General Data Protection Regulation. One of the mechanisms established by this new law to strengthen the individual’s control over their data is the so-called “right to be forgotten”, the right to obtain from the controller the erasure of records. In gender transition, this right represents a powerful form of control over personal data, especially health data that may reveal a gender with which they do not identify and reject. Therefore, it is pertinent to discern whether the right to have personal data deleted—in particular, health data—is ethically acceptable in gender transition. Towards addressing the ethical dimensions of the right to be forgotten in this case, this study presents relevant concepts, briefly outlines history, ethics and law of records considering the evolution from paper to electronic format, the main aspects of identity construction and gender identity, and explores the relationship between privacy, data protection/information control and identity projection. Also, it discusses in gender transition the relation between “the right to self-determination”, “the right to delete”, and “the right to identity and individuality”. Conclusions on the ethical admissibility of the ‘right to be forgotten’ to control gender-affirming information are presented.The European Union (EU) faced high risks from personal data proliferation to individuals’ privacy. Legislation has emerged that seeks to articulate all interests at stake, balancing the need for data flow from EU countries with protecting personal data: the  Cambridge Analytica during the 2016 USA presidential election campaign to influence undecided voters for the benefit of candidate Donald Trump is an example of this problem [General Data Protection Regulation (GDPR) [confidential treatment requests, including end of life plans, where people ask to be allowed to die at home or enter instructions such as “do not resuscitate” [It is undeniable that the European Union (EU)’s adoption of new legislation concerning personal data protection comes from a technological evolution that has generated a massive collection, conservation, and proliferation of data over the past two decades , 69, 82. problem . Consequn (GDPR) . One of n (GDPR) , 56. ForIn gender transition, the right to be forgotten represents a powerful form of control for the owner over personal data, especially health data that may reveal a gender with which they do not identify and reject. Therefore, it is pertinent to discern whether the right to delete personal data—in particular, health data—is ethically acceptable in gender transition.At this point, it bears emphasising the complexities of transition because it can take the form of legal, social, and medical, or often some combination of two or three. For instance, some trans people use hormones and change their legal sex but do not have any surgeries. Also, some studies address said complexity mainly because there is scientific evidence of the relationship between stigma and health care vulnerability of transgender and gender-nonconforming people , 84, 86.Towards addressing this issue, we will start by defining relevant concepts. Briefly, outline history, ethics and law of records considering the evolution from paper to electronic format, the main aspects of identity construction and gender identity and expression, and explore the relationship between privacy, data protection/information control and identity projection. Also, we will analyse in gender transition the relation between the rights to “self-determination”, “delete”, and “identity and individuality”. We present conclusions on the ethical admissibility of the right to delete to control gender-affirming health information.personal data relating to the inherited or acquired genetic characteristics of a natural person which give unique information about the physiology or the health of that natural person and which result, in particular, from an analysis of a biological sample from the natural person in question”—Article 4/13 GDPR [“Genetic data”—“/13 GDPR ;personal data related to the physical or mental health of a natural person, including the provision of health care services, which reveal information about his or her health status”—Article 4/15 GDPR [“Health data” or “Data concerning health”—“/15 GDPR ;“Right not to know”—right for individuals not to be informed/acknowledged of personal information ;right for individuals to have personal data erased” [“Right to be forgotten”—“ erased” ;A person’s biological status  as male or female. An individual's sex at birth (birth-assigned sex) is usually determined based on genital appearance, with those present usually assuming that other components of sex are consistent with the newborn’s genital sex.” [“Sex”—“al sex.” A person who has a gender identity that corresponds with the gender assigned at birth.” [“Cisgender person”—“ birth.” The attitudes, feelings, and behaviours linked to one's biological sex's experience and expression.” [“Gender”—“ession.” refers to each person's deeply felt internal and individual experience of gender, which may or may not correspond with the sex assigned at birth, including the personal sense of the body  and other expressions of gender, including dress, speech and mannerisms.” [“Gender identity”—“erisms.” , 85The expression of one's gender identity, often through appearance and mode of dress, and also sometimes through behaviour and interests. Gender stereotypes often influence gender expression.” [“Gender expression”—“ession.” refers to the social process of being recognised or affirmed in one's gender identity, expression, and/or role. Although gender affirmation can be theorised as an inherently social process, it must necessarily also be conceptualised as multidimensional with at least four core constructs: social , psychological , medical , and legal . There is no one single path to gender affirmation—no "one size fits all" approach describes how trans people affirm their felt or expressed gender. Some trans individuals pursue social but not medical gender affirmation; some pursue medical but not legal gender affirmation, and so on. Gender affirmation sometimes, but not always, conforms to binary categories of being female or male. Furthermore, gender affirmation does not require linearly following a discrete series of “transition” events—it is conceptualised as an ongoing process throughout the life course.” [“Gender transition” or “Gender affirmation”—“course.” People who have a gender identity that is different from the gender assigned at birth. This includes people who might or might not undergo gender reassignment, as well as those who prefer or choose to present themselves differently from the expectations of the gender assigned to them at birth.” [“Transgender and gender-nonconforming people (trans or gender minority)”—“ birth.” .Birth is a fact of autonomous relevance, regardless of motherhood and fatherhood. It is essential even if it is impossible to identify the mother and the father, as is the registries of abandoned children. However, in history, this has not always been the case. Indeed, as Andrade  points oOn the other hand, according to Durbach , the hisNowadays, registration has become the first step for the state to secure all forms of citizenship, that is, to ensure that they are acknowledged to benefit from the distribution of social state resources, i.e. to ensure that they are protected by society. Registration allows access to widespread personal and economic development tools such as getting a job or a passport. Indeed, besides identity construction, there are other practical reasons for registering one’s identity. For example, people are interested in registering themselves correctly to receive corresponding identity documents necessary for voting or board an aircraft. Undoubtedly, these are some of the reasons for promoting birth registration as a relevant UNICEF activity in the world .Thus, in contemporary society, facts that have an essential impact on relationships with others, such as birth, parentage, marital status, parental responsibilities, nationality, and gender, are recorded in a mandatory manner. Registration allows safeguarding values and principles of certainty and security as to the effects of the people involved. When registered by the state, these data are compulsory, so there is an obligation to register. Thus, registration has a double role: it is an organisational measure of the state; and is regarded as a means of personal affirmation or self-determination, since individualisation through registration facilitates respect for human dignity. Identity registries represent the person’s affirmation as a unique human being, assisting respect for each individual's human dignity. It should also be acknowledged that identity registries serve other functions, such as surveillance and policing. For instance, allegedly, the REAL ID registration system in the United States has anti-terrorism purposes .Furthermore, given the technological revolution of the last two decades, the state has advanced with registering and archiving personal identification data and health and genetic information. The ease of dissemination and connection of data has increased the need for health and genetic data protection, raising complex ethical and legal issues in gender transition, which we will discuss onwards.Gender identity substantially relates to human dignity since it plays a vital role in identity construction. Although the right to delete may cover registered realities other than gender, namely, challenges to paternity or maternity established at birth or adoption, gender identity—a personality-related fundamental value—represents an independent scope for ethical analysis given its complexity.Human beings are usually divided in a binary way, either female or male, based on biological information commonly exemplified and recorded at birth . Usuallyimperfect exercise” since the documented results revealed insufficient long-term functional and psychological effects of an early approach. Therefore, this perspective suggests the maintenance of the “male genital phenotype, visibly not corrected in girls, which, however, is inadmissible for most parents.” [sexual identity and peer-group identification is important.” [A significant number of countries continue to address gender through a dualistic classification of biological sex. A pathology-based conception of trans and nonbinary identities still exists, which justifies studies to find the best solutions for altered conditions in genital appearance detected at birth. Thus, the pathology-based literature on this subject addresses the advantages and disadvantages of early surgery. Thomas  found tharents.” . Also, oarents.”  argue thortant.” . We agreAt this point, it should be acknowledged that the pathology-based approach has been subject to substantial critique because the establishment of gender does not depend on physical characteristics but identity. Gender expression is another concept related to gender identity, and a person’s gender expression may, or may not, follow their gender identity . For exaThe comprehensive notion of gender nowadays still encompasses difficulties in choosing sex for registration under different conditions of the morphological sex of the newborn. There is a risk of being arbitrary, and the registered individual may link to a gender with which they might not identify. Besides, problems to transition it later might happen, according to the jurisdictions of the various countries. This difficulty has led to the suggestion that birth registries should admit a third approach, such as a simple procedure for subsequent alteration, or that reference to sex should be omitted. The United Kingdom discussed this idea on a similar issue in 1947. Attempts to allow birth certificate without the father’s name had limited success but were made as a public health measure and in light of the high mortality rates of out of wedlock children . RecentlStill, in some European countries , although gender markers are in use, it is unnecessary to undergo gender-affirming surgery for gender transition legal recognition. Gender identity is based on self-determination , 53, so The concept of privacy is not consensual, but we believe it is an expression of human dignity. We will try to demonstrate this point by confronting arguments from relevant literature. Whitman , for exaFor don’t we assume that there must be a right not to be watched in certain situations and that we should be able to control other peoples’ access to personal information to some degree? The idea that privacy entails being in control of personal information about oneself again links privacy to autonomy, but in this perspective, autonomy is a precondition of