Purpose: Frameworks can be influential tools for advancing health and equity, guiding population health researchers and practitioners. We reviewed frameworks with graphic representations that address the drivers of both health and equity. Our purpose was to summarize and discuss graphic representations of population health and equity and their implications for research and practice.Methods: We identified publicly available frameworks that were scholarly or practice oriented and met defined inclusion and exclusion criteria. The identified frameworks were then described and coded based on their primary area of focus, key elements included, and drivers of health and equity specified.Results: The variation in purpose, concepts, drivers, underlying theory or scholarly evidence, and accompanying measures was highlighted. Graphic representations developed over the last 20 years exhibited some consistency in the drivers of health; however, there has been little uniformity in depicting the drivers of equity, disparities or interplay among the determinants of health, or transparency in underlying theories of change.Conclusion: We found that current tools do not offer consistency or conceptual clarity on what shapes health and equity. Some variation is expected as it is difficult for any framework to be all things to all people. However, keeping in mind the importance of audience and purpose, the field of population health research and practice should work toward greater clarity on the drivers of health and equity to better guide critical analysis, narrative development, and strategic actions needed to address structural and systemic issues perpetuating health inequities. Graphic representations, such as conceptual frameworks, are often used to help clarify and distill a set of concepts that are fundamental and their relationship to a phenomenon. Conceptual frameworks are particularly important when a single theory, theoretical framework, or perspective is deemed insufficient to capture a complex phenomenon. In research, conceptual frameworks shape the epistemological paradigm—or belief systems for how and why we know the world—brought to the phenomena of interest. Conceptual frameworks can help guide the framing of research projects, how relevant questions are determined, how meaning is attached to data, and the resulting development of research findings. Similarly, in practice, such frameworks can help shape how people consider and approach the identification and prioritization of problems to be addressed, identify and interpret relevant data and research findings, and implement and evaluate solutions. Such frameworks, therefore, have the potential to affect how we collectively understand, investigate, and address societal and community issues.In the early 1990s, two broad conceptual frameworks for considering the factors that influence health were published.3Population health is one such complex phenomenon for which both researchers and practitioners have developed and graphically represented frameworks. The graphic representations of these frameworks show a broad picture of health and its drivers that go beyond simply defining health as the absence of disease and health care as the primary driver of health. A collection of these frameworks, representing a continuously expanding set of determinants that influence health, was reviewed in 2015 by the Canadian Council on Social Determinants of Health (CCSDH).4 noted, scholars have offered multiple definitions of health equity over the years. For the purposes of this review, we follow Whitehead's 1992 definition: “Equity in health implies that ideally everyone should have a fair opportunity to attain their full health potential and, more pragmatically, that none should be disadvantaged from achieving this potential.”5 More recently, new frameworks and associated graphic representations of health have emerged that do attempt to incorporate drivers of equity in the context of health, such as the World Health Organization's (WHO's) Commission on the Social Determinants of Health (CSDH) conceptual framework6 and the Bay Area Regional Health Inequity Initiative (BARHII).7 We find such frameworks to be important to a field that increasingly prioritizes examination of the distribution of determinants and, subsequently, health outcomes across communities. We therefore set out to review such frameworks.Many of the frameworks in the CCSDH review do not, however, specifically address the factors that influence how determinants of health and their related health outcomes are distributed within and across communities (or populations). We define such factors that shape the distribution of determinants and, subsequently, health outcomes as drivers of equity. As McCartney et al.8 In addition, it is not designed as a formal evaluation of the frameworks reviewed. Rather, the purpose of this review is to stimulate discussion on how frameworks (describing relevant concepts and their relationships for study of a topic9) or models  shape understanding of knowledge and principles used in population health research and practice and how we collectively understand the drivers of health and equity in our work.Similar in approach to the CCSDH review, this essay discusses graphic representations of frameworks of drivers of health and equity. It differs from the CCSDH review in that it centers inclusion criteria on the drivers of equity . Given the focus on graphic representations, it does not review an exhaustive catalog of frameworks used to explain drivers of health, nor does it include frameworks that represent drivers of equity outside a health context. Our emphasis on the drivers of health and equity is also different from another Canadian review by the National Coordinating Center for Determinants of Health, which focused on knowledge to action models.Our approach for this work went beyond what is normally applied for a traditional narrative review , particularly around inclusion/exclusion criteria, which are seldom reported for narrative reviews. Our approach also differed from other systematic and narrative reviews in that we were searching for graphical depictions rather than original research studies. So, to identify existing frameworks that address the drivers of health and equity, our initial search strategy involved using Google, PubMed, and Google Scholar from March 2019 to January 2020 for English-language documents and images based on the following keywords:  AND  AND (frameworks OR models OR theories). We followed up with snowball sampling from citations of documents found and searches of relevant organizational websites, reports, and gray literature were also reviewed. We conducted a broad, but not exhaustive, search for frameworks that were published in the 21st century when materials became more widely available on the internet. We did not focus our search on formal research databases because we were particularly interested in finding images of frameworks that have been used in practice.11–14Must mention equity or like terms : for example, several well-known or emerging frameworks do not mention equity or like terms.15 did not include a graphic at the time of retrieval.Must include a graphical depiction of the drivers of health equity: for example, Braveman has written extensively about health equity, but we were unable to find a conceptual framework in her work. Similarly, the new Well-being in the Nation Measures16 only lists general drivers of equity .Must include specific drivers of health equity : for example, Chang17 provides a comprehensive listing of determinants (or drivers) of health equity, but does not show how they relate to equity, health, or each other.Must include arrows, nesting, sequencing, or other graphical approaches to show drivers' relationships to equity: for example, King County's 14 Determinants of Health Equity18 is specific to environmental health disparities.Must address general health/equity, not specific topics such as drivers of asthma, behavioral medicine, and gender equity: for example, Gee and Payne-Sturges's framework8Must focus on frameworks addressing drivers of health/equity rather than frameworks focused on actions to improve health/equity: for example, the frameworks reviewed by Davison et al.From these materials, we selected frameworks for review that were scholarly or practice oriented and met the following inclusion criteria:4 and BARHII7 frameworks. Inclusion criteria were developed collaboratively among the authors, based on disciplinary and practical knowledge. Results are expected to inform discussion in the field on what shapes health and equity, how it is graphically portrayed, and the implications for our research and practice.Frameworks were excluded from the sample if they were not posted on the internet or if they represented derivatives of included frameworks. For example, several organizations have published modified versions of the WHO CSDHOnce we had selected frameworks to be included in our review, one co-author extracted information directly from applicable articles or websites and another co-author checked the extraction to be sure we accurately recorded information about the frameworks. Following discussions with all the authors that led to the development of a list of key background information and elements, we then conducted a qualitative review of the frameworks with two co-authors coding information independently and then reconciling differences in interpretation of frameworks and background information. The lead author served as the final arbiter for any difference not reconciled. Our intent was to be sure that we reported shared, rather than individual, interpretations of information reflected in the frameworks. We coded the following information:Primary area of focus:○ Community practice ○ Policy development , and/or○ Research.Key elements:What is in the framework:1.3)Role of individuals and communities in driving health and equity .How do things relate:4.3)Shows interactions between determinants Salience, credibility, and legitimacy:6.Based on peer-reviewed literature 7.3)Recognition of importance of upstream action  were published in 2015 than in any other year. Sixteen of the frameworks (59%) were developed in the United States, with the remaining frameworks coming from Australia, Canada, and Europe. Eight of the frameworks were published in peer-reviewed literature with the remaining 19 (70%) coming from gray literature. More than half of the frameworks were published by government entities . Eight of the frameworks were either developed by the WHO's Commission on Social Determinants or were influenced by their work; and of these, all but one was developed outside the United States. While few of the framework descriptions clearly articulated their underlying theories, the theories mentioned in the WHO work included ecosocial, psychosocial, and social production of disease/political economy of health. Other theories mentioned included fundamental causation and life course. Principles of social justice and human rights were also mentioned in a minority of the framework descriptions.Two-thirds of the frameworks were framed positively, that is, their outcomes were stated in terms of well-being or equity. Outcomes in the remaining one-third of the frameworks were framed negatively, comprising terms such as inequity or disparity.We found that at least 22 (or 81%) frameworks drew from peer-reviewed literature—this was the most common key element identified among the frameworks. The next most frequent key element was the inclusion of some metrics, which we found for 17 (63%) of the frameworks. Examples of metrics include measures such as age-adjusted mortality rates, percent of population under the federal poverty level, and the Gini coefficient as an income inequality metric. Beyond acknowledging that there are inequities in health outcomes, over half of the frameworks also recognized the existence of inequities in determinants or policies  or highlighted the importance of upstream action . Just over half of frameworks reviewed acknowledged multiple disparity domains , such as among racial/ethnic groups, socioeconomic status, or by age groups.The least frequently classified key elements were highlighting the roles of individuals and communities (found in only 37% of frameworks), interaction between determinants (37%), and identifying fundamental causes of inequity (33%).19 which includes all the key elements, except for mentioning multiple