This paper considers academic citizenry within Indian public higher education — a context where the increase in the enrollment of first-generation students and female students, due to affirmative action policies, has not substantially translated into altering the composition of academic staff. Informed by a mixed-method study conducted in 2019 with the participation of academics and those in leadership positions at four higher education institutions, we found that the enactment of such policies was operationalized for the production of the “New Middle Class” by universities. Of concern is that neither the representation nor the participation of academics who are women, “lower” castes, or minorities meets the mark of just, inclusive institutions. Despite the rhetoric of inclusiveness and development, the implementation of related policies clothe subalterns with the veneer of the intellectual class, permitting access on condition that sociocultural identities are concealed, and the hegemonic status quo maintained. Terms such as “quality” and “equality” function as tools for social control rather than serving social justice, where assertions of caste identity and resistance are simultaneously repudiated and misrecognized.The university is a highly politicized and fractious realm for students and academics. Amidst trade-offs between the processes of massification, democratization, commodification, and globalization, the question of transformation  We begin this paper by discussing a case of discrimination experienced by an academic in September 2020 in West Bengal, a region of India often lauded as more liberal and intellectual than the majority of the country. We do so because it brings to the fore the continued gendered and casteist marginalization and victimization of women and those groups deemed “lower” within the social hierarchies of Indian higher education institutions (HEIs).When a professor of History from Jadavpur University, Dr. Maroona Murmu, shared on social media her concerns that examination practices were placing students’ lives at risk during the COVID-19 crisis, casteist slurs were posted on Facebook by members of the student communities of Kolkata. One wrote that.It’s not about lagging one year but about how some unqualified and incompetent people take undue advantage of the reservation system and their caste is now helping them be successful, while the deserving lag behind forever. Our parents are stepping out, taking a risk every day to get us food, while some are sitting at home and getting paid for doing nothing. Ghosh, , n. p.Words such as “unqualified”, “incompetent” and “worthless” were used to describe the professor, with accusations that she was taking “undue advantage” of what was constructed as her “quota professor” identity. As the reader will notice in this paper — which offers an analysis of data collected in four universities in 2019 for a study on the politics of academic citizenry in Indian higher education — such a deficit discourse was echoed by many of the academics who participated. One such example of the binaries within this discourse was revealed in a statement made by a female associate professor (P15), which we chose for this paper’s title:There is a hell and heaven difference among faculties who are from quota and those who are non-quota.Dr. Marmu was hounded by over 1800 online trolls following that one social media posting. This was not the first of such experiences for her. She was quoted within the news media as being “appalled, but not shocked as she had been at the receiving end of casteist and racist slurs almost on a daily basis” within university spaces Ghosh, , n.p.. TEarlier that year, in a presentation at a colloquium about higher education organized by the first two authors of this paper at Jadavpur University,As soon as the Dalit or Adivasi person enters the academic space, institutionalized discrimination begins to repress them. They are made to understand that these spheres do not belong to them and they are to be always marginalized… [the] structure of the mental harassment, humiliation is so powerful that it curbs the wish to resist.She presented her counter-story of higher education, beginning with the hopes of her upper caste mother who had fallen in love with her Adivasi colleague while at university and later married in a rejection of caste-endogamous norms. With the cost of such difference extended inter-generationally, Dr. Murmu was made to pay the price for what can be seen as her mother’s transgressions of that deemed “legitimate” in marriage. Dr. Murmu’s treatment as “an exhibited strange object” in school extended through to postgraduate study where she was actively discouraged by her teachers from researching the “high culture” of classical music in eighteenth century Bengal because, as a “tribal”, she was constructed as not “qualified” enough. This deficit positioning from casteist discrimination has continued in her professional academic life, in incidents with students such as that recounted above, and with fellow academics who have accused her of using her caste identity to gain popularity and attract attention. In early 2020, her story of resistance as a marginalized academic was visualized in an art-based research project  for those castes previously marginalized — specifically the “Scheduled Castes” (SC), “Scheduled Tribes” (ST) and “Other Backward Classes” (OBC).The Gross Enrollment Ratio (GER) of students rose from 8 to 27.1% between 2001 and 2020, achieved through the 1043 universities in India, of which there are 386 state public universities, 48 central public universities, and 135 institutions of national importance AISHE, .Male students constitute 51% and female students constitute 49% of Indian students, with Gender Parity calculated as 1.05 for SCs and 0.97 for STs and 1.01 for the category “all”. The most recent composition indicates that OBCs comprise 37% of the total student population in Indian higher education, with SCs and STs comprising 14.7% and 5.6%, respectively AISHE, . HoweverIt is at the level of academic staff composition in higher education in India, the subject of this paper, where the inclusion of women, lower castes, and minorities falls far below the mark of equality despite the supposed pipeline from student quotas. Out of the 1,503,156 academics in higher education institutions (HEIs) in 2019–2020, 57.5% were men and 42.5% are women. However, gendered academic hierarchies emerge when employment positions are shown, as in Tables The gendered composition of academic staffing emerges in the different institutional types, as indicated in the table below.Further disparities emerge within the social stratification between institutions. The HEIs which are seen as more elite, the “Institutes of National Importance”, have a very low percentage of academics from SC and ST categories in their staff composition. According to the data shared by the Union Ministry of Human Resources Development, Government of India in 2019, out of the 6043 faculty members, at the 23 IITs, 149 were SCs and 21 STs Wire, .5 IntersSuch figures lead us to critically reflect on “why we are witness to possibly more than one lost generation of students who are yet to take their place as teachers” Nair, , p. 36 dScholars have analysed the historical and political processes that, from colonial times, have enabled the privileged upper castes to think of themselves as “casteless”. This is despite being inheritors of property, prestige, and power even as they continue to assert their moral and political leadership in independent India through their support for economic liberalization Alam, . While cWhat has become known as the “Mandalization of politics”Subramanian  outlinesThe post-Mandal phase again revealed the delusions of the self-perceived transcendence of these middle classes from caste-consciousness. The perceived threat from the reservations for lower castes increased their social anxieties and urgency to realize the preservation of their privilege. While they had no option but to make some space for the entry of different sections of the lower castes, large sections of the Hindu middle class were involved in “elite revolts” in response to the upsurge of the lower castes and in opposition to caste-based reservations privileged, and (mis)recognized in the two Middle Income Countries of India and South Africa.We adopted a mixed-method approach to study these institutions in two phases sequentially. In the first phase, data was generated from 136 participants of the 4 institutions who responded to a questionnaire of 34 questions in total, 25 of which were close-ended and 9 were open-ended. When the initial online response rate proved inadequate, despite the encouragement of snowball sampling, in-person recruitment was undertaken. The responses in this phase were analysed for statistical signification. In the second phase, in-person appointments were made with participants via email for semi-structured interviews, with snowball sampling encouraging further recruitment. The in-depth interviews were conducted face to face and lasted approximately from 60 to 90 min. COVID-19 restrictions prevented data generation from UI2; however, 37 participants were recruitment from 3 institutions  as outlined in Table Of the 30 academics not in assigned leadership positions, 13 were male and 17 were female; they included 17 professors, 7 associate professors, and 6 assistant professors. All 7 leaders were senior professors, composed of 6 men and 1 woman, with 1 director, 2 pro-vice chancellors, 2 deans, and 2 members of their institutions’ board of governors. In terms of social group, 35 participants belonged to General category, with only 2 academics, both from UI4, belonged to the “Scheduled Caste”.In what ways do you see relations to Gender equality (SDG 5), Strong institution for peace and justice (SDG 16), and Quality education (SDG 4)?Which structures and cultures in your institution do you feel need changing to attain the TFS?What are the markers of difference  in your institution?What do you understand by transformation for sustainability (TFS)?From your own experience, what enables/limits such power?Do you generally feel YOU have the power to bring about these changes?Following our discussion on the importance of TFS, can you discuss your choice/agency and autonomy in your teaching, your research, and when you engage as an academic/researcher within and outside academia?Questions posed during the in-depth semi-structured interviews were designed to elicit insights of the participants’ positionality, attitudes, and perspectives on transformation in higher education, and to shed light on the politics of participation within their institutions. In