dignity.”Despite the outstanding writing style Whitman  uses to However, in an era of perpetual technological evolution, we are continually facing new instruments, such as combining the physical domain with the virtual one, the so-called “Internet of Things” (IoT).strictu sensu) to protect the facts themselves, which are primarily innocuous but, once interconnected, convey the individual’s essence without himself knowing it [Furthermore, the means of collecting, preserving and analysing personal information has increased exponentially , since towing it . TechnolAt this point, it bears emphasising that ethics and law view rights differently, although they are correlated. Ethics corresponds to a reflection by the society of a mandatory directive’s choice for its members. That is, it concerns an axiological selection of the behaviours desired by a particular human group. The human being is allowed a wide variety of options in the sphere of personal decision, which we call self-determination. However, individual choices result from internal traits, the environment, and interactions with society, resulting in subjective opinions. Thus, it is necessary to find a minimum neutral standard accepted by the conscience of any individual. These standards of conduct taken by any human being, regardless of their ideological or religious principles, constitute the values that shape ethics. The law, in turn, assesses human conduct being permeable to the facts, as it values them in the construction of its norms. However, the law often brings rules and principles impregnated with ethical values, recognised by the political system as essential to its formation. In this way, legal regimes have moral foundations, such as the dignity of the human person.Notwithstanding, the right to data protection guarantees an individual the right to dispose of all data relating to his personality, health, personal life, political or religious conviction, race, for example. Thus, it serves to sustain privacy protection in a world where collecting, storing, and intersecting large amounts of data is possible , 50, 74.Representing a more robust form of personal data protection, the right to be forgotten has recently emerged. The literature on this subject approaches this new law and its ethical foundation from managerial, legal, and societal perspectives , 69, 70.As enshrined in European culture and legislation, the right to be forgotten raises interesting ethical questions because it does not limit deleting data of any kind. Patients appear to have the right to exclude their health information if the data are no longer required for reference by the purpose for which it was collected or processed, or even if consent is withdrawn. Besides, it seems this right exists when the data subject opposes processing, and there are no legitimate grounds for rejecting this request; also, when the data has been processed unlawfully—all these reasons following Article 17 of the GDPR . The lawIn another approach, the right to identity and individuality is considered a fundamental human right. It may take varied ethical contours, namely, the subjects’ right to be informed about their biological ancestry. Amzat and Grandi  point ouNonetheless, if data exist, even if private and only accessible under limited circumstances, the importance of not knowing can be compromised by unwanted revelations of information . Given tUniversal Declaration of Human Rights [All human beings are born free and equal in dignity and rights”.In this way, some arguments contribute to the admissibility of the right to forget or delete health and genetic data related to gender transition: those we have already mentioned and the ideas that support transgender rights. As emphasised by Powell et al. , these rn Rights , “All huNonetheless, when discussing transgender rights as human rights, it is crucial to stress the proportionality principle that is a cornerstone concerning the international human rights system. Indeed, the principle of proportionality consists in assessing the suitability, necessity and balance of state intervention in a specific fundamental right. It is based on moderation and justice logic that should apply to any state intervention in individuals’ rights, even if the restrictive act’s purpose is to avoid harm to another individual right .The only purpose for which power can be rightfully exercised over any member of a civilised community, against his will, is to prevent harm to others. His own good, either physical or moral, is not a sufficient warrant.” [The societies that developed after World War-II under the guidance of the abovementioned international instrument sought to translate, through its principles, a plural understanding, encompassing individuals with diverse ethical expectations and different visions of the world. Pluralism of thinking in modern societies leads political systems to respect freedom. That is, citizens have the right to live their lives in the way they understand, being limited only by others’ rights. In this sense, public authorities should only intervene in their citizens’ free choices to avoid harming other individuals . This idarrant.” . In othearrant.” . In Millarrant.” Similarly, as long as the person does not cause harm to others, his freedom must be guaranteed. This idea is accurate even in the case where such interference could produce significant overall gains in happiness.Notwithstanding the philosophical literature that builds upon Mill’s harm principle , 68, 76,Thou shalt love thy neighbour as thyself” [In Judaeo-Christian culture, a similar moral imperative stems from the Bible: “thyself” . In secuThe right to erase health and genetic information related to gender transition makes tracing genetic diseases impossible, especially relevant when dealing with their biological offspring. Thus, direct biological relatives should have access to a collected genetic sample as long as necessary to understand their genetic status better. This difficulty is not potential but of actual relevance because a line of thought gaining momentum is that transgender people should have reproductive rights. The truth is that transgender people may undergo fertility preservation gametes, usually before gender-affirming treatment. Therefore, some scientific literature calls for legal recognition of gender having in mind self-determination. It is stated that the relinquishment of reproductive capacity is no longer a prerequisite for gender transition, recognising that transgender people desire to be parents and are not intrinsically wrong parents merely due to their non-normative gender identities expressions. This perspective is based on equality and human dignity , 45, 59.Researchers might have to rely on medical records to study how health issues manifest differently based on biological sex at birth . ConsequThe right to forget gender-affirming health information could harm selection in terms of high-performance sports. It is not the purpose of this analysis to discuss the binary division in high-performance sports. However, it is well known that hormone levels differ by gender and that this influences sports performance. Although we agree with Lau  that basThe right to be forgotten regarding gender-affirming information might generate ethical conflicts with other circumstances, such as marriage and adoption, whose impediments (depending on the jurisdiction) might be violated by a gender transition. For example, at a marriage, a member of the couple transitions their gender. Different implications might occur as this relationship turns into a same-sex marriage. Depending on the jurisdiction, adoption, and the use of medically-assisted reproduction techniques might be restricted. In contrast, regarding the latter, suppose it is not restricted. The procedure might be endangered if medical history data have been deleted. As abovementioned, the discussion of recognising reproductive rights to transgender people is a matter of equality and human dignity.Also, in case of repentance: changing ideas is also an exercise of autonomy, which is why deleting gender-affirming health data can harm the owner, preventing them from exercising the most varied rights if data recovery is not possible;The right to be forgotten so far as gender transition is concerned might create the inability to trace the previous identity, and so criminal responsibilities could be avoided, as it would allow identification forgery; moreover, civil responsibilities could be jeopardised, as it might cause contractual and inheritance problems, for example. In this regard, Lau , which dAt this point, suppose we consider the right to be forgotten as a means to operationalise data protection and privacy, both conditions of identity. In this context, it makes sense to evaluate this legal mechanism for the entire exercise of identity in matters of gender transition. Hence, it is necessary to discuss the limits of the right to be forgotten regarding gender transition information, considering the principle of liberty and the proportionality principle as a foundation in human rights law. Based on these arguments, we argue that the right to be forgotten may raise ethical and legal difficulties in the following circumstances:Consequently, although the right to be forgotten is in line with the right to self-determination, there are ethical and legal doubts to ponder. Indeed, we presented sound arguments to support the non-deletion of health data. Still, there are already practical solutions to better collect health data from trans people and respect their privacy. Solutions are suggested by Deutsch and Buchholz  to improHuman beings are allowed a wide variety of personal choices influenced by their environment, culture, and psychology. This freedom in the sphere of individual decision-making—or self-determination–is the basis of self-fulfilment. On the one hand, recognising gender identity as a fundamental human right—in the sense of full development of an individual’s personality through self-determination and self-realisation—is accepted as an integral part of respect for human dignity. In contrast, forgetting gender-affirming health data should be regulated at the international level to protect the human person’s inalienable rights and future generations.Gender identity is intrinsically linked to human existence because it is present from birth, developing at the same time as a personality following the outer and inner worlds of the individual. So naturally, in any debate, there will always be different and complex cultural sensibilities influenced by the environment in which the individuals are inserted, whether it is public opinion influenced by the media and social networks, by political and economic interests, or religious beliefs. In this sense, we agree with Rich and Ashby  assertioAfter examining some inter-related and conflicting issues regarding the right to delete personal data, specifically medical and genetic records, in the context of gender transition, we conclude that the admissibility of this right should be limited and regulated. However, sound arguments accepted by fair-minded people supported by the principle of liberty and the proportionality principle should be the basis of such a decision.We argue that the right to delete should be restricted to data that do not risk the issues developed in this discussion. Indeed, given that it is impossible to forget by complete deletion, but only to hinder access, this problem’s total solution may lie in technology. It is required to invest in technology that guarantees the maintenance of the information necessary to comply with the restrictions indicated. Nevertheless, the fundamental question is the ethics that must be endorsed in the regulation of this matter. As so, data that affect any of the values referred in the hypotheses previously discussed, i.e., those which might affect the right to self-determination of other individuals, whether present or future, cannot be subject to oblivion, not even to definitive obstruction of technological access. Deleting health and genetic data can undoubtedly undermine the rights of direct biological relatives as well as generations to come, so we argue that erasing them might be considered ethically unacceptable. Gender identity is a personality-related fundamental value but should not prevail without considering other values because it should not be regarded as absolute.Regardless of the future of information about the past, it urges a discussion about specific features associated with the right to delete health and genetic data in gender transition from an ethical perspective. It is an issue that deserves broad and extensive exploration, which, along with other contributions, warrants bioethicists’ prompt attention.