disparity domains, and the Public Health Agency of Canada's,20 which includes all elements, except for showing interactions between the determinants of health and equity. Three frameworks include all but two key elements: Centers for Disease Control and Prevention's Promoting Health Equity21 , the WHO CSDH frameworks6 , and Victorian Health Promotion Foundation's framework22 .Frameworks developed to serve as a guide to future research are likely to be subject to different criteria than frameworks designed to guide community practice. Thus, given the different purposes of the frameworks, it is not surprising that no single framework included all the key elements. The frameworks with the most key elements was Schulz and Northridge's,23 and the National Institute of Minority Health and Health Disparities24 frameworks, which were both based on peer-reviewed literature, and the Colorado Department of Public Health framework,25 which included some metrics.Three frameworks included only one of the key elements we identified: the Winnipeg Regional Health AuthorityIn In The most frequent subcategories identified were environment-social, political, and cultural , community assets and environment—built or natural , and individual experience, identity, and social position .12 Frameworks are also intended to organize thinking and shape narratives, which in turn shape the boundaries of what is possible for action. And frameworks can also be used to help raise awareness and make sense of the issues that shape health and equity.We believe that frameworks can serve many purposes: they can inform research agendas, planning and decision making, or assessment. Frameworks can be considered boundary-spanning tools to engage new audiences among disciplines, sectors, or community groups. For example, the County Health Rankings measurement framework has helped advance conversation about the social determinants of health.We found many more frameworks than the 27 frameworks that met our criteria. The low number was both a reflection of our search approach and the stringency of our selection criteria. Several published frameworks that we found, but did not include, are derivatives of other frameworks and, as such, did not meet our inclusion criteria for review.In terms of purpose, the focus of frameworks that we found from outside the United States was more likely to be on policy development. And, of the key elements, the non-United States frameworks were more likely to mention multiple disparity domains and recognize inequities in determinants and policies. However, the real benefit of including frameworks from outside the United States was the additional richness provided by the types of drivers of health and equity that they included.Only eight of the frameworks were published in peer-reviewed publications and research was the stated purpose of most of these frameworks, that is, none of the eight were intended to guide community practice. However, we were heartened to see that many of the frameworks intended to guide community practice found in the gray literature were based on peer-reviewed literature. The linkage between scholarly work and practice continues to be important.26 For those positively framed, it is also unclear how to deal with historical policy and practice that underlie inequity, such as assimilation laws aimed at Native Americans and Jim Crow laws. Furthermore, some (positively or negatively framed) frameworks illustrate what should be measured, while others only illustrate what can currently be measured. For example, several frameworks include constructs that should be measured, such as civic engagement or political factors, whereas, in reality, what can be measured may be limited to metrics such as voter participation.Recent dialogue about equity in the field of population health has focused on the importance of an asset-oriented approach, or positive framing. Asset-oriented approaches serve to counter the negative default assumptions about communities that bear disproportionate burden of inequitable conditions. However, it is not clear whether this approach is more likely to change the way equity is studied or practiced. Most of the frameworks reviewed were positively framed, none provided comprehensive metrics that quantify assets that influence health or measurement of equitable outcomes—a recognized current limitation in the field.Given that equity is a comparative principle, or judgment about how a person or group of people is situated relative to others, it is intriguing that very few, if any, frameworks were explicit about underlying theories, values, and norms that provide context for sense making of what is avoidable, unfair, and unjust. The absence of clear guidance about whether and how conditions are unjustly produced, raises questions about utility for deriving innovative scholarship or practice.As the field embraces intersectionality, frameworks will also need to evolve to acknowledge interactions among determinants and interconnections of multiple disparity domains. Few frameworks effectively did so among those we reviewed. While identifying many of the known relationships and interactions between components of a framework is important to guide future research, showing all such relationships in a framework intended to guide community practice can be confusing, sometimes described as arrow soup. Conversely, failing to show important interactions can lead to misunderstanding at the least, or far worse, could lead decision-makers, practitioners, or communities to overinvest or underinvest in resources in the most impactful or intertwined factors that could improve health and equity.27 who proposed four essential features for a fundamental social cause of health inequalities:One potential way to focus attention on the most important interactions is to identify fundamental or root causes of health and equity, sometimes referred to as the “causes of the causes” or “upstream of the upstream.” Fundamental cause theory was developed by Link and Phelan1.It influences multiple disease outcomes, meaning that it is not limited to only one or a few diseases or health problems.2.It affects these disease outcomes through multiple risk factors.3.It involves access to resources that can be used to avoid risks or to minimize the consequences of disease once it occurs.4.The association between a fundamental cause and health is reproduced over time by the replacement of intervening mechanisms.29They believed that the reason for such persistent associations, and the essential feature of fundamental social causes, was that they involve access to resources that can be used to avoid risks or to minimize the consequences of disease once it occurs. They defined resources broadly to include money, knowledge, power, prestige, and beneficial social connections . They have since suggested that there may be additional “fundamental causes” that include freedom, racism, discrimination, and stigma.Our examination of current frameworks for health and equity included in this study revealed several commonalities in the conceptual elements, such as community conditions and context, which have been increasingly understood as the social determinants of health. Interestingly, there was more variation in conceptual elements that extended health determinants into the realm of equity determinants. For example, only five frameworks included political or institutional power as drivers of health and equity and only two explicitly mentioned prejudice and stigma.27 Phelan and Link,28 and Hatzenbuehler et al.,29 other potential candidates identified from these frameworks include political, governance, and economic context; legal norms; and societal values. Several of the frameworks also added more specificity to the concept of power, including political and institutional power.As noted above, nine of the frameworks identified some drivers as “fundamental” or “root” causes of health inequity. In addition to the fundamental causes suggested by Link and Phelan,1 the America's Health Rankings,13 and the County Health Rankings,12 were included because they include no explicit acknowledgment of equity. As Krieger30 pointed out, the determinants of health and the determinants of health inequalities are not necessarily the same. She argued for visual models that “clearly and unequivocally delineate the social facts of skewed distributions of power and resources and depict the societal processes that generate and maintain these distributions and their embodiment in population levels and distributions of health, disease, and well-being” (p. 1103).Notably, neither classic nor familiar models of the social determinants of health, such as Evans and Stoddart,28 are not consistently incorporated into our population health and equity frameworks has implications for our practice and research, and ultimately for our progress on persistent and in some cases growing health inequities. The variation across frameworks implies that the field of population health research and practice has yet to reach consensus on the determinants of health and equity and signals a nascent health equity field.The fact that causes identified as fundamental more than two decades agoThere are formative questions regarding the variation in and relationships among conceptual elements that could help the field move closer to consensus. To name a few, Are there additional criteria for fundamental causes beyond those offered in fundamental cause theory? Or criteria that distinguish determinants of health from determinants of equity? If health behaviors illustrate individual choices based on the opportunities we have, how does this fit into health and equity frameworks? And how can we measure complex overarching concepts, such as culture or power?6 or BARHII7) that we had already found. Specifically, although the image search proved helpful in locating additional frameworks, it captured many complete or partial duplicates. Other weaknesses of not having done a fully systematic search and review include a potentially biased selection of frameworks with a bias from the potential to omit, oversimplifying the content of frameworks, and the fact that for qualitative reviews, there is far more debate about what methods and approaches are appropriate.31As noted in the introduction, this analysis does not represent an exhaustive catalog of frameworks and models of the drivers of health and equity nor is it designed as a formal evaluation of them. It also does not meet the strict criteria for a systematic review, for example, we did not record every framework that was derived from other frameworks . Instead, our interest in this review was primarily on the content of the graphical depictions in terms of the types of drivers of health and equity that are presented.and the distribution of health within communities. We believe that this is a necessary step for the field of population health as we strive to be more equity focused and before identifying types of policies, systems changes, practices, and other actions that might improve health and equity outcomes. The range of action-oriented frameworks not captured in this analysis is also important and future work will be needed to minimize disconnects between driver-oriented and action-oriented frameworks.This review was conducted as part of an effort to develop a broader framework that reflects the drivers of health Frameworks can be influential tools for advancing health and equity. However, the frameworks we examined were not consistent in their inclusion of the potential categories or dimensions of drivers of health and equity. As a result, they do not offer conceptual clarity on what shapes health and equity for the field of population health. This article highlights the variation in purposes, concepts, drivers, underlying theory or scholarly evidence, and accompanying measures put forth in current health and equity frameworks. Some variation is expected as it is difficult for any framework to be all things to all people. However, keeping in mind the importance of audience and purpose, the field of population health research and practice can work toward greater conceptual clarity on the drivers of health and equity. While numerous graphic representations of population health and equity exist, further work to visually represent underlying theories that drive value-based assessment of equity needs focused attention if we are to collectively advance our efforts for health and equity.