addition to questions about the history and cultures of their institutions, policy, and practice interventions, the interviews included explicit questions about whether the choice and autonomy of the participants enabled them to implement their beliefs about transformative change in higher education in the realms of teaching, research, and engagement with community. Selected examples of such questions included the following:How can universities deal with issues of social justice and serving marginalized communities?Does your university focus on it? If yes, how?What kind of challenges do you face?For those in leadership positions, additional questions included the following:Questions such as these were designed to enable participants to reflect and to share, for those with such critical consciousness, the challenges faced to enacting their beliefs, and the relevant costs involved when their capacity to tackle these challenges was threatened or constrained. We further tried to comprehend how participation was constituted in relation to markers of sameness and difference including those of gender, caste, religion, and various abilities. From those in leadership positions, we additionally enquired about tensions between existing policies and institutional initiatives, and their imaginaries of transformation as leaders. We hoped that by creating space for their reflections on their agency as leaders, and their perspectives on politics of belonging of marginalized groups in the institutional space, we would be able to comprehend their notions of social justice transformation in HEIs.Within the larger framework of the rise of the NMC, feminist lens enabled understandings of the insider perspectives of the academics and leaders, and their participation in the processes of incorporation of subalterns in university spaces. The “In this section, we discuss how tensions about conceptions of quality and equality underpinned participants’ narratives which, when probed, revealed intersecting and, at times, competing positioning by respondents. We then discuss how these seemed beset by denial, misrecognition, and blame shifting about the conditions of suffering faced by marginalized academic citizens.Tensions in the discourses of merit, equity, and equality underpinned many participants’ narratives. There was an overwhelmingly strong support expressed by those of the General category for meritocracy. In their responses they either implied or explicitly asserted that there should be a removal of social barriers from the criteria for entry to higher education and the ending of affirmative action policies. The continued indicators of casteism, in terms of awarding gaps in students’ assessment results, were constructed as politicized fictions rather than actual.the dominant in-group was experiencing.A female assistant professor from UI4 (P28), the Institution of Eminence, was deeply concerned about the “haves” and “have-nots” in the student body, between which she saw a large divide produced because of inequalities in their access to funding and digital devices. She expressed wanting to “give them a good direction”, “financial help” and a “little bit of guidance whenever they need it”, such that they would be enabled to take “good decisions” and “scholarships… jobs”. She constructed herself as the benevolent representative of the casteless General category, with the power and agency to grant favours to deprived, but deserving, students in the university. Despite this recognition of inequality, in her responses she expressed anxiety about how the politicization of caste on the campus was “becoming too big”, and harming the university by segregating academic citizens into SCs, STs, and OBCs. As a solution, she advocated blinding the assessment by removing “the ‘caste’ column from the application, I think will solve most of the problem” that The exception to the dominant assertion that quotas should be removed was the criteria for financial need, which was expressed by many. Participants recognized that the economics of competitive access to elite HEIs requires existing financial privilege. A first-generation male academic of the SC category at UI4 (P24) spoke at length about how access to resources was very important for becoming an academic. By way of example, he discussed how postgraduate fellowships offer “proper accommodation, proper food, and also safety and security” along with an “excellent culture of learning”. He emphasized that this was particularly the case for first-generation students from lower caste backgrounds without financial means who would find even the cost of photocopying a book prohibitive.A very few academics were certain that the reservations policy was of value for social justice. They questioned meritocratic assumptions of fair competition between those positioned unequally, such as in this excerpt from the interview with a male academic from the General category at UI1 (P4).… when 60% backward class, Dalits, or whoever, or even forward class poor people, if they are not getting the primary quality education, how can you think that they can fight?