The etiology and pathophysiology of sarcoidosis remains unclear, with epidemiologic studies limited by its relatively low prevalence. The internet has prompted patients to seek information about medical diagnoses online; Google Trends provides access to an anonymized version of this data, which has a new role in epidemiology. We hypothesize that there is seasonal variation in the relative search interest of sarcoidosis, which would suggest seasonal variation in the incidence of sarcoidosis.p-value less than 0.05 indicating statistical significance.Google Trends was used to assess the relative search volume from 2010 to 2020 for “sarcoidosis” and “sarcoid” in 7 countries. ANOVA with multiple comparisons was performed to compare the mean relative search volume by month and by season for each country, with a Our analysis revealed a significant seasonal variation in search popularity in 4 of the 7 countries and in the Northern Hemispheric countries combined. Direct comparison showed search terms to be more popular in spring, specifically March & April, than in the winter. Southern Hemisphere data was not statistically significant but showed a trend towards a nadir in December and a peak in September and October.Overall, these findings suggest seasonal variation with a possible peak in spring and nadir in winter. This supports the hypothesis that sarcoidosis has seasonal variation and is more commonly diagnosed in spring, but more evidence is needed to support this, as well as investigation into the pathophysiology of sarcoidosis to explain this phenomenon.The online version contains supplementary material available at 10.1186/s12890-021-01602-7. Sarcoidosis is an inflammatory condition of unknown etiology, characterized by non-caseating granulomas. More than 90% of patients will have pulmonary involvement, but sarcoidosis can manifest in almost any body system, including the lymph nodes, joints, skin, heart, and GI tract . Most inWith improving access to information through the Internet, patients commonly seek answers to their medical questions online . Google The term “infodemiology” encompasses the use of information obtained online “in the analysis, detection, and forecasting of diseases and epidemics, and in predicting human behaviour” in health . InfodemThe manuscript does not contain clinical studies or patient data. Google Trends data was extracted for each of the terms “Sarcoid” and “Sarcoidosis”, using filters for “Web Searches”, “All Categories”, “Worldwide” and from January 2010 to July 2020 , and the United States (USA). The relative search volume for “sarcoid” and “sarcoidosis” for these countries is found in Table Figures Of note, December–February, summer months, were significantly less popular than both winter  and spring  in Australia. None of the results from the other southern countries analyzed were statistically significant, but there was a trend toward lower search volume in December, and, less markedly, July–August. Overall, September and October, spring months, were relatively popular in the southern countries.With respect to monthly data, there was a statistically significant difference between months for the term “sarcoidosis” in Australia, the UK, and the USA. “Sarcoidosis” was more popular in March and April compared to the month of December in the USA and the UK. Furthermore, data for all three datasets from the UK strongly indicated overall variation (p = 0.0001–0.001), with relative search volume lowest in December and significantly different compared to the months of March to May. In addition, volume in December was significantly less than that of the months of June and July for “sarcoid” and both search terms combined.The results of this analysis indicate that searches for sarcoidosis are higher in the spring months, and significantly less so in the winter, particularly in the Northern Hemisphere. This suggests that the condition may be more commonly diagnosed in the spring. Overall, this seems to support findings of higher incidence in winter-spring, as observed in previous studies. Both the Minnesota and the Taiwanese studies showed lowest incidence in autumn, which was statistically significant , 7. The Our study assumes that patients only search for sarcoidosis online after contact with the healthcare system and when they are most unfamiliar with the term, that is, when they are first diagnosed. In addition, there is often a delay between when patients develop symptoms and diagnosis; a delay would systematically skew results. If sarcoidosis truly is most common in the winter-spring and least common in autumn, a few weeks’ delay would shift search patterns forward in time, making winter appear to be less popular, reflecting lower incidence in autumn, followed by the spring peak, corresponding to incidence in winter-early spring. Once they have been diagnosed, we expect that patients would preferably consult other sources, such as their physician, or resources provided to them by their physician, when their disease relapses. There are cases of seasonal variation in hypercalcemia in sarcoidosis patients, so it is plausible that this could also impact Google search trends in a similar fashion .Another important assumption was that the countries included follow a traditional four-season structure. We would expect opposing results when comparing southern hemisphere countries to those in the northern hemisphere; that is, that June–August would have the least search term popularity and September–November, the most. The results of the comparison of means in the southern countries showed mixed trends, none of which met statistical significance. December was less popular overall, but a smaller peak in interest was observed in September and October. The December phenomenon suggests that the variation may be due, in part, to a non-weather-related factor, but the latter peak is more consistent with the pattern observed in the Northern Hemispheric countries and true seasonal variation.The main limitation of our study was the nature of the data obtained from Google Trends. In the interest of maintaining privacy, Google Trends only provides relative search volume, and it is not possible to obtain absolute values. This makes it difficult to ascertain that the data is sufficient to make valid conclusions. Other countries with less access to internet or using search engines other than Google would be excluded, despite a relatively high prevalence of sarcoidosis. Lastly, the search terms used in this study were English words, which probably limited non-Anglophone countries from fulfilling the inclusion criteria.As mentioned earlier, the results obtained from Google Trends varies day-by-day; this is because Google Trends only analyzes a sample of the total searches . With biIn Moccia et al.’s study on trends in Multiple Sclerosis, the country selection criteria were more stringent, with a minimum relative search volume of 70 and population of 20 million to avoid “noise” from areas of less search interest . This waThe strongest data to support the overall results was obtained from the United Kingdom, which showed very significant data in every data set. This probably swayed the overall statistics for the Northern Hemisphere countries towards significance. The incidence of sarcoidosis is about to 11.5/100,000 in Sweden , but onlOur study adds evidence to the hypothesis that the incidence of sarcoidosis exhibits seasonal variation and is more commonly diagnosed in the winter & spring. It is expected that future work will be needed in determining how to best incorporate “infodemiology” and the wealth of Internet-based data into future medical research. Hopefully, the results of this study lead to more investigation into the etiology behind this seasonal phenomenon and better understanding of the pathogenesis of sarcoidosis.Additional file 1. Raw search results for term "Sarcoidosis" by month and country.Additional file 2. Raw search results for term "Sarcoid" by month and country.