Mortality data obtained from the Mortality Information System identified a total of 19,499 deaths in women caused by corpus uteri cancer in Brazil. However, the association between mortality and sociodemographic factors in these women is not fully understood. A study based on the secondary data on deaths caused by corpus uteri cancer recorded in the SIM-DATASUS was conducted. Deaths reported from 1996 to 2016 in the health information system were included. Sociodemographic factors were analysed to determine their association with mortality. Low schooling is highly associated with mortality in all administrative regions. Advanced age, race and marital status have specific association with mortality for the different geographic regions. Black, Brown and Indigenous women with low schooling and of advanced age are highly associated with mortality. Brown, White and Black women of advanced age had the highest corpus uteri cancer related mortality rates. Women with low schooling who died of corpus uteri cancer were either single or widows. The marital status of Black, White and Brown women aged <59 years was single. The sociodemographic factors that predict mortality in women with corpus uteri cancer in Brazil were presented and can be used to guide public health. Tumours of the corpus uteri are divided into the following two main groups: endometrial tumours and mesenchymal tumours. The former are common gynaecological diseases, whereas the latter manifest more aggressively and are rarer with worse prognosis than the former. Endometrioid adenocarcinomas and carcinosarcomas or leiomyosarcomas, considering clear types of tumours alone, are the most common types of endometrial tumours and mesenchymal tumours, respectively .The proportion of adenocarcinomas accounts for greater than 80% of all corpus uteri cancers in all countries studied, except in Brazil (74.1%). In Brazil, the proportion of unspecified morphology is comparatively high (13.1%), and the proportion of sarcoma is low and is approximately 1.2%–5.1% of all corpus uteri cancers [Approximately, 95% of uterine malignancies are endometrial carcinoma . WorldwiThe onset of corpus utreri cancer is usually in postmenopausal women. Its occurrence and mortality are highly associated with overweight and obese women . AdditioMortality data obtained from the Mortality Information System (SIM) of the Brazilian Ministry of Health, available on the DATASUS website with annual data collected from 1996 to 2016, identified a total of 19,499 deaths of women caused by corpus uteri cancer in Brazil .This study aimed to analyse the sociodemographic factors that predict mortality in corpus uteri cancer in Brazil. Specifically, the sociodemographic factors  will be evaluated to determine their association with mortality from 1996 to 2016.This study analyses secondary data available in the DATASUS. The data are publicised with unrestricted use and access. Ethical assessment of the research ethics committee is not required according to the terms of the National Health Council Resolution No. 466 of December 12, 2012.An analytic, descriptive and retrospective study based on secondary data on deaths caused by corpus uteri cancer recorded in the SIM of the Ministry of Health of Brazil was conducted.The SIM is a secondary database available in the Informatics Department of the Brazilian National Health System (DATASUS) of the Ministry of Health . Deaths Geographic regions, age, marital status, race/ethnicity and educational attainment were considered the sociodemographic factors. These factors were further categorised as follows: geographic regions , race/ethnicity , age , marital status  and schooling (no schooling greater than 12 years).p < 0.05. We obtained these estimable parameters by the APC Web Tool  [The data were submitted for descriptive and inferential analysis. For the description of data, absolute and relative frequencies were used. Age-period-cohort (APC) analysis using a suitable model that accounts for the identification problem to discern variations in mortality due to independent effects of age groups, calendar time periods of death and birth cohorts was performed. For all analysed variables in this study, the following functions have been estimated: net drift ; local drifts ; all age deviations ; all period deviations ; all cohorts deviations ; and all period (or cohort) rate ratios (RR) (age incidence pattern in every period (or cohort)). Wald test was used to verify difference significative, being considered MD, USA) . The chiThe highest number of deaths from uterine cancer was observed in women with the following characteristics: aged 60 to 79 years (59.02%), belonging to the White race (61.44%), with low education ≤3 (31.58%), married (34.84%) or widowed (33.54%) and reside in the Midwest (56.33%) of Brazil. The results are shown in The results obtained in the analysis of the APC are seen in The association between administrative regions and race, age group, schooling and marital status is presented in According to the sociodemographic factors, the association between geographic region and race and mortality was as follows: White women from the South and Southeast regions, Black and Yellow women from the Southeast region, and Brown women from the North, Northeast, and Midwest regions had six times higher chance of mortality than those from the rest of the regions. Indigenous women from the Midwest region were highly associated with mortality, with five times higher chance of mortality compared to those from the rest of the regions.Hence, an association between women’s’ geographic region and age and mortality caused by corpus uteri cancer was observed, and from these data it was, women aged <19 years in the Northeast region; women aged 50–59 years in the North, Northern and Midwest regions; and women aged 60–69, 70–79 and greater than 80 years in the Southeast region were highly associated with mortality.Regarding the level of schooling, women from the North, Northeast, and Midwest regions with no schooling, women from the South and Southeast regions with 1–7 years of experience in schooling, and women from the Southeast region with 8–11 years and ≥12 years of experience in schooling were highly associated with mortality caused by corpus uteri cancer. However, women who presently study  or had advanced schooling (South region) exhibited lower odds of mortality. Interestingly, there were lower odds of mortality in the Southeast region.According to the data on the marital status of women, single and married women from the North and the Northeast regions, married and widowed women from the South region, widowed and divorced women from the Southeast region and married and divorced women from the Midwest region were highly associated with mortality caused by corpus uteri cancer.The association between race and age group and mortality caused by corpus uteri cancer is presented in White and Yellow women with high education and Black, Brown and Indigenous women with low education were highly associated with mortality. White women with low education and Black with high educational level had lower odds of mortality. Indigenous women with high education and Yellow women with low education had no association with mortality. Women aged ≤69 years with high level of education and women aged ≥70 years with low level of education were highly associated with mortality.The association between marital status, race, age group and schooling and mortality caused by corpus uteri cancer is presented in The association between age group and mortality caused by corpus uteri cancer was as follows: single women aged <59 years were highly associated with mortality, and women aged <19 years had 59 times higher chance of mortality. Married and divorced women aged 40–69 years were highly associated with mortality. Moreover, widowed women aged ≥70 years were associated with mortality, with women aged greater than 80 years having five times higher chance of mortality.Additionally, White and single and married women exhibited lower odds of mortality, while widowed and divorced women were positively associated with mortality. Moreover, Black and Brown single women were highly associated with mortality.Corpus uteri cancer is a very common gynaecological malignancy, especially in high-income countries. Although the overall prognosis is relatively good, high-grade corpus uteri cancer tends to recur. Recurrence needs to be prevented since the prognosis for cancer recurrence is worse than the initial cancer. This study analysed the sociodemographic factors that predict mortality caused by corpus uteri cancer in Brazil . SpecifiThe results of APC analysis revealed that mortality is higher with increasing age. Black women aged 60–69 years, Yellow women aged 50–59 years, and Brown women aged 20–69 years were highly associated with mortality, with results showing that higher chance of mortality was noted even in younger women. The association between elderly women and mortality caused by corpus uteri cancer is well understood in the literature, showing a higher risk mortality in elderly women in relation to younger women .According to a study using the data from Brazil, Black women presented a higher percentage of corpus uteri cancer progression or recurrence compared to non-Black women, and all of these women benefited from the public health services offered, a common characteristic that makes this group homogeneous .Cancer health differences are often described as the unequal burden of cancer deaths in one racial/ethnic group compared to another. For example, the National Cancer Statistics in the USA shows that death from 9 out of the top 10 cancers in men and women is mostly observed in Blacks. Considering that there is no association between genetic and biological variances for these differences, it is possible to associate these results with the unequal distribution of the social determinants of health as the primary cause of cancer differences .It was confirmed that Black, Brown and Indigenous women with low schooling have a greater association with mortality and White and Yellow women with a high level of schooling. It can be hypothesised that the low schooling group has greater difficulty in accessing healthcare services compared to the other groups. Low educational levels can lead to low health literacy; hence, women with high educational level are able to access, understand, and act on complex health information and communicate with healthcare personnel . HoweverAccording to the presented results on marital status, there is a lower association between mortality and married women compared to other marital statuses, supporting other studies , 18 thatIt was observed that in the North and Northeast regions, mortality was higher in Brown women aged less than 60 years, with emphasis on the association in Indigenous women living in the Midwest region. These women have difficulty accessing the health policies in the country, mainly due to geographical and cultural barriers .These results are possibly associated with women in these regions having higher difficulty accessing the oncological treatment centres compared to the South and Southeast regions, where the highest number of mortality is observed in women aged greater than 60 years . The strThe results of the analysis support the initial hypothesis that the interval between cancer diagnosis and early treatment is longer for women with vulnerable social characteristics, regardless of the stage of the