… They shall remain labourers. Reservation is perhaps the only means to make them empowered.This person recounted observing how affirmative action policies had led to educated Dalit members enter academia, the civic service, and the police, claiming that when viewed “in totality, it has served the cause of social justice”.One of the leaders, in a middle management position in quality assurance at UI1 (P10), who held national reservation policies as inviolable, nonetheless extolled that simplistic individualistic measures could address what he constructed as the internalized backwardness of caste. He sketched a deficit portrayal of student self-belief, and stressed that motivation was needed “to harness your potential energy and turn it in the right direction”, contending that the dominant group should act to “counsel such people” “so that they have self-realization… self-retrospection to extract out the latent potential”. Psychological, rather than social, solutions were most prevalently asserted to label those from the reserved categories as “vulnerable” personalities thereby dismissing the structural and cultural discrimination embedded in the fabric of the society. In other instances, educational solutions too seemed unconscious of the socio-cultural. For instance, a female professor within UI1 from the General category (P3) spoke about the importance of institutions offering “bridge courses” for candidates to prove themselves after initial support, rather than taking the approach of “filling the seats [of the reservation quota]… why should we strive for that? Is it a dinner plate?” Clear binary associations linked “weak” and “strong” with those from reserved and unreserved categories, respectively. Any engagement with the privileges of those labeled as strong and legitimate inheritors of social and educational capital, that is, those of the General category, was absent. Deficit constructions of those of the first generation extended across the hierarchy — from before their entrance as students to when they applied as successful post-graduates for academic positions. An associate professor in STEM at UI3 (P14) explained that she was completely against the quota system as it was “hampering the quality because they are not at par with the General category students”. According to her, “the reservation category students” should not be permitted to pursue engineering, implying that doing so posed risk “because engineers are making flyovers, and their skill and intelligence is so much important”. The exclusion of students from reserved category was attributed, by a senior professor at UI3 (P12), to various signs of their mis-fit with the norm, from a “lack of communication skill” to “being non-cosmopolitan”. Some of this had to do with their lack of proficiency in acquiring English language skills which excluded them from gaining access to NMC membership, as discussed earlier in this paper. This further confirmed why many first-generation students were failed from meeting the selection mechanisms that control access to quality education. This academic’s stance on the quota system being a serious hindrance to quality education was underpinned by constructions of deficit capital that reflect the societal bias which should be present in meritocracies.Ab yeh gobar mitti wale top karne lagenge to hamare bachche kaha jayenge?” which translates to “if these people who clean dirt become toppers, where would our children go?” This comment reveals casteist discrimination in its associations of Dalits with work related to foraging and cleaning, in addition to characterizing access as a threat to the dominant in-group and the self-interest inherent to the processes of judgment for selection. It is indicative of why meritocracy cannot succeed when hegemonic, exclusionary attitudes towards access persist in those with the powers of selection.Participants revealed how casteist attitudes pervaded selection, as shared by a female Humanities professor who recounted an incident which occurred during a doctoral selection committee meeting at UI1 (P7). The first few students were selected based on their results and accepted on the merit list. A number of those from SC groups were placed under the General category in the merit list in accordance with the existing reservation rules where the Court had reiterated that “the unreserved or general category cannot be treated as a de facto quota for upper castes”  shared how the university campus had “never wanted to look at gender as a unified category but always looked at intersections with gender”. Her experiences as a professor who had initiated a course on gender in her department had reduced her optimism when it came to questions of gender.… the gender question is never the primary question. So they say, ‘Ok, yeah, but are you gonna complain against a Dalit boy?’ So that becomes more important than whether she’s a Dalit woman who has faced both upper caste patriarchy as well as her own community’s patriarchy.She believed that female students of lower castes, unlike the conditions created for the new Indian woman and for their male counterparts, suffer greater discrimination that is rendered invisible by the politics of representation. Scholars have referred to the “casteist and exclusionary” nature of the students’ movements on campus which have ignored Dalit women’s interests , specializing in Dalit Studies, shared how “most of the faculty members, they work with this kind of an elitist mindset” and those from upper-caste background were “reluctant to guide the students from the marginal communities, especially the first-generation students”. In this own academic practice, he tried to do “some kind of justice to the students who come from these kinds of background”. However, he pointed to the continual societal influence which reduced opportunities for access. One was the claim that male children are given preference to be the first of their family to access higher education. This was an explanation provided for the larger participation rate of first-generation male academics, in addition to the continuation of patriarchal cultures within that peer group. He described this as.a kind of clash of interests… some of the Dalit girls, they told me personally that, ‘Sir, there is a gender discrimination among Dalits… the Dalit boys, they always like the Black-Americans.’ They follow black patriarchy, right? So there is a commonality between the Black patriarchy and Dalit patriarchy.koyla haath me lenge to kala to hoga hiIn another instance, a professor in the Humanities at UI1 (P7), who was very vocal in her protest against injustice in the university, believed “in putting in my effort because somebody who comes after me will have a little courage to go a little ahead of the point that I have reached”. She spoke of an incident that she believed reflected the complex realities of relations of power in universities. When a Dalit male PhD scholar was accused of plagiarism by his upper caste female supervisor, fears of “Dalit atrocities claims” infringed on disciplinary processes leading university authorities to be slow to respond or be seen to choose “sides”. The outcome was changing the supervisors to ones which graduated the student. She felt that “this is one side of the story where the powerful and strong Dalits who have got connections and they have connivance with the upper caste people”. What is also of interest is that an upper caste male colleague laid the blame on the female supervisor for taking on the Dalit student in the first place, using the discriminatory idiom, “Some female participants felt that the approach to the inclusion of those with other markers of difference, such as from caste or religion, had the effect of reducing the emphasis on equality for women. One female academic in STEM at UI3 (P14) adopted the myth of meritocracy uncritically as she ridiculed the students admitted on quota, saying that “they would be looking at teachers as if they are being taught in Urdu or Pharsi (Persian language)! They don’t know anything”. The discourses she used reflected her perceptions that the category of “woman” is homogeneous, and hence was ignorant of the ways in which “caste and gender subjectivities were shaped by intersection of both privilege and oppression, making way for positions of domination and subordination to work in complex ways” Dhawan, , p. 135.While the previous section discussed institutional spaces not being friendly to students in reserved categories, also evident in the data was continued denial of discrimination and exclusion, and a lack of reckoning with the misrecognition of social groups with markers of difference.One professor in Health Sciences from UI3 (P15) shared her concern about academics from reserved categories. As an upper caste academic, who did not support reservation of any kind, she suggested that there may be a developmental culture emerging from, or affinity empathy held by, those of the younger generation, including students, for staff who had been granted access through the quota process.If a non-quota faculty teaches badly, they [students] revolt. And maybe for quota faculty, they are more sensitive and don’t always revolt. They think it’s better not to complain since the faculty is appointed through quota.Of interest is that this respondent did not express surprise that students were privy to this knowledge about staff members.Wide and divisive social and intergenerational gaps between those in academic communities were described as having created an “epistemological struggle in the university space”, an apt insight by a first-generation male professor from the SC category at UI4 (P24). In this section, we discuss the nature of responses to such struggles as they were expressed by the dominant in-group’s denial of systemic and social injustice.A dominant narrative, most strongly asserted from participants at the institute of technology UI3, was that there was no discrimination, especially on the basis of caste, between academic staff. As such, we offer insights specifically from that HEI. For instance, a woman leader (P23) who was a member of the Board of Governors explained that.once the students come into the institute, they largely start from the same blank page. Within the institute… I can say about my institute with lot of confidence, that you will not see any kind of discrimination et cetera, in terms of various communities or castes et cetera. it doesn’t figure in the public discourse in any way at all.It is possible that the overt focus on issues of gender discrimination from those at the institute of technology was possible because the percentages of female students and academics were very low. Not only did they question the associated gender stereotypes, they supported reservation policy of 14% for female students. This commitment to gender parity was not extended to the under-representation in terms of caste. When it came to the quota system for OBC/ST/SC, 10 out of the 13 