Collaboration in personal interactions is hard; how much harder, then, is it to collaborate across temporal, geographical, or cultural barriers? Open science can be seen as a worldwide case study on peopleware—a major source of costs, but a huge asset.In discussing open science, one forgets that its key concept is  collaboration, which may be either accelerated or hampered by digital technologies. Collaboration in personal interactions is hard; how much harder, then, is it to collaborate across temporal, geographical, or cultural barriers? Open science can be seen as a worldwide case study on peopleware—a major source of costs, but a huge asset.In discussing open science, one forgets that its key concept is  The UNESCO draft recommendation on open science,th century, having been born with the first journals and records of correspondence among scientists. This notwithstanding, the more widespread understanding is that it is associated with digitally enabled scientific collaboration, through sharing the digital objects associated with research.Some point out that, since open science is an enabler of “collaboration without barriers,” it actually dates back to the 17This stress on the digital points out our dependence on technological enablers and the very many challenges posed by the many kinds of digital divides—social, cultural, economic, educational. This dependence has also prompted the continuous appearance of new kinds of computing infrastructures, standards, and frameworks to support open science. The associated terms “accessible,” “reproducible,” and “reusable” originated research in many fields in computer science and are key to understand this movement and the challenges it poses to information technology. “Reuse” in particular is fraught with undercurrents, since it also implies repurposing, and the fear this will produce undesirable side effects to one’s research. This is an example of the dual ways—advantage, barrier—people react to open science.The “open science ecosystem” of the InterAcademy Partnership Report,In this ecosystem, we recognize the most commonly cited pillars of open science, which can be summed up as hardware, software, and peopleware. The explicit digital component is restricted to the “E-infrastructure” component, involving hardware, software, networks, and repositories. Peopleware appears in all other components—e.g., as adopters of practices  are understood by researchers, data sharing—and open data in particular—are concepts whose realization are still in their infancy, with implementation, cultural, and political barriers. Perhaps one reason is that there are consensual understandings of what a publication is and how to share it. By the same token, the notion of software sharing through repositories is generically grasped by all who produce or consume research software. Incongruously, though everyone uses and produces data continuously, there are widely varying understandings of the concept of data. Consequently, data sharing is perhaps the biggest digital barrier in the open science ecosystem, not only because data is an asset and a commodity but also because many scientists are unsure of what kind of data they may share. While scientists in some domains  have a long tradition of data sharing, others  are unsure about how to proceed. This varies considerably across disciplines and geographic regions.In 2017, recognizing the impact of open data on research, FAPESP (the São Paulo Research Foundation) launched a multi-year initiative to implement open data policies. FAPESP is a pioneer in open science actions In its first stage, DMPs were compulsory only upon submission of large multi-year collaborative projects; by September 2020, they were extended to practically all of FAPESP funding lines. In 2017, virtually no one had heard about DMPs in Brazil or understood their role in a project. Considering that FAPESP receives annually on average 22,000–25,000 grant proposals, in all domains, this brought about a large—and sudden—culture change among researchers in the State of São Paulo. Since these plans are evaluated upon grant submission, and afterward their compliance (and evolution) is also analyzed within periodical reports, they soon became important elements in the quest for funding. Initially considered another bureaucratic demand, to be written and then forgotten, researchers are coming to realize their usefulness. This, in turn, is generating demands from researchers to their institutions—e.g., in assistance to write a plan or to help manage data for sharing. Even more important for culture change than the plans themselves is the message conveyed: in advancing knowledge discovery, open quality data is as important as open quality papers.FAPESP recognized that it is useless to ask people to plan data management if institutional repositories are not available. Thus, it instituted a WG with representatives from all seven public universities of the State of São Paulo to design and implement the infrastructure for open data. In 2018, the WG was joined by the Informatics Research Center of the Brazilian Agricultural Research Corporation, EMBRAPA. This network, publicly available since December 2019, hosts scientific data from research produced by the network members in all scientific domains; its design and construction involved more than 100 people across the institutions—administrators, legal officers, IT staff, computer scientists, librarians, and researchers from multiple fields.what not to do.The WG, coordinated by myself, started working in mid-2017 and comprised a mix of librarians and computer scientists with experience in interdisciplinary research. The entire enterprise took advantage from the accumulated expertise and experience of members of the Research Data Alliance (RDA),The network was conceived and implemented with openness and extensibility in mind. For this reason, early on we chose a solution of a federation of independent repositories, each of which would publish the metadata of the data files stored therein see . ExpertsWhen the pandemic struck, FAPESP immediately decided that researchers needed a comprehensive open repository of patient data to support data science initiatives for public health associated with COVID-19. It put together a public-private partnership of hospitals and laboratories that agreed to share their data. Under the technical leadership of USP, and thanks to the extensibility of the network, it was possible, in less than one month, to design, create, and deploy this repository, launched in June 2020,The creation of the network had three interesting side effects. First, because of institutional engagement, it raised awareness to the advantages and needs of open science in a country yet not familiar with this movement. Second, this in turn attracted researchers, who are becoming slowly engaged in associated activities. Third, being a pioneer effort in Brazil, it is being used as example to start similar initiatives in other parts of the country.A “federation of repositories” evokes digitally laden terms such as “networks,” “databases,” and “machines” and worries about the associated costs. These are the tip of the iceberg. What, however, were the lessons learnt concerning the rest of the iceberg—namely, what is required peopleware?Open science initiatives are long term and should not depend on the whims of personnel. Permanence assures researchers, who realize that these initiatives are not temporary and thus are worth the effort required . Sound institutional governance percolates up by example .The network participants created such committees, which were assigned a double task: creating and maintaining the institutional repository and providing assistance and training to researchers. In some institutions, this has percolated down to departments that are now creating their own groups to foster open science practices, e.g., in education or chemistry.Successful steering groups should include competent people with diverse backgrounds, in particular (1) someone with IT experience, for data centers, networks, and design and maintenance of repositories; (2) someone in library sciences, with experience in cataloging and archiving practices, ideally connected with expertise in data management; (3) people who practice data-centered research; and (4) someone from central administration.Such groups will only work if guided by common principles and composed of competent people who are willing to dedicate extra hours to promote and support the necessary culture change and influence budget decisions.No individual effort will succeed if the central administration is not convinced of the worth of open science, thereby promoting changes in institutional policies, infrastructure, and staff allocation. Also, no matter how much administrations are imbued with the spirit of open science, it will never take root without engaging the enthusiasm of researchers and staff.Had FAPESP not demanded compulsory DMPs nor instituted the network, open data would perhaps be less widespread in Brazil. Had researchers, as a consequence, not prodded institutions to provide the necessary infrastructure and staff allocation, there would not exist institutional policies to support open science.From the start, engage people who know how to navigate an institution’s internal power and political divides. No matter how technically competent, this kind of cultural change requires more than scientific knowledge.Our repository network involves 48 campuses and a large research center. All institutions already had sufficient hardware and IT staff to minimally create repositories and perform installation and integration tests. Each institution decided how to create its repositories according to its overall infrastructure, staff know-how, and legal constraints. The common metadata harvester interface was designed and developed by computing experts at USP and made available within the first 6 months of the WG. Had this kind of expertise not been available from the start, the entire project would have taken much longer. Lack of training of some IT staff led to disparities in local implementations.Initiatives will succeed if researchers are convinced of the usefulness to their careers. It is not enough that funders make them compulsory: the ones preparing shareable research outputs must believe that this is not yet another useless activity. This entails a continuous effort to convince researchers to use the repositories and help them to do so.Training of researchers and staff at different levels is needed—to embrace and support open science. People will only change their research/work habits if they trust the institutional environment—e.g., to provide archival facilities, to ensure credit is given where it is due. In our case, this prompted librarians to understand data stewardship. Not having been trained as such, the most common attitude is that “data are made from bits” and “publications are made from bits.” Thus, researcher support should be the same. Awareness of the differences is requiring that the more traditional librarians change their outlook on how to perform their activities.Given a person can play multiple roles in open science, researchers should involve all actors in research planning and design, thereby making all understand the wonderful contributions to knowledge building a project will bring about.Peopleware is an asset but also hampers the ecosystem. Due to its reliance on digital technologies, but also on organization of information, there is often a dispute between IT and library staff on who should “own” an institution’s open science policies and initiatives. Depending on how people are internally organized and connected in an institution, this may severely hamper the progress of any open science initiative.An obvious lesson, which everyone mentions but is hard to practice, because promotion or tenure structures do not recognize how hard it is to practice “open by design” and “plan for sharing.”Research requires permanent investment. It stands to reason that any kind of initiative toward collaborative research should also cost money. For some reason, there exist expectations that open science will save money. It does, indirectly, through reuse, learning from others, enabling new discoveries and transparency. Of course, there will always be a need for investment in, e,g, E-infrastructure (and maintaining it). A non-negligible cost fraction is culture change, which takes many years and requires time, patience, and enthusiasm of all involved. As such, the open secret of open science is that peopleware is its major and perennial cost—not only the producers of science but the entire ecosystem. It is also its major asset and, as such, should be treated, nurtured, and recognized.


Nonsense mutations are the result of single nucleotide substitutions in the DNA that change a sense codon (coding for an amino acid) to a nonsense or premature termination codon (PTC) within the coding region of the mRNA. The severity of nonsense is due to the interruption of protein translation by the production of truncated polypeptides not expressing their function. PTC-containing mRNA can be reduced by a surveillance pathway called nonsense-mediated mRNA decay (NMD). The lack of a functional protein due to a nonsense mutation can result in a number of different genetic disorders, e.g., cystic fibrosis, Duchenne muscular dystrophy, retinitis pigmentosa, congenital blindness, dystonia, spinal muscular atrophy, neurofibromatosis, lysosomal storage disease, Usher’s syndrome, hemophilia, Tay–Sachs disease, Schwackman Diamond syndrome, and several forms of cancer.Recent research is facing the challenge of targeting the genetic defect itself within the framework of a personalized medicine approach. Most clinical trials have been performed with small molecules that have been developed to target the translation phase and to promote the bypass of PTC, allowing the synthesis of a full-length functional protein, a strategy known as PTC “readthrough” by translational readthrough promoters (TRIDs). In this context, while aminoglicosyde antibiotics are considered outdated for use as readthrough promoters due to their chronic toxicity at higher dosages, Ataluren, a small heterocyclic drug, has been approved as a TRID for Duchenne muscular dystrophy under the trade name Translarna, and ELX02 is a new molecule that is currently in clinical trials for cystic fibrosis caused by nonsense mutations. On the other hand, the correction of the genetic defects at the DNA level has been attempted through modern genome editing strategies such as CRISPR/Cas9.REPAIRv2” could be a good alternative to restore the full-length CFTR protein [In this Special Issue, which aims to collect interesting research on this hot topic, both conventional strategies as well as new technologies are discussed . Through protein . Inherit protein . In part protein . Additio protein . Importa protein .Although molecular approaches fighting nonsense can be considered as a personalized medicine approach and may, in principle, appear to be a “niche research” topic as they concern “rare” genetic diseases, they can also be exploited for different pathologies. As such, they constitute a general approach to a basic genetic defect, widening the applicative scope and making the exploration of their mechanisms appealing.