disease, compared to women with no vulnerable social characteristics. There is a clear consensus in the literature that the shorter the interval between diagnosis and treatment, the better the prognosis and patient survival. Immediate action is essential to the effectiveness of treatment in more advanced stages of the disease or patient comfort in palliative treatment .Understanding the association between sociodemographic factors and mortality caused by corpus uteri cancer is essential for the development of public policies worldwide, but in Brazil, similar to other developing countries, it is necessary to recognise that there are limitations on the quality of data collection. A very high number of unknown or unreported data that greatly undermine the reliability of the analysis performed in studies using secondary banks are noted. On the contrary, the number of unknown data has declined over the years. Another limitation is characterised by the change of terms and items in the collection worksheets, reducing the standardisation in the collection and data releases in the platform .In this study, we found that the sociodemographic factors of race, age, schooling, marital status and geographic regions present specific characteristics that predict mortality in women with corpus uteri cancer in Brazil. These findings can be used to review or develop new public health guidelines and policies. Thus, there is a need to improve the existing public policies to prevent death caused by corpus uteri cancer, especially for the most vulnerable population with less social support and greater difficulty in accessing oncological healthcare services.The authors have no conflicts of interest to disclose.The authors participated in all the stages of the study.No funding was received for this work.


To help older adults begin or adhere to regular physical exercise, several studies have endeavored to identify barriers to active behavior. However, there is a lack of information about barriers for active older people. In addition, most of the reviews of the literature compare only active people to inactive or sedentary people without examining in detail the barriers with respect to the degree of commitment to behavioral change. Finally, there is no consistency in the results of studies investigating the effects of barriers on the relationship between stages of change and exercise behavior. The first aim of this narrative review is to compare barriers that affect exercise stages of change from those that affect levels of exercise behavior in a healthy older population and the factors that can lead to relapse or dropout; the second aim is to identify the extent to which barriers hinder the relationships between stages of change and exercise behaviors. The results showed that barriers are well identified in sedentary people and in the first two stages of change (pre-contemplation and contemplation) compared to active seniors and other stages of change . Consistency between the formulations of the different stages in comparison with the transtheoretical model and the definition of barriers and the limitations of measuring physical activity in the different studies are discussed. Finally, novel perspectives of research are proposed to address the flaws in the reviewed studies. The World Health Organization recommends that more attention be paid to increasing levels of physical activity . These rResearchers have used numerous theoretical models to understand the determinants of physical exercise ,18,19. AIn order to write our narrative review, the PubMed, Web of Science and PsycINFO databases were searched (last search on June 2020) using the following keywords: (barrier) combined with (elderly OR older OR aging OR senior) AND  AND (“stages of change” OR “readiness of change”). Following this search, duplicate references have been removed. Then, the titles and abstracts of the retrieved papers were screened for relevance. Studies were included if they were written in English and if they reported barriers to physical activity in subjects aged >50 years old. When the sample included a larger age range, the article was included if data concerning the target ages were available. Papers were excluded if they examined palliative, frail or cognitively impaired patients. Studies aiming primarily to identify barriers to physical activity in older adults were excluded because several reviews of the literature already examined these studies ,14,28,29Perceived barriers belong to the decisional balance concept, which is a measure of attitude that captures how individuals weigh the consequences of a specific behavior in terms of pros and cons ,34. ApplAccording to Marcus and Forsyth, people in precontemplation are not engaged in exercise and are not thinking about starting an exercise program . Those iAs already reported, the terms physical activity and exercise are frequently used interchangeably. Exercise is defined as a subtype of physical activity, specifically, “planned, structured, repetitive, and purposive bodily movement done to improve or maintain one or more components of physical fitness”  or as “aOur results highlight two main categories of studies. The first category concerns studies that have explored the relationship between barriers and exercise behavior. The second category includes studies that have explored the relationship between barriers and stages of change. Only studies with tangible results concerning energy expenditure, stages of change and barriers have been reported in the tables.Two questions are asked in this section. First, how are perceived barriers and physical activity and exercise measured? Second, what barriers are reported by sedentary and active people? By examining perceived barriers questionnaires, three formulations can be identified: (1) measures that assess barriers that prevent older adults from exercising ,42; (2) By examining studies aimed at considering the relationships between barriers and level of physical activity, the majority of them reported lack of time, lack of interest, fear of injury or bad health conditions as barriers to regular physical activity for sedentary people ,54. In cTo sum up, this section highlights two interesting conflicting findings. First, some studies have shown that regardless of the level of engagement in physical activity, the barriers remain the same. However, older people who are active or have already been active will be more sensitive to environmental  barriers than people who never have been active. This point deserves further examination. Second, the number of obstacles to participation in physical activity requires further studies, as a single barrier may be enough to disengage someone from physical activity . No need to accumulate barriers to stay inactive.In this section, two concerns are addressed: (1) measures of perceived barriers and stages of change and (2) barriers cited in the pre-action and post-action stages. The measures of barriers suggested by the TTM are applied in three out of five studies ,70,71. HIn the same manner as in the previous section, barriers are relatively well identified with sedentary people  but not in later stages. For older people in precontemplation and contemplation stages, a lack of time (too busy), being too tired and bad health are most often cited as barriers ,72. HoweIn summary, the first two sections that discussed the relationship between barriers and exercise behavior and stages of change show that while there are links that are established, the results are not generalizable due to several methodological differences. These differences include the use of different definitions of the perception of the barrier when measuring it in different studies, the use of different tools to measure physical activity levels and the lack of consensus in the preparation stage.Eight studies were identified that examined the relationship between barriers, exercise behavior and exercise-related stage of change. Five of the eight studies are based in part on TTM, and three are not theory-based. The measurement of perceived barriers is somewhat confusing going from unidimensional measure  to a scoDo these findings question the relevance of the transtheoretical model among a healthy elderly population? Before questioning the consistency of the model with older healthy people, let us return for a moment to the results. Why is the hypothesis difficult to explore? Based on this review, four explanations can be reported: the lack of a clear definition of each stage of change and, more specifically, the contemplation and preparation stage; the definition and formulation of perceived barriers; the measurement of physical activity; and the distinction between barriers that hinder the transition between each stage of change from those that hinder the increase in the level of physical activity.The definitions of perceived barriers make the examination of the results complex for the two following reasons. First, the definition does not always fit with the theoretical model. Second, the formulation of the items is not always in concordance with the definition. For instance, in King and colleagues’ study, the authors asked older people to rate whether the following conditions  were present in the participant’s neighborhood . This quAmong the eight studies ,72,73,75One of the findings of our narrative review is that almost all of the studies used self-reported questionnaires to measure physical activity levels. However, the literature shows that self-reported questionnaires have three limitations . The fir−1·kg−1. These barriers are, in order of importance, poor health, lack of time, lack of motivation, tiredness and environmental barriers . In contrast, the results are less obvious when people are either insufficiently or sufficiently active. A lack of time is the most commonly reported barrier in studies [It appears that some barriers are the same when older people are sedentary, that is, in pre-action stages of change (PC and C) or at levels of activity under 1.5 kcal·day studies ,64,71,72 studies ,72. Exce studies .In brief, TTM studies are generally based on social-cognitive theory, which considers health behavior change as a continuous process and assumes that the theory’s factors are relevant for all individuals. As suggested by Schüz et al. , the ideA first limit of our work was that four of the studies ,41,45,72This review highlights the barriers reported by older people in different stages of behavior change. Helping people overcome barriers to physical activity is an intervention that successfully guides physical activity programs, but identifying these barriers before engaging in physical activity could help avoid adherence failures and attrition. In addition, this work shows that barriers correlate with exercise behavior and stages of change in the majority of studies that have been reviewed on this topic but rarely predict exercise behavior change. However, future studies need to consider standardizing the items used to measure the stages of change and the definition of barriers. It also seems essential that in future studies, diversification of the measurement of physical activity should be avoided. From this perspective, it would be interesting to standardize the measurement of physical activity levels by completing subjective measures with objective measures in future research programs aimed at clearly establishing the relationships between barriers, stages of change and exercise behaviors.


