burden. The remaining right lung lobes can be used for BALF analysis. The left lung can be used for histopathological evaluation. We see this as an opportunity to reduce animal use for OECD inhalation studies.