The pandemics of COVID-19 and systemic racism have a deleterious impact on the daily life experiences and health for populations of color. The experiences are compounded for immigrant/refugee communities that may have other barriers such as English language literacy or trauma. Cumulative stress due to everyday racism is harmful for health.This study describes the impact of day-to-day lived experiences of Karen, Somali, and Latinx communities during the COVID-19 pandemic and aftermath of the police murder of George Floyd in the Minneapolis/St. Paul metro area.In-depth interviews were conducted over three weeks in September and October 2020 to understand the daily life experiences of Karen, Somali and Latinx adults drawn from community contacts during the COVID-19 pandemic and the aftermath of the police murder of George Floyd. Interviewers were bilingual and from the communities they interviewed. Nine questions were asked, ranging from their knowledge of COVID-19, prevention practices, experiences during shelter-in-place, and the perceptions of the police murder of George Floyd. Qualitative analysis included transcript review, coding facilitated by Atlas.ti Cloud software, summaries, and validation by interviewers.Thirty-two adults were interviewed . One-third were in person per participant request and complying with COVID-19 precautions, and the remainder were remote. The average age recorded was 37 years (range 20–66 years), 43.8% males and 56.3% females. Respondents reported experiences of discrimination and systemic racism while engaging in daily life activities, including accessing foods and common goods, school, work, transportation, and healthcare, all of which were exacerbated by COVID-19 and the police murder of George Floyd.Immigrant/refugee communities of color in Minneapolis/St. Paul face daily experiences of racism that were compounded by the events of 2020. Discrimination and systemic racism contribute to the persistent health inequities among populations of color. The U.S. is in the midst of a centuries-old pandemic of racism that contributes to health inequities for Black, Indigenous, and Persons of Color (BIPOC), including immigrant/refugee communities . Persist5Social and structural inequities for immigrants/refugees in the U.S. have also long existed, including institutional racism in health care . The Min121416The COVID-19 pandemic has amplified both awareness of the racialized systems and differential impact that immigrant/refugee populations of color experience. The inequities among BIPOC communities has been consistent since the beginning of the pandemic in early 2020 and contribute to the higher impact of COVID-19 on these groups 18192021.181920Particular to immigrant/refugee communities, a number of factors present differential risk and lead to poorer health outcomes and higher morbidity and mortality rates 1320212526.20212514271427292622132125The police murder of George Floyd on May 29, 2020 launched nationwide protests, the most fervent of which occurred in Minneapolis and St. Paul, Minnesota. Businesses and property were burned down and looted in the same neighborhoods at highest risk of COVID-19 —neighborThe purpose of this study is to describe the lived daily experiences of Somali, Karen and Latinx adults in the social and political context of 2020. It is imperative to understand how the immigrant/refugee communities’ experiences of the co-occurrence of COVID-19 pandemic and the aftermath of a police murder of George Floyd affect the daily life experiences of these communities in order to develop policies during and after the pandemic that mitigate—not exacerbate—pre-existing health inequities and social vulnerabilities.This study is an exploratory, qualitative study to understand the daily lived experiences of members of immigrant/refugee communities during the co-occurrence of the COVID-19 pandemic and the aftermath of police murder of George Floyd. It is rooted in a contextual constructionist framework . A constPurposive and snowball sampling were used to recruit adults 18 years or older from the Karen, Latinx, and Somali refugee and immigrant groups in the Minneapolis/St. Paul metro area. Participants had to have gone through the resettlement process to the U.S.; if U.S.-born to immigrant parents, they were excluded from the study. Recruitment aimed for variation in age, gender identification, socioeconomic status, and profession. Only one member per household was eligible.Data were collected using in-depth interviews (IDIs). Interviewers were recruited based on their interest in the research and representativeness of the Karen, Somali and Latinx community including proficiency in English and Karen, Somali and Spanish. Interviewers were trained in conducting IDIs over two sessions, practiced with a trusted source, and debriefed with the Principal Investigators for any revisions to the questions. Interviews occurred in September and October 2020. Interviews were conducted over the phone via video-conferencing software, or in person, practicing COVID-19 social distancing guidelines. Interviews were recorded with permission using a digital device and were transcribed. Interviews not conducted in English were translated from Karen, Spanish or Somali to English for analysis. Each interview lasted 30 to 60 minutes. Informed consent was obtained from each participant who was offered a $50 gift card for completing the interview. The St. Catherine University Institutional Review Board approved this research (Protocol #1442).The interviews included nine questions, although this manuscript focused on findings drawn primarily from two questions. The questions were 1) “In the past 3–6 months, we have all been experiencing shelter-in-place and transitioning to more open movement. Has the pandemic or the ‘shelter-in-place’ orders brought about additional strain with anyone in your household or elevated stress?” Prompts included concerns of safety, employment or loss of income, children at home, access to computers, language proficiency to help children with school work, and food access; and 2) “In addition to the COVID pandemic, the nation and the Twin Cities has had a rise in social unrest, police violence and destruction of property. In what ways has the aftermath of police violence, murder of George Floyd, impacted you?” Prompts included stress, afraid to leave the house, change in access to groceries, loss of businesses, and racial discrimination. Participant age, sex and ethnicity were the only demographics asked.Qualitative data analysis software (Atlas.ti Cloud) was used to code and analyze the transcripts. During data analysis, the team first read through all transcripts, built and refined a coding scheme, coded the transcripts, reconstructed the data into themes and patterns, interpreted the results, and checked findings with the interviewers. A disaggregated analysis by immigrant/refugee sub-group was done to ascertain unique experiences of each community group. The findings are a representation of many possible truths and experiences articulated by participants. From the research team’s perspective, knowledge and reality are socially constructed, so the research findings are one of many possible interpretations of how participants are making sense of the COVID-19 pandemic, George Floyd’s death, and the aftermath. With a focus on impact and experiences due to COVID-19 and the aftermath of police murder George Floyd’s death, each daily life activity was analyzed based on unique and targeted experiences of racism related to COVID-19, systemic racism, or both.A total of 32 adult participants were interviewed for this analysis . One-third of the interviews (n = 8) were conducted in-person and the remainder were conducted remotely. The average age recorded was 37 years (range 20–66 years). There were 14 (43.8%) males and 18 (56.3%) females interviewed.Daily life activities included in this analysis were 1) accessing food and essential goods; 2) school; 3) work; 4) transportation; and 5) accessing healthcare.Access to food and essential goods: Participants described the difficulties they experienced getting food and other essential goods, as well as the experience of discrimination and the fear of contracting COVID-19 while shopping for these items. Participants reported a rise in food prices and the subsequent consequence that federal nutrition assistance (food stamps) no longer stretches as far as it used to. Participants reported some difficulties, particularly early in the COVID-19 outbreak, in accessing necessary food and supplies because stores were out of supplies or limiting quantities that could be purchased. For example, one Karen participant described, “So we usually go to Sunfood, but they ran out of rice. The next place we went to was Sam’s Club to get rice, but they also ran out of rice.” While this was a common occurrence, the addition of the social unrest following George Floyd’s death destroyed businesses that for many immigrants/refugees was their only accessible source of food and essential goods. A Somali participant reported, “I have lots of friends that couldn’t find places to get food when the stores got shutdown. Thus, I had to take it upon myself to buy them food and go to stores for them.” A Latinx participant shared, “[There are] no stores anymore. I cannot go to the grocery store, I don’t have a pharmacy close, our bank, everything is gone.”Multiple participants reported fear of shopping for food and essential goods. Several described fear of contracting COVID-19 while out in the community and bringing it home to their family, like this Latinx participant: “[It] is stressful to live with the fear that you can get infected. You need to be away from people all the time. They cannot touch anything without you maybe getting infected. You can’t go to the store …because all is closed or restricted. [There are] no places to enjoy—just live with fear.” Other participants, particularly Karen, described fear related to the xenophobic environment that stemmed from COVID-19 being dubbed the “China virus.” Karen participants reported being targeted for and experiencing discrimination in the community for causing the pandemic. This Karen participant explained:There was this time where I was paying for my groceries, and I was trying to pay; this cashier was trying to get far away from me. They acted like they were afraid of me and like they were looking down on me. I don’t really understand it myself, because they were acting like they were trying to protect themselves. They probably thought, “This Asian person has the disease,” and they were trying to rush me; I paid for my things and left.Still others described fear related to the social unrest following George Floyd’s death. In some cases, participants explained the compounding effects of the social unrest, COVID-19, and systemic racism impacting their access to food and essential goods.Because of this we’re having to stay at home, not having much food, having low income, even [not] receiving information. So, this all comes together. So even with COVID or riots/destructions that has happened, it affects me and my family.” [Somali]Those just become a thought, but it does stop my learning and me from going out. It also stops us from getting food and also started economic hardship, like our family money. It’s really scary for us. [Karen]I can tell you many times where they stopped me at the stores or anywhere and try to verify if I’m buying something, who am I, who was there. They ask me for my driver’s license all the time. [Latinx]School: Participants discussed school from various perspectives: participants who are students, a member of a household with siblings who attends school, or a parent of children attending school. The daily challenges of school specific to the Karen, Somali and Latinx communities were linked to access to necessary materials, language and education, and support services. Not all families had access to the necessary