Emerging and re-emerging infectious diseases and zoonoses indicate the importance of the One Health (OH) approach for early warning. At present, even when surveillance data are available, they are infrequently timeously shared between the health sectors. In the context of the MediLabSecure (MLS) Project, we investigated the collection of a set of surveillance indicators able to provide data for the implementation of integrated early warning systems in the 22 MLS countries of the Mediterranean, Black Sea and Sahel regions. We used an online questionnaire , focusing on seven relevant arboviruses, that was submitted to 110 officially appointed experts. Results showed that West Nile virus was perceived as the most relevant zoonotic pathogen, while Dengue virus was the most relevant non-zoonotic pathogen in the study area. Data collection of early warning indicators is in place at a different level for all the investigated pathogens and in almost all the MLS Countries. Further assessments on the reliability of the collection in place and on the feasibility of piloting an integrated early warning system for arbovirus could verify if integrated early warning really represents the Achilles’ heel of OH. The One Health (OH) concept is gathering greater attention over the last decades due to the (re)emergence of human pathogens from animal reservoirs and the outcomes of studies on the impact of environmental and climate changes on the transmission of several infectious diseases ,2,3,4. OThe OH approach is promising in terms of surveillance and control of vector-borne diseases (VBDs) because it makes use of trans-disciplinary cooperation at the human–animal–ecosystem interfaces ,9. AmongWith limitations, integrated surveillance  systemsIn fact, the identification of early warning indicators in association with rapid implementation of prevention and control measures could reduce the severity of arbovirus epidemics ,19. Ad hTo tackle this, a number of studies have already been performed to predict the risk of VBDs transmission using climate data ,23,24,25This subject is crucial in the networking project named MediLabSecure (MLS), which involves 22 non-EU countries of the Mediterranean, Black Sea, and Sahel regions . The netTo this aim, we identified a set of surveillance indicators that could assist in increasing regional early-warning capacity and verified, through a survey, their collection at the national level.The study focused on emerging and re-emerging arboviruses  representing possible priorities for the various geographical areas included in MLS network. Moreover, general interest to these pathogens was confirmed in late 2018 during a OH scientific conference held in Rome  and a OHFrom January 2019, using scientific references ,26,37 anIn order to gather local information about the utilization of potential indicators in the countries of the MLS network, we developed an online questionnaire using Google Form©. A draft form of the questionnaire was piloted by a small group of external experts who assessed appropriateness of wording, comprehensibility, clarity of the instructions, and time needed to complete the questionnaire.We implemented the questionnaire in three versions , harbouring common features and sector-specific questions for each pathogen see . At the In May 2019, the three versions of the online questionnaire were submitted to 110 officially appointed contact points of the 22 countries of the MLS network. The version focusing on vectors was sent to entomologists, that on human indicators to human virologists and human public health professionals, and that on animal indicators to animal virologists and veterinary services professionals. Several reminders were sent out for completion from June to July, and answers were collected until September 2019. Information collected through the survey administration app was then compiled and analyzed using MS Excel 2016©.The indicators selected among those identified from the literature are reported in Vectors  were investigated in terms of presence, abundance/density, seasonality, and infection rate.For humans, two general indicators (population density and population age distribution), and three pathogen-specific indicators regarding disease frequency or occurrence were considered.The animal-related version of the questionnaire investigated only three zoonotic pathogens: CCHFV, RVFV, and WNV. Questions regarding the collection of two general indicators were asked . Furthermore, the pathogen-specific indicators were animal disease occurrence and animal disease seroprevalence.Overall, 21 of the 22 MLS network countries responded with at least one completed questionnaire. Countries’ responsiveness was higher in the entomology sector (20/22), followed by the animal (30/44) and human sectors (28/44). In some of the MLS countries, the public health sector is divided on a regional basis, therefore in two cases more than one questionnaire was completed for the same sector. As a result, a total number of 81 questionnaires were collected and analyzed: 20 from entomologists, 31 from animal virologists and the official veterinary sector, and 30 from human virologists and the public health sector. Zoonotic pathogens  were investigated in 81 questionnaires, while 50 questionnaires concerned non-zoonotic pathogens .From the questionnaire responses, WNV was perceived as the most relevant zoonotic pathogen in the study area, followed by CCHFV and RVFV. Specifically, WNV was relevant for 73% (59/81) of respondents, CCHFV for 63% (51/81), and RVFV for 49% (40/81) . Among tIn line with the aim of implementing early detection strategies in the MLS network area, the regional relevance of the selected pathogens was analyzed . To accoWithin the regionally grouped data, WNV was the most relevant pathogen for the respondents from Balkans and North Africa; for Black Sea region CCHFV was the most important; in Middle East region DENV was considered relevant, whereas all respondents from the Sahel region considered RVFV as the most important.To investigate the surveillance systems in place in each sector for the different pathogens, questions about which indicators are routinely collected were asked. The most frequently collected indicator in the entomology sector is “vector presence,” regardless of the involved pathogen, while data on “vector infection rate” are rarely gathered .The results from the human sector questionnaires show that population density and population age distribution data are collected in almost all cases . To evalData on animal population are collected in 100% of the cases for cattle, goats, and sheep, and to a lesser extent for equids and camels; these data are rarely collected for wild species. Data on animal movements and trade are frequently collected in terms of import and export, and quite often for pastoralism and transhumance practices. Wild animal information (wildlife migrations) is again gathered very rarely. Data regarding disease occurrence and disease seroprevalence in animals are collected to a different extent depending on the pathogen considered .A. aegypti and A. albopictus) and more than half of these areas are reporting cases of Zika, Dengue fever, Chikungunya, Yellow fever, and/or Rift Valley fever.As stated by Leta et al. , arbovirThe pathogens’ relevance perceived by the respondents of our survey is in accordance with their diffusion in the region. WNV is the most widely distributed arbovirus on the planet ; RVFV isAccording to the information gathered by our survey, the collection of indicators suitable for early warning is in place with a range of different situations in the MLS network countries. At this stage, it would be possible, albeit challenging, to identify opportunities for targeting disease threats upstream  in order to support the reduction of occurrence and impact of arboviruses transmission .From the questionnaire results, vector presence predictably resulted as the most collected vector indicator. On the contrary, vector infection rate was the most difficult to gather in case of mosquitos-transmitted pathogens, while for CCHFV (transmitted by ticks) the least collected indicator is vector abundance/density. Therefore, vector species-specific differences should be taken into consideration when interpreting these results. This said, a limitation of the present study is the use of the same indicators regardless of the vector species involved . Moreover, different people and/or different laboratories of the same institution may focus on specific vector species ; as a result, addressing our questionnaire to only one of them may have limited the collection of information or biased the results. However, in order to mitigate this risk, we strongly recommended our contact points to share the questionnaire with relevant colleagues when appropriate. Information on vector seasonality is instead less available, although by analyzing the collection of this indicator by country and by pathogen, coherent explanations might be found . Nevertheless, lack of awareness on the importance of some indicators for the monitoring of certain pathogens could also explain their unsuccessful collection.Data on disease frequency or occurrence in humans (both either suspected cases or lab confirmed) is collected by the majority of the countries involved. On the other hand, less effort is dedicated to seroprevalence studies, despite their potential importance in areas where the disease has been not reported yet.Interestingly, information on animal population density is collected in all the involved countries for some domestic species, supplying national authorities with important data for animal disease surveillance. However, information regarding wildlife is rarely gathered: surveillance programs in wildlife are needed and desirable, not only in order to investigate the health status of wildlife populations, but also to investigate on potential reservoir of infection and, therefore, to prevent the spillover in animals and humans .A final section in all the questionnaires allowed for the collection of information on indicators relevant to climate and environment . The preliminary analysis of this information shows that this collection should be strengthened, especially in light of the increasing environmental and climate impact on the diffusion of arboviruses.Collecting data through an online questionnaire proved to be the most convenient and effective solution to quickly gather information from the MLS region. However, this method has some disadvantages: it was not possible to verify the quality  of data collection in place, nor to investigate individual special cases discovered with the study.Having assessed that each of the sectors involved in the surveillance was collecting indicators for the most relevant arboviral infections in the MLS region, the next step is to verify if a specific selection of appropriate indicators amongst those presently collected can provide the ability to predict or allow for early warning, especially in terms of a One Health perspective (“integrated early warning”).The piloting of such a type of integrated approach could help to understand if integrated early warning represents the Achilles’ heel of OH, until more effort will be put into setting up all the requirements needed to operationalize such a system. Among others, the need to increase the performance of the system is crucial in terms of sensibility and specificity through the integration of data from different sources and Institutions. This is only possible with the presence of shared or closely connected information systems, procedures, and indicators.A certain grade of collection of surveillance data (indicators) is already in place in the MLS region. Their collection should be strengthened and the gaps on critical indicators addressed .It appears now worthwhile proceeding with further assessments which can help clarify the reliability of the indicators collected and the feasibility of the implementation of an integrated early warning system for arboviral infections. Since some relevant indicators are already being collected, this would not demand for extra resources but, on the contrary, its operationalization could lead to savings. Deep studies in promising countries could help to address the problem and would represent the chance to pilot integrated early warning systems using data already being collected and to promote the collection of critical data not yet gathered.As stated by Berthe et al.: “One Health is a sound management approach, fully aligned with the definition of ‘health,’ and good practice for its predicament on the use of increasingly scarce resources, therefore improving efficiency and efficacy” . Let us


The BioRescue project is an international enterprise using ARTs to save the northern white rhinoceros from extinction. The situation of the northern white rhinoceros is particularly critical as there are only two individuals of this subspecies still alive and they are both infertile females. The application of the ETHAS to the procedures contributed to the overall acceptability of the project and improved communication among the project’s partners. In turn, the tool itself was also refined through an iterative consultation process between experts (both ethicists and scientists) and stakeholders.Applying assisted reproductive technologies (ARTs) to the conservation of endangered species may be the only way to save them from extinction. However, ART application can raise relevant ethical issues and could benefit from a comprehensive ethical assessment. Unfortunately, there is a lack of attention to the topic in the scientific literature and, to our knowledge, there is no tool for the ethical assessment of ARTs in the context of conservation that has been described. In the present paper, we show the effects of applying a dedicated ethical self-assessment tool, the Ethical Assessment Tool (ETHAS), to ovum pick-up and in vitro fertilization procedures performed within the BCeratotherium simum cottoni) conservation project. The ETHAS consists of two checklists, the Ethical Evaluation Sheet and the Ethical Risk Assessment, and is specifically customized for each ART procedure. It provides an integrated, multilevel and standardized self-assessment of the procedure under scrutiny, generating an ethical acceptability ranking  and a risk rank , and, hence, allows for implementing measures to address or manage issues beforehand. The application of the ETHAS to the procedures performed on the northern white rhinoceros was effective in ensuring a high standard of procedures, contributing to the acceptability and improved communication among the project’s partners. In turn, the tool itself was also refined through an iterative consultation process between experts and stakeholders.Assisted reproductive technologies (ARTs) can make a difference in biodiversity conservation. Their application, however, can create risks and raise ethical issues that need addressing. Unfortunately, there is a lack of attention to the topic in the scientific literature and, to our knowledge, there is no tool for the ethical assessment of ARTs in the context of conservation that has been described. This paper reports the first applications of the Ethical Assessment Tool (ETHAS) to trans-rectal ovum pick-up (OPU) and in vitro fertilization (IVF) procedures used in a northern white rhinoceros ( In the present global scenario, where an accelerated rate of extinction is paired with a severe decline in populations’ abundance in surviving species ,2, assisARTs, in fact, may offer the only chance for survival of many endangered species with very fragmented populations or only few extant individuals. In this case, ARTs can be employed not only to boost the number of offspring, but also to enhance the genetic exchange between the fragmented populations (living both in situ and ex situ) without the need of actually translocating the animals , ARTs caWhile ARTs are a robust opportunity in the conservationist’s toolbox—and one which promises to become increasingly important in the future—their application may raise several ethical issues. The use of ARTs can raise ethical concerns also in human medicine, some of which can be still valid when ARTs are applied to non-human animals, but many of the issues raised by the application of these technologies in conservation breeding projects are more specific ,10,11. TAbove all, a crucial source of ethical concern regarding ARTs in biodiversity conservation is animal welfare. Many applications of ARTs require manipulation of live animals and, in some case, invasive procedures, with real risks for their welfare. This is of course also true for farm animals, where the issue has not received enough attention , butIn general, when an ethical assessment of a procedure involving individual animals has to be carried out, the golden standard would be a systematic project evaluation, requiring, among other things: (i) a risk assessment; (ii) an assessment of welfare conditions and pain, suffering, distress, and lasting harm imposed on the animals; (iii) a harm–benefit evaluation; and (iv) the application of the 3Rs  . This stRisk assessment, for instance, should be considered essential in these cases. Application of ARTs to wildlife and their biomaterial entails accepting a certain grade of uncertainty. This requires a prior definition of the ethically tolerable risk threshold for the procedures, which can be conducted only by performing a detailed risk analysis, based on traditional risk analysis , specifiThe assessment of potential pain, suffering, distress, and harm, alongside general welfare conditions of the individual animals involved in the procedure, should also be considered essential. However, pain, suffering, distress, harm, and, in general, the welfare of the individual animals have traditionally played a secondary role in biodiversity conservation. This is partly due to the fact that the goals of biodiversity conservation and of animal welfare are conceptually distinct and may sometimes diverge, since the former is mainly focused on species, whereas the latter is focused on individuals ,30,31. NThe third important requirement is harm–benefit analysis. Again, while this is nowadays routine in the ethical assessment of laboratory projects involving animals , it is iThe same can be said also for the fourth requirement, the application of the 3Rs, which has been widely satisfied in laboratory research but rarely in wildlife studies, where research conditions are more heterogeneous and it is harder to standardize a methodology for its implementation as has been done in laboratory research. However, as progressively stated ,40, the It may be countered that conservation interventions do not qualify—at least in a full sense—as research and, as such, should not be subjected to the same stringent standards involved in laboratory research. However, as already noted, the boundaries between research and veterinary practice are often blurred when applying ARTs to conservation breeding programs. Moreover, most applications of ARTs to wildlife may take place both in research and non-research scenarios. This raises a boundary problem, as the same activity may be subjected to different ethical standards of evaluation when performed in different contexts. To solve this inconsistency, it has been suggested that far from relaxing our ethical standards on research, we should instead extend them to all similar activities ,42.https://www.scopus.com/), with “ethical assessment” AND “reproduction” and “wild” and “animal” as keywords run in December 2020, gave no results. One of the reasons for this result could be that, with ARTs being applied to conservation breeding projects often in the gray area between clinical practice and research, their use in such context often does not require external ethical approval. It is therefore even more important that the practitioners and the researchers involved in these types of projects are able to evaluate the potential ethical relevant issues spanning from the procedures they use themselves. One way to enable practitioners and researchers to evaluate their procedures is to provide them with a comprehensive and customizable tool for the self-assessment of such procedures, which, once developed by experts with an ethics background , can be used also by people lacking such background. Self-assessment could also be an important step in preparation for an external overall evaluation of the ethical acceptability of a project and could help scientists to be proactive and to scrutinize the ethical issues surrounding their work [For all these reasons, conservation projects incorporating ARTs should be carefully scrutinized in order to evaluate their ethical acceptability, using the highest procedural standards and compliance with best practices and regulations as landmarks. Currently, despite the increasing interest in the use of ARTs in conservation, there is little attention to ethical assessment and, to our knowledge, there are no tools to evaluate the specific risks and ethical aspects involved. A simple search on Scopus (eir work .Ceratotherium simum cottoni—NWR). The procedures involved both southern white rhinoceros (SWR) females in European zoos and the last two surviving NWRs. The assessment was preformed using a self-assessment tool explicitly designed for conservation breeding programs, the Ethical Assessment Tool (ETHAS), as customized for the self-assessment of ovum pick-up (OPU) and in vitro fertilization (IVF) procedures. The aim of the study was to investigate both whether applying the tool could contribute to ensuring a high standard and improvement of procedures being assessed and, at