materials for themselves or their child’s online education, including computer equipment that includes a camera and adequate internet access. One Latinx parent stated the need for support in the following way, “At school, Latino kids need more support…[schools need] to send the kids home with a laptop [with] Wi-Fi. Latino kids need more tutors because their parents have no education.”The most significant challenge to home-based remote learning was the parent’s English language learning status and their education level.The biggest problem is that we came from Asia and refugee camps, so we don’t know how to speak English. The laws and rules, we don’t understand anything. Since we came to America, things like computers, iPad or passwords, I don’t know anything about it. So now that they have online learning, I don’t know what to do. I go to school to pick [up] my child’s iPad and book, but when I come back home, I don’t know how to use the iPad. Things like what the teachers are saying and sending, I don’t understand anything, so this is a concern for me. [Karen][Much] of the homework was very difficult to understand…I have to talked to older women [who] don’t speak English [and] are in need to help their kids for school, and they don’t know what to do—they are very stressed out. Not many women have the education to use the technology to start with, even if they have some education—that’s not the same…we are in America, for example, the history class it’s not the same at the history class we took in Mexico. [Latinx]In some cases, the inability for the parents to help their children in school adds more family obligations to older siblings. As this Karen parent described, “Her older brother can help her, but if he doesn’t know how to help her, then there is no one who can help her with her homework. I can’t help her with her homework because I don’t know the language.” [Karen]Work/Vocation: Participants commonly reported substantial financial challenges due to COVID-related under- and unemployment. Participants described being laid off, having their hours reduced, and needing to be at home because of home schooling. These hardships along with increased household costs resulted in financial stress among many participants.Bills are higher because of the stay-at-home or being in the house more, using more electricity. And it’s hard to pay those bills when you can’t work and when you need the money that you’re getting for food for the children. How are we going to pay those bills if we cannot feed the children? [Latinx]I have been working for 19 years, and we have been told to just go home because of the pandemic, and that we have closed our workplace so just go home. [Somali]The social unrest following George Floyd’s death and curfew during and in the days after these events added to participants’ financial struggles. This Karen participant described, “When there is a curfew, I don’t get to work the full shift and [have to] return home. I am scared of the virus, plus the curfew. I get tardy and earn less money due to the curfew.” Others described trepidation going to and from work safely, as well as fear that the violent unrest would seriously destabilize their families’ lives :I think it was the second day of the riot when it hit Saint Paul. […] And then the buildings that burned down, it was very close to my workplace, so we were very scared […] that [our] building is going to be burned down. Because if it’s burned down, then I would lose my job. If I lose my job, how am I going to pay for the rent, and then if I/we can’t pay for the rent, then I might get kicked out of the house and [we] will become homeless, you know? [Karen]The damage in the aftermath of the social unrest did cause additional financial hardship among some participants. One participant clearly described this trauma and the implications for Latinx and Somali business owners.I do not agree with all the situation to break and burn stores. Most of the stores they damaged were family stores for Latino people or Somali people who live on Lake Street, and unfortunately the only people who was damaged was these families who have been working really hard to have their business, and now they’re gone. I don’t know I agree with the people who come and destroy the stores and steal and burn and break everything. That’s no point. That’s no real protest. We want to change the system, but that is not the right way, and it’s not fair, and the only people who really was more affected was the people of color itself—the Latino people the Somali people and the people who basically are poor. [Latinx]Even greater financial burdens were described among undocumented Latinx participants. One person described, “I’m so distressed because we lost our job, and we don’t, I don’t have the same income, and that affects me. I don’t qualify for a stimulus checks because of my immigration status.”One Latinx participant specifically mentioned that her financial vulnerability made her more vulnerable to virus transmission, because she does not have the type of job where she can work from home or afford things like grocery delivery. In her words:I think that as a Latina, it makes me more vulnerable, because for example, my supervisor and her husband can afford to work from home, they can afford to buy the groceries online and being delivery, and they can afford to pay the extra $10 charge for the delivery. It’s something that I cannot do, because I need to $10 dollars to pay stuff. So I guess people with low income are more vulnerable to be exposed [to COVID-19].Many participants described working in essential roles—healthcare workers, teachers, delivery jobs, retail, etc. Yet, many participants expressed the most concern about transmitting COVID-19 to family members. This Somali participant noted, “The biggest issue I was faced with was the pandemic, and just fear of bringing COVID to my kids after working, or them bringing it home causing me to spread it to those I work with.”Furthermore, despite statewide worker-protection mandates, participants described that they were applied inconsistently. One Somali participant described the positive measures their workplace was implementing:Yes, so I work at the [redacted]. There is a lot of problems. However, at my work, since the beginning of the pandemic, they have set strict rules, such as weekly tests, as well as you can’t enter the building without wearing a mask. Additionally, your temperature will also be checked to see if you have a fever. Therefore, then I hear some of the workers that are sent home, be told that they have a fever or if they test positive their told to stay home for two weeks.However, a Karen participant reported a negative experience:I am also scared of the virus, but my workplace said we could not stay home. Many of the workers asked to stay home and for the workplace to shut down, but they refused to shut the workplace down, not even one day. Even though we are scared, we have to go to work. If we don’t go, we will get tardy. We also don’t understand the law, and we can’t speak English. We also don’t understand the company rules, so I go to work every day.Despite many stresses associated with working during the pandemic and events after George Floyd’s death, participants also found new meaning in their work in the midst of these hardships. This Somali participant expressed deep meaning and purpose in her role in healthcare: “And then going into the health care field and just finding myself, finding my voice, finding how I can, you know, even step up from not only myself but for my patients, you know, and not be demeaned for being a black Muslim woman that’s bilingual in the healthcare field.” A Karen participant expressed renewed passion and purpose in her recent degree:I think when it comes to, in terms of health, we talk about George Floyd, we talk about police brutality, I think for me, I am personally really passionate about that, I just graduated from social worker department, so definitely [care about] policies, social justice, humanity, health, all these issues […] are very important for me. That’s why I mentioned that talking about hard issues and rude issues of racism, police brutality is very important.Transportation: Participants noted transportation challenges that exacerbated the above-reported daily life challenges, including food/supplies shortages, racially targeted interactions, and generalized fear of being stopped by the police escalated by George Floyd’s death. The COVID-19 food shortage and reduced hours required participants to travel farther to access goods, as noted by this Karen participant: “My car is broken down. It’s hard for me, because the store that is close is closed, so I have to go to a store that’s far, and when I come home [from work], the store is already closed. My car is already broken, so if I go further, it’s going to break more.”Participants also described generalized and accelerated fear of police racial violence, including traffic altercations. One Karen participant expressed, “Personally, I never get pulled over or stopped by the police, so I don’t know how to say it… But sometimes I’m worried about what would happen if police ever stop me. What are they going to do to me if they pull me over, because I am Asian, I am not white race?”Use of public transportation also made participants vulnerable to racist interactions. This Latinx participant describes, “Well it has affected me a lot. I mean, [I am] definitely harassed by racist comments— like I go to take a bus, and people in the bus tell me that they voted for president [Trump] so they can deport me.”Healthcare experience: Participants’ healthcare experiences can be categorized into access and experiences/perceptions. From an access perspective, many participants knew where to access healthcare and find a COVID-19 test. Many participants were receiving care for chronic conditions and, in general, those were being managed, albeit differently. In describing healthcare access for a family member, a Karen participant stated, “Well, she’s been going to like the doctor less than before the pandemic. She would often go like a few times a week, but now it’s like once like every other week. They also have a nurse coming in to check on her though. So, I guess that’s pretty good.”Despite access to care, participants shared the experience of health disparities from a personal perspective, related to family members and societal implications. The health disparities participants experienced were explicit, related to pre-existing conditions, equitable access to care and equitable access to information. One example is the consequences Asians experience due to COVID-19. One Karen participant describes it as,Yes, I have faced racial discrimination as an Asian or as a Karen person. Whenever I go, I’m scared that they might look down on me. They might think that I’m lonely or I smell bad. I’m really scared when I go to the hospital and I think that they might make fun of me and also might be unfair to me because I’m Asian.In other cases, participants reported fears and concerns about the hospitals themselves and what happens at the hospitals. A Somali participant said, “I have worries because so many of my relatives and Somalis have contracted the virus, and when they were taken to the hospitals, very few of them came back from the hospital. They all died, and that itself made me have so much fear.”Many participants described discrimination as an important cause of health disparities. Discrimination occurs at the system level and with individual healthcare professional interactions. As with other aspects of daily living, added racial stress due to police violence is compounded onto negative experiences with healthcare. One Somali participant described it as, “Also if you look at from COVID-19 perspective, with all that has happened with policy brutality, with COVID-19 and how some African American patients are treated, [they] are way worse because of medical