the same time, how applying the first version of the tool in actual field conditions contributes to shape and improve the tool itself.In this paper, we present the self-ethical assessment of two ART procedures performed in the context of a conservation breeding program aimed at avoiding the extinction of the northern white rhinoceros (Ceratotherium simum), once ranged over much of the savannah of Central Africa [Ceratotherium simum simum—SWR). In order to produce embryos, however, gametes have to be obtained first. During the last two decades, scientists have collected the semen from four NWR bulls and cryopreserved it in three different cryobanks [The NWR, a subspecies of the white rhinoceros  and comprising the Czech Dvůr Králové Zoo, Avantea laboratory, Max Delbrück Center for Molecular Medicine (MDC), Kyushu University and Padua University , which is in charge of the whole project that involves Najin and Fatu and aims at avoiding the final extinction of the northern white rhinoceros.Given the complexity of the ethically relevant issues involved, a sub-project dedicated to the development of a specific ethical self-assessment tool which could be used in mammalian conservation breeding programs was created within the BThe Ethical Assessment Tool (ETHAS) is a flexible and customizable instrument for the ethical self-evaluation of specific ART procedures applied to mammals in biodiversity conservation projects. It includes and integrates with each other risk assessment , pain/distress/welfare evaluation, harm–benefit analysis and the 3Rs tenet application. As already stated, self-assessment tools help scientists to be proactive and to scrutinize the ethical issues surrounding their work and are preliminary for an external overall evaluation of the ethical acceptability of a project . Their iETHAS is based on checklists, a tool commonly used in medicine and other fields to identify errors, ameliorate operational standards and comply with best practices ,59. ChecETHAS’s checklists aim to combine risk assessment with ethical acceptability assessment. Risk assessment is a crucial phase of risk analysis, and therefore it is very important for the overall ethical acceptability of wildlife conservation projects. As it is known, risk analysis is a three-step process: (i) risk evaluation/assessment, (ii) risk management and (iii) risk communication ,61. It aTherefore, the general frame of the ETHAS tool is based on two integrated checklists for self-assessment, the Ethical Evaluation Sheet (EES) and the Ethical Risk Assessment (ERA). Each ERA item is conceptually linked to a corresponding part of the EES checklist, which comprises, among others, all the relevant ethical aspects that are investigated in ERA. The link is reported in a column with an alphanumeric code.There are customized EES and ERA versions for each ART procedure, but all share some common features. These constituent checklists of both EES and ERA have been developed on the basis of the current literature and best practices guidelines and refined through an iterative consultation process between experts (both ethicists and scientists) and stakeholders, which is still ongoing in the present stage of the project. They merge risk analysis, based on a combination of traditional, animal welfare and specific ethical risk assessments, with ethical analysis, based on pain/distress/welfare evaluation, harm–benefit analysis and the 3Rs tenet application, with the aim of defining the overall ethical acceptability of the procedure under assessment.The Ethical Evaluation Sheet (EES) highlights potential ethical issues arising from the ART application. As with corresponding tools for the ethical assessment of research projects with laboratory animals ,64,65,66ioRescue team with an ethical background in applied ethics in conservation and animal welfare. However, as underlined in the Introduction, in the final version of the tool, any member of the team performing the procedures will be able to fill in the EES, without the need of a specific ethical background. During the EES compilation, it is asked to answer “yes” or “no” to all items, depending on whether the requirements are met or not. Moreover, for some EES items, it is required to add further information to explain the answer. The EES is evaluated using a semi-quantitative scoring model in which the answers “yes” or “no” assume the value of 0 and 1, respectively. The sum of the items’ outcome divided into three homogeneous ranges defines the rank of the ethical acceptability of the procedure: not acceptable, partially acceptable, acceptable. Therefore, the final score obtained from the EES compilation identifies one of the three acceptability ranks. The EES is designed to be filled in only once (unless the procedure’s protocol is changed) before to start the procedures. In the case of the procedures performed during the present study, as it was a phase in the development of the final version of the tool, the EES was filled in by a member of the BThe identified acceptability level that represents the outcome of the EES assessment (defined as the first review level) defines the degree of the procedure acceptability. In case of a partial or not acceptable result in the ethical assessment, detected with the first review level, each section of the EES checklist is assessed individually. This second review level identifies at which section of the procedure corrective actions need to be planned. Finally, a third review level allows identifying the items whose requirement is not met and, therefore, the critical issues of the procedure to be reviewed before the procedure begins.The ERA checklist is specifically customized for each procedure under scrutiny by identifying the appropriate phases for risk assessment. The scientific literature on ARTs has been revised to analyze, in detail, each step of the OPU and IVF procedures and detect possible hazards and ethical risks whose occurrence could negatively impact on the animal welfare, staff safety and procedure outcome . As showThe IVF-lab ERA, instead, as shown in Each item and sub-item of the ERA checklists analyzes an element of the procedural step which could cause a hazard to the success of the phase under assessment. For each item, it is required to record a “yes” or “no” whether the requirement of the item is satisfied or not. Depending on the characteristics of the requirement and on the severity of the consequences associated with the hazard scenario, each item is scored differently . For exap) and consequences (x) associated with the occurrence of a hazard scenario [The assessment uses a semi-quantitative scoring model where the risk is determined by a single value R that combines the probabilities  or not (no/no answer) and ix is from 1 to 3, as described in In the specific model, n corresponds to the number of scenarios chosen to describe the risk (number of items of the ERA checklist), ioRescue project, the local veterinarian and the managing director of the facility where the procedure took place.ERA checklists are designed to be filled in each time a procedure is performed. They have to be filled in by one to three different people, depending on the procedure under assessment, with two main aims: to have an overview of the procedure and to verify, in case of more persons involved in the assessment, if communication regarding ethically relevant issues among the participants is effective. Regarding the OPU procedure, for instance, if it is executed only by the veterinary staff of the zoo or facility hosting the animals, the ERA can be filled in just by the chief veterinarian. If the OPU procedure is executed by an external veterinary team, the ERA has to be filled in both by the external and internal veterinarians and the zoo or facility managing director. In the applications of the ETHAS described in the present paper, three different participants responded to the OPU ERA for both the procedures performed: the veterinarian responsible for the BRegarding the second aim—to verify if communication is effective—the three answers for each item are entered in an Excel spreadsheet, and the modal value that allows highlighting the most frequent responses per set of answers is calculated. The sum of the modal values is divided into three ranges, identifying the three categories of risk severity . On the contrary, the modal value is not necessary at all for the IVF-lab ERA because it is compiled by only one person—the person responsible for the IVF laboratory. In this case, the sum of the values of each answer is divided into three ranges, corresponding to the three risk categories .Similarly to the EES, also for the ERA, three review levels can be applied: at an overall level , at the phase level (second review level) and at the items level (third review level). The review levels allow revising the specific application of the procedure in case of the detection of a medium or high risk rank and applying risk management and risk communication strategies.The ETHAS generates a risk rank  through the ERA and an ethical acceptability rank  with the EES. The overall final evaluation (ERA + EES) is calculated by combining the acceptability ranking obtained from the EES and the risk rank obtained the from ERA . Therefo(1) Acceptable, when the ESS results in totally acceptable and the ERA detects low risks. The assessed procedure may be accepted without further actions.(2) Acceptable with mitigation, when the EES results in partially acceptable and the ERA detects medium risks. The assessed procedure may be accepted only if critical issues are identified and addressed and the specific application of the procedure is revised.(3) Not acceptable, when the EES detects a not acceptable result and the ERA detects high risks. The assessed procedure may be unacceptable until further improvements are enforced to eliminate the associated ethical concerns and procedural risks.Scoring of both checklists and the overall final evaluation have to be performed by the person completing the EES.After the risk assessment, the ETHAS enables risk management of the possible highlighted hazards. Risk management  allows raising awareness of the potential hazards and risks and enables the sharing and acceptance of the measures to be adopted to reduce the risks. Risk mitigation actions have to be chosen taking into account: (1) the characteristics of the requirements (in terms of scoring); and (2) what is reasonable and technically possible. Moreover, risk management allows an exchange of information and opinions between the staff involved in the ART procedures.Finally, the ETHAS enables also risk communication: through an iterative process among the staff directly involved in the procedures, information and opinions on hazards and their associated risks are exchanged, allowing a transparent and overarching discussion of results.ioRescue project both for approaching their infertility problems and for protocol optimization—and those (August 2019) performed on Najin and Fatu, in order to ensure suitable consideration of the relevant specific features of these individuals  in the tool. The IVF procedures witnessed were all performed at the Avantea laboratory, which up to now is the only one that produced a viable rhinoceros embryo.In a preliminary phase of ETHAS development, after consulting the relevant scientific literature and best practice guidelines on OPU and IVF procedures, a draft of the checklists was designed using a bottom-up approach, by witnessing several procedures and discussing with the teams performing them the main areas identified by the scientific literature and best practices. Relevant areas, not previously found in the literature search, but found to be relevant in the practical application of the ART procedures, were also added and discussed. The OPU procedures witnessed in the preliminary phase included both procedures performed on infertile SWRs in European zoos—who were involved in the BioRescue team on three sub-fertile or infertile SWR females housed in a European zoo, in order to evaluate both the effects of conducting ethical self-assessment on the application of ART procedures and to improve the beta version of the tool itself.The preliminary phase led to the first version (beta1) of the ETHAS customization for OPU procedures (OPU EES + OPU ERA). The complete beta1 version can be found as ioRescue team on the last two NWRs in Kenya. Both procedures (October and December) were performed following the BioRescue team’s standardized protocols. Similarly, the first version (beta1) of the ETHAS customization for IVF procedures (IVF-lab EES + IVF-lab ERA) was first applied in August 2019 , pain/distress/welfare evaluation, harm–benefit analysis and the 3Rs tenet more likely had the potential to make the assessment and, eventually, help in the detection of problematic issues than using only one of these approaches separately. If we analyze, in more depth, the results of the ETHAS assessment, the harm–benefit analysis part allowed highlighting both positive effects and harms that could be generated by the execution of the OPU and IVF-lab procedures on wild animals and their specimens. Among positive effects highlighted during the assessment were: routine health and welfare check-up of the animals involved; the possibility of propagation of the genetic material of the specimens involved; scientific knowledge and know-how improvements that might find positive applications in other fields; the development of new technologies and procedures to promote the health and welfare of wild animals; the development of protocols for the conservation of endangered wild species. It was also possible to check whether the Bandscape ,114. TheThe local staff was also directly involved in the compilation of the OPU ERA, since a general and comprehensive goal of the ETHAS is to facilitate discussion among participants. The testing of the ETHAS confirmed that the tool was effective in this respect. As the results of the OPU ERA checklists showed, after the first application, the issues with negative answers caused by a lack of communication were not detected in the second one. In general, better communication among participants helps to avoid, reduce or manage the risks of the procedures and to guarantee high standards. The application of the ETHAS to the laboratory procedures contributed to guarantee high standards also in the IVF procedure and to safeguard the biomaterial involved, as the three embryos created by NWRs are of exceptionally high conservation value.Through the ETHAS, it was also possible to check for potential harms that may occur during the procedures and if everything possible was done to avoid their occurrence. The main potential harms highlighted by ETHAS application mostly concern the possible side effects of the veterinary procedures on the animals’ health and welfare, correct preservation of the biomaterial and staff safety. However, since potential risks might occur during the veterinary procedures on wild animals, ETHAS application allowed highlighting the above-mentioned critical points, investigating whether action plans have been developed to deal with them and facilitating discussion around them between the staff members.With regard to the animal welfare issues involved in the procedure, as highlighted by the positive results of the items specifically designed in the OPU ERA and EES, it was found that the team was committed to preserve and protect animal welfare, by monitoring the animals before, during and after the procedures, through physiological and behavioral analyses. Moreover, even if scientific evidence shows that the OPU procedure can be repeated on the same animal several times, the ETHAS allowed for checking if an adequate time-lapse between procedures was respected, as dictated by the best veterinary practices. Furthermore, specific items of the ERA checklist were included in order to analyze the welfare of other animals not directly involved in the procedures, such as herd mates sharing the same facilities or even enclosures.Implementation of the 3Rs was another purpose of the ETHAS. Results showed that refinement, reduction and replacement were applied in the procedures whenever possible. For instance, refinement was applied by developing a new instrument for oocytes pick-up in rhinoceroses and by improving the procedures and techniques, with the aim of increasing the welfare of the animals involved, the efficacy of the procedures and the correct preservation of specimens. Another aspect related to refinement was the inclusion of items regarding environmentally friendly waste disposal in the EES, after the first trial. The replacement of laboratory media with synthetic ones, the replacement of materials with lower environmental impact and the replacement of procedures and equipment with a lower impact on animal welfare were considered and applied whenever possible. Finally, reduction was implemented by maximizing the number of sampling procedures under the same anesthesia to reduce the number of veterinary interventions as much as possible.Furthermore, the applications of the ETHAS in different conditions (zoos and semi-captive management) have contributed to refine the accuracy and inclusiveness of the tool itself. OPU and IVF-lab ERAs underwent several applications that allowed improving the tool via a shared work between ethicists and experts. This process permitted reviewing and refining the checklists iteratively through a participative approach.Last, but not least, a general and comprehensive goal of the ETHAS was to assist scientists to carry out a self-assessment in addressing ethical evaluation of ART application in conservation projects. The results of the present study show that the application of such an ongoing assessment was effective in ensuring the high standards of the procedures, including respect for animal welfare, and facilitating effective communication among participants. It is important to note that the application of a form of ethical self-assessment to procedures or projects constitutes in itself a contribution to their acceptability even if no problematic issue is detected. All this is a value in itself and can increase acceptance of this kind of project by the public.Limitations and Future DevelopmentsSelf-assessment can also be seen as the main limit of ETHAS application, as the evaluation process can be interpreted as self-referential. Nevertheless, as already pointed out, the primary function of ethical self-assessment is to help scientists think, in detail and proactively, through ethical issues surrounding their research. Usually, ethical evaluation regarding conservation projects, when it is performed, is made by an external authority, which gives a general ethical approval to the overall project before it starts. On the contrary, ethical self-assessment offers the opportunity for an ongoing detailed scrutiny of all the main ethical aspects involved in the project, including the procedures that are carried out on animals, being proactive in detecting hazards for their welfare and taking measures to minimize them beforehand. In general, ethical self-assessment allows for a comprehensive and transparent evaluation process which can also be communicated to the public.Another difficulty in applying such tool is the balancing between the need for standardization and that for customizing procedures and situations. Moreover, the fact that the tool is designed to evolve through iterative confrontation makes standardization more difficult. Notwithstanding, the ETHAS will continuously be tested in different contexts, species and procedures, in order to increase the comprehensiveness of the tool. However, it is important to note that the general frame and most of the tool are already adaptable to a more general use in different contexts, species and procedures, such as semen collection, embryo transfer, surrogate pregnancy and birth management, and to other innovative procedures regarding stem cell-associated techniques.ioRescue project, which, alongside the development and testing of new approaches in the conservation of a “technically extinct” species, implemented a self-assessment tool designed for improving the procedures from an ethical standpoint. The application of such a tool within the project allowed for the mutual goals of improving some aspects of the communication among the projects’ partners and improving the tool itself, to be applied in the near future to other contexts in which ARTs are applied for the conservation of other mammal species. Despite the obvious advantages of this kind of self-assessment, such an approach is almost underestimated in the literature dealing with ART in conservation, as shown by a simple Scopus search on the subject. Therefore, tools such as the ETHAS could raise the ethical standards of applications of ARTs to conservation and, in this way, contribute to their success.Ethical assessment of the application of ARTs in conservation is important for many reasons. In conservation breeding programs, for instance, animal welfare is a crucial element to be considered, alongside safety for the people involved and the quality of the procedures. Moreover, ethical assessment—especially when performed in the guise of self-assessment—allows anticipating the critical aspects that can compromise the ethical acceptability of a procedure and intervening before their eventual occurrence could damage the reputation of the whole conservation project and alienate societal support. As ARTs will become ever more important for conservation, the need to expand and deepen the ethical research on this topic will increase. An exemplary case, in this sense, is provided by the B