racism.” Another example of the intersectionality of these issues is described by another Somali participant in this way,[The healthcare systems are not helping] the minority community, you know, on how to [get] better employment, [have] better procedures. [The healthcare system] is not dealing with healthcare discrimination, which is very evident, sadly enough. So that’s basically what we’ve been dealing with. And it’s very hard to see that, because you’re already dealing with the whole pandemic situation and then also dealing with the disparity side of it. It took a toll.COVID-19 is having profound economic and health impacts across the U.S. Mortality, unemployment, food insecurity and housing instability all have been elevated with persistent inequities among BIPOC communities . This pa15161720283042In this research population, participants experienced heightened fear of COVID-19 and systemic racism while engaging in daily activities. Consistent with trends nationwide, the pandemic brought with it increased economic insecurity and difficulties accessing food. Compared to non-Hispanic whites, Blacks and Hispanic adults had greater increase in food insecurity between 2018–2020 , greaterStress from struggling with daily life during the pandemic is compounded by co-occurring experiences of microaggression and systemic racism, whether at the grocery store, doctor’s office, or on public transit. This is consistent with experiences among BIPOC across the U.S., with 39 percent of Asian, 38 percent of Black, and 27 percent of Hispanic adults reporting adverse experiences due to their race or ethnicity since the pandemic began. Karen participants are doubly discriminated not only as a person of color, but also due to accusations they brought COVID to the U.S. Nationwide, violence and discrimination against Asian Americans during COVID has surged 48—hate c50Immigrant/refugee communities may be particularly triggered by witnessing police violence and/or experiencing racial discrimination due to the traumatic events that precipitated their resettlement . The Kar5758Previous trauma coupled with discrimination due to COVID-19 , increas161626769Addressing the upstream causes of inequities for immigrant/refugee populations requires a multifaceted approach. First, it is vital to engage community leaders in the distribution of information and be included in the decision-making spaces, even more so during community such as the COVID-19 pandemic and response and police violence . Immigra7118751227The final example is of political will. The officer who murdered George Floyd was convicted on April 20, 2021 – the first white officer charged due to the death of a black man . In addiThis study has several limitations. The sample size, sample selection method and qualitative methodology limit generalizability of these findings. Unique interviewers were used for each population group to represent each culture and language; therefore, the interview quality may have varied, resulting in a different depth of content among groups. The quality of interview transcription and translation also varied by language group, which may affect the comparability of disaggregated analysis. Due to COVID-19 adaptation, the interviews were conducted on the phone, video conference via computer or in-person using prevention practices. It is possible that this variation may have altered the participants full engagement in interviews by mode. Finally, limited demographic data was collected to respect confidentiality thus limiting understanding any variance due to education or economic-status.Immigrants/refugees are experiencing significant hardship on daily life during the co-occurrence of COVID-19 and the aftermath of George Floyd’s death. They are more vulnerable than other BIPOC groups due to specific vulnerabilities as immigrants & refugees . The added stress makes them even more susceptible to long-term mental and physical health impacts, suggesting the need for targeted public health interventions and social/economic policy and support mechanisms.


In response, the reconfiguration of health systems to encourage greater collaboration and integration has been promoted with a variety of collaborative shapes and forms being encouraged and developed. Despite this continued interest, evidence for success of these various arrangements is lacking, with the links between collaboration and improved performance often remaining uncertain. To date, many examinations of collaborations have been undertaken, but use of realist methodology may shed additional light on This paper seeks to test initial context-mechanism-outcome configurations (CMOCs) of interorganisational collaboration with the view to producing a refined realist theory. This phase of the realist synthesis used case study and evaluation literature; combined with supplementary systematic searches. These searches were screened for rigour and relevance, after which CMOCs were extracted from included literature and compared against existing ones for refinement, refutation, or affirmation. We also identified demi-regularities to better explain how these CMOCs were interlinked.Fifty-one papers were included, from which 338 CMOCs were identified, where many were analogous. This resulted in new mechanisms such as ‘risk threshold’ and refinement of many others, including trust, confidence, and faith, into more well-defined constructs. Refinement and addition of CMOCs enabled the creation of a ‘web of causality’ depicting how contextual factors form CMOC chains which generate outputs of collaborative behaviour. Core characteristics of collaborations, such as whether they were mandated or cross-sector, were explored for their proposed impact according to the theory.how and why collaborations work and can serve to inform both future work in this area and the implementation of these arrangements. Future work should delve deeper into collaborative subtypes and the underlying drivers of collaborative performance.The formulation of this refined realist theory allows for greater understanding of CRD42019149009.This review is part of a larger realist synthesis, registered at PROSPERO with ID The online version contains supplementary material available at 10.1186/s12913-021-06630-x. Global health systems are currently facing unprecedented pressures from a multitude of concurrent events, including limited financial resource, an ageing population, unwarranted variation in healthcare quality, and COVID-19 . Of courInter-organisational collaboration is often touted by policymakers as one of the means for solving the ‘wicked issues’ that contemporary health systems are facing. However, it is not always clear how collaborating will solve underlying issues such as financial pressures , 7. Likewhat determines a successful partnership, such as a local history of partnership working, effective monitoring and reviewing of organisational learning, having a shared vision, and development and maintenance of trust through behaviours and attitudes such as ‘fairness’, openness and honesty, sacrifice, and accountability. While useful to know ‘what’ leads to successful partnering, it is also important to explore how and why these features enable collaborations to be successful. Why does shared vision aid in accomplishing the aims of a collaboration? How does collaboration lead to improved performance?A variety of theoretical contributions have been made towards improving understanding of inter-organisational collaborations in healthcare, however, until now, few have attempted to turn a realist lens on the phenomenon –18. For explain how contextual features shape the mechanisms through which a programme works. This is achieved through testing and refining programme theories, expressed as Context-Mechanism-Outcome configurations (CMOCs). Initially, these are tentative ideas; as the review progresses and these ideas are brought into conversation with evidence (i.e. tested in relation to the evidence) they are refined to produce a more detailed explanation of how context shapes mechanisms . As. As18]. The purpose of this paper is to present findings from the third stage of theory refinement Fig. . DrawingThe literature for this refinement stage of our realist synthesis was identified through a combination of existing literature from prior stages , novel systematic searches, and grey literature sources , as is typical of a realist synthesis . An explWe included papers that 1) were case studies or evaluations (defined as reporting results of arrangements using descriptive methods), 2) report on an inter-organisational collaboration between healthcare providing organisations, 3) and were in English language, due to resource limitations of the study. Some papers had both literature review and case study portions, and these were also included, but data extraction was performed only on the case study parts. Selected studies were then subject to rigour and relevance checks in line with realist synthesis methodology.In line with guidance from Wong (2018), the screening for rigour was ongoing during the analysis process and aimed primarily to increase the trustworthiness of the findings . For casA custom data extraction form was created which recorded the study, collaboration type, primary driver (as best deduced from the study), CMOCs which fit into prior theory, and novel CMOCs , which did not fit wholesale into the prior theory. This type of custom form is typical in a realist synthesis and is included in additional file Using the existing realist programme theories from step two of this realist synthesis process as a base, we aimed to test our existing CMOCs against case studies and improve our understanding of how CMOCs are situated temporally and causally to improve our theory of collaboration in healthcare. This comprised phase 3 of our overall analysis , mergers (n = 7), joint commissioning (n = 6), vanguards (n = 4), primary care networks/partnerships (n = 4), (n = buddying (n = 2), provider chains (n = 1), alliances (n = 1), health boards (n = 1), networks (n = 1), quality improvement collaboratives (n = 1) and mixed partnership types (n = 1). Table Papers in the literature covered a wide range of inter-organisational collaboration types, including integrated care initiatives (such as Sustainability and Transformation Partnerships (STPs) and Accountable Care Organisations (ACOs))  and how these affect the process of collaborating.Extraction of CMOCs from included studies resulted in 338 CMOCs being identified, many of which were functionally identical and analogous to demi-regularities. The full list of these can be viewed in additional file Our initial CMOCs  identifia legacy of challenges led to a break-down in trust and dialogue and an entrenchment of organisational ‘fortress mentalities’ [Related to the level of initial faith is that of initial trust. Initial trust was put forward in phase 2 of our realist synthesis as likely to come into play in the ‘Connecting’ phase of collaboration, during which organisations seek partners and establish initial relationships . Contextalities’ . As trusalities’ , 76.During the ‘mid-life’ of a collaboration, a multitude of factors come into play which can help rapidly increase the level of trust, buffering against potential conflicts that may occur. Chief among these are ‘quick wins’ with a partner, which also help to increase faith , 76. TheWith respect to ensuring appropriate communication between collaborators, a number of contextual elements are key. Geographical proximity is one element that is difficult to mitigate, as a greater geographical distance between collaborators increases time spent building relationships significantly, by presenting a barrier to ease of arranging meetings and enabling informal interaction . GreaterConflict, for example, due to competition between partners, increases the difficulty in predicting the partner’s behaviour and increases the uncertainty in the decision to trust” [Conflicts between organisations can occur as a result of deteriorations in trust, as a result of ‘acute events’ such as failures on specific tasks, or from accumulating tensions caused by cultural distance , 42. Cono trust” . Reductio trust” . We alsoo trust” .most sources concur that a clear vision and/or mission statement should include attainable goals and that lack of clarity about vision can be a serious barrier to engagement” [This refinement stage further identifies that use of external, impartial deal brokers and committees can lessen the impact of conflict on trust by moving the locus of that trust to the third party rather than the partner , along wagement” . Here, eagement” , 63.So it is harder and less dynamic at the start, until you get a drumbeat going. Then it becomes easier because the peer group start doing it for you” [As a final look into the role of faith, a key mechanism which links into faith as an outcome is ‘the perception of progress’. The perception of progress is interwoven with faith - but is not entirely the same concept (as one can have faith without much perception of progress). The perception of progress is essential for ensuring that momentum is maintained and that there is no stall into what is termed ‘collaborative inertia’, a situation in which there is insufficient faith to maximise work on the collaboration . Having for you” . Affectifor you” , 56, impfor you” , and, imfor you” , 85.These various review findings suggest a web of contextual elements operating through many mechanisms, to produce many outcomes, forming causal chains Fig. . Some oftoo much was being expected too soon… as they were still working out how to function operationally before they could accomplish goals such as decreasing workload and improving care” [As trust and faith are maximised, work on managing conflicts, building collaborative structures, and establishing relationships, decreases. As a result, time and effort are freed up to create the conditions for collaborative ‘synergy’, which in our refined theory, refers to a willingness to engage in collaborative, rather than competitive, behaviour Fig. . Once ring care” .“Interviewees repeatedly said how difficult it would have been if their buddying arrangement had been imposed, and indeed those arrangements seen to be imposed by regulatory bodies appear to be have been the least successful” [.Achievement of this synergistic state is extremely difficult as many collaborative endeavours are ‘set up for failure’ due to initial contextual conditions being configured in such an unfavourable manner that it becomes insurmountably difficult to build the relationships required . These dcessful” .This information provides implications for cross-sector initiatives, such as ICS’ or ACOs taking place in the UK. In addition to many of these being mandated, cross-sector working brings additional challenges by requiring working between workforces of differing professional backgrounds. These professional differences manifest in a greater degree of cultural divide – a barrier which was referenced by many of the included case studies , 76. LikOur initial rough realist theory suggested that partnerships can be characterised along a spectrum of integration from full integration  to more informal endeavours involving fewer people  . Such diOn the other hand, ICS’ - which have now come into force in April 2021 - involve a significant number of large organisations coming together in a cross-sector manner, including local councils, primary and social care, and acute care [trust and its relationship to risk threshold may be replaced by confidence as a primary driver for collaborative behaviour in mandated or integrative collaboration types.Our programme theory suggests that formalisation through contracts may be one means of enabling collaborative behaviour in such a situation where initial trust is likely to be low or complexity very high. The following section explores further how In phase 2 of our realist synthesis, we identified a common CMOC which suggested that the formalisation of an arrangement through contracting facilitated trust relationships by having potential to act as a buffer where trust may otherwise be lacking . Inverse“to minimise uncertainties of behaviour by partners” had value in instances where trust was low [. Another source put forward the notion that formalisation through contract is “primarily about managing risk, trying to situate the risk with the organisation/s most able to mitigate it, and giving them the power to do so.” [. As such, we have added the concept of confidence, built through formalisation, to our programme theory diagram, as a determinant of risk tolerance ” [there is a need for a balance between power sharing and control, between processes and results, between continuity and change and between interpersonal trust and formalized procedures.”However, while some sources were espousing formalisation as a means for improving trust, it was evident that other sources were warning that over-formalisation could undermine the trust-building process, as “tuality” . This sections)” . These fctions)” . We hypoctions)” . As Casehow of the workings of the CMOCs we identified.Our review findings suggest that CMOCs formed chains of generative causality as a result of the Outcome of one CMOC becoming the Context for another. For example, a larger organisational size (context) leads to greater task complexity (mechanism), which affects people’s faith in the process (outcome) . HoweverThis phase of realist synthesis served to refine CMOCs identified in our previous paper to ensure these CMOCs are supported by case study evidence, while gaining further understanding of the temporal and causal links between them. Key refinements to the theory have included an enhanced understanding of ‘partnership synergy’ as changes towards collaborative, from competitive, behaviour, the formation of ‘initial faith’, which firmly situates multiple CMOCs into the early stages of collaborations, as well as ‘approach to conflict resolution’ becoming a mechanism that has a greater number of contextual factors changing its configuration Fig. . The degAttempting to simultaneously capture the various dynamics of inter organisational collaboration within one overarching theory is an enormously complex task. Indeed, one example alone cited Primary Care Networks as having 47 different potential organisational forms . Nonethehow trust is a necessary factor for engaging in collaborative behaviour.Our findings build on others in suggesting that trust is closely linked with the concept of collaborative synergy (framed here as ‘collaborative behaviour’) and mutual successes . Jagosh the strongest effect measured in the model is the overall effect of relational norms on project performance (including the mediating effect of partners’ trust and partners’ contribution)” [Also linked to risk tolerance was the concept of confidence, which came more into play when considering integrative or mandated forms of collaboration. Other sources not included in our systematic search indicate that when contracts are in place to uphold risk-sharing, benevolent actions are not attributed to free actions by the partner, but rather to the mere existence of the contract . This subution)” . Likewis. Both of these dimensions raise a number of implications regarding the notion of trust vs. confidence (or control) and their relation to risk  tend to be those that have evolved from pre-existing arrangements with effective leaders in place and a relatively strong history of collaboration, the addition of legislation which reduces flexibility may undermine existing ways that current ICS’ have developed . Both ofsk (e.g. ), indicawhere structures, positions and resources were aligned, this released the potential and unlocked barriers for purposeful collective action”. This corresponds strongly to our MRT and the notion of partnership functioning mechanisms being essential precursors to collaborative behaviour and the accomplishment of synergistic effects.Our introduction of the concept of faith, while relatively intuitive, is also one underrepresented in existing theories of inter organisational collaboration . Our finOur resultant framework bears similarities to others in other fields where collaboration is at its core, such as teamworking. One such example is a framework developed by Reeves & Scott (2010) for interprofessional teamworking. Teamworking is likely to constitute a subset of dynamics occurring within interorganisational collaborations . This frAlthough every effort was made to be as exhaustive with the literature search as possible, including multiple waves of systematic searching throughout the process, as well as searching grey literature sources such as organisational websites, it is nonetheless possible we missed out literature that would have been informative to the present review. A particular challenge was covering all of the partnership types due to the myriad overlapping terms used to refer to various collaboration types. Additionally, while some included papers did talk about collaborations which ended in dissolution  ), these One could also criticise the review for being UK-centric, however, we did include several studies from outside the UK, such as Austria  and the how does organisational size lead to a change in perception of task complexity? We could postulate that it is likely due to an ongoing cognitive appraisal within actors’ minds of the workload required, and that by having a greater number of other actors involved in the collaboration they thereby gain the knowledge that complexity has increased. However, we had to keep this review process manageable and, in many cases, we did not have evidence for many aspects at this level of ontological depth. As such, we have set out some signposts of where to explore, but this remains an aspect to delve into in further research.Lastly, depending on the level of analysis that one seeks to operate upon, it is possible to criticise the present theory for not delving deep enough. As previously mentioned, we had to stay at a relatively elevated level of abstraction in order to be able to encompass multiple types of inter-organisational collaboration. One could say that there are still changes to participant reasoning  occurring within some of the arrows present in Fig. what underlies the process of inter-organisational collaborations in healthcare, this paper builds upon our knowledge of not only what, but also how and why these elements work. This was achieved by performing in-depth extraction and qualitative coding of CMOCs present in 51 case studies and evaluative reports, and by forming hypotheses to produce a refined realist theory. This theory has cemented the interrelated roles of trust and risk tolerance, faith, task complexity, interpersonal communication, cultural integration, and synergistic effects with novel mechanisms, including 'perception of progress'. It also builds upon similar existing findings in the literature from other authors by linking contexts, mechanisms, and outcomes together. This allows an understanding of how initial environmental and interorganisational conditions set levels of trust, faith, and task complexity, and how these mechanisms can be managed later in the process of collaborating. Likewise, in mandated or highly integrative collaborations, the locus may be shifted from trust towards contractual obligation and a sense of confidence that the partner will act collaboratively. These chains of CMOCs were situated within a ‘web of causality’ which allowed us to depict how distant contextual items and their mechanisms work to affect more distal outcomes, including collaborative behaviour. We hope these theoretical advances inspire further empirical study and can prove useful to those seeking to establish collaborative arrangements between health organisations.While many existing theories have delved into Additional file 1.Additional file 2.Additional file 3.