respondents at that institution did not support it. Common discourses constructed the latter as a system “diluting the quality of education” as expressed by a female academic (P15). A male academic, an assistant professor in the Humanities (P11), described caste reservations as a “big road block… here in India we are just forcing them to go to higher education by giving them this kind of lolly pops” which he saw as against the public good as “big blow for the country”. In his responses, this respondent not only constructed his colleagues from such social groups as undeserving others, but clearly indicated the entitled position he placed himself and the social grouping to which he identified. We found that even those who saw themselves as sympathetic to the groups previously marginalized, indicated the limits of their commitment to social justice. The sentiment of one male leader, a senior professor in STEM who was associated with UI3 for three decades (P22), echoed by many, was that only one generation should benefit from affirmative action, and that “once they are given, no further”. Many did not recognize reservation as a mechanism of addressing societal inequalities and historic injustices, rather constructing it as unfair that groups other than their own had access to financial privilege by virtue of caste-based quota s. An assumption was that a single generation of recipients of the quota system was sufficient opportunity for success of persons from such groups within India’s stratified society.Most prevalent in their narratives was a denial of any problems of exclusion or discrimination in their midst, which led to their dismissal and misrecognition of such experiences of their marginalized colleagues. What was most evidently lacking was historic awareness of the country’s constitutional commitments and the university’s role in such transformative change. What was more often repeated were a number of urban legends about the supposed abuse of the quota system. One was that of SC/ST/EWS certificates being bought by the wealthy for access to higher education. A professor from STEM (P15) claimed that,If you check, you will find the people of remote rural areas or poor tribal families, who really need reservation cannot come to study here. Scheduled Castes or Scheduled Tribes students who are entering HEIs through quota have 4 to 5 houses, all in their family are well established and still using quota to get facilities and there is no dearth of money.A number of such tropes littered the transcript of an interview with an academic from the Social Sciences, an associate professor who included gender and sexuality issues in her teaching (P19). While on the one hand describing facing “a lot of non-cooperation from male faculty members”, on the other, she declared caste an “obsolete concept”.With such tropes came expressions of moral outrage voiced by many of the participants across the institutions, which often constructed the speaker as benevolent towards the most vulnerable. For instance, one male academic, who was a professor from the Arts and Humanities at UI1 (P1), saw the caste system as an illness of the system. He suggested an evaluation of the efficacy of the quota process for social justice by calling for an “analysis of the system… to see who all gained and who all didn’t gain from the system. And those who benefitted, are they really empowered? And finally, the society which we wanted to change through this system, did it change at all or not?”.within the academic community too, as we discuss in the next section. This can be seen as symptomatic of the denial and misrecognition discussed in this section, which confirms Deshpande’s  who attributed the mental ill-health endured by those marginalized entrants to government affirmative action policies. He stated, “Instead of equipping them properly, government make their entry through quota. And after they enter, they become mentally unstable, or commit suicide. Even if they continue initially, they finally drop out”.Similarly, a female academic in STEM at the same institution (P14) expressed that “because the government is compromising, everyone is compromising, and finally when the result comes it is the degradation of the whole system”. When asked during the interview whether she perceived that reserved category students felt humiliated by such associations, she intimated that within the classroom “sometimes they share and say that they feel bad when they are told all that”. Her advice, albeit benevolent, reproduced a culture of performativity to meet the expectations of the gaze of the dominance in-group.You better show them; you get good grades. Prove to them that you are capable and it is not only because of your reservation you are here. If you you are capable, you crack an exam and show them.In their bid to mask the structural hierarchies and violence prevalent in higher education institutions, these were attempts of privileged academics to blame, dismiss, repudiate, and marginalize the discriminatory experiences of students from reserved categories.A first-generation male academic in the Arts and Humanities at UI4 (P24) saw a correlation between the socio- economic background of students and suicide rates in higher educational institutions. He critiqued his colleagues as operating with an “elitist mindset” that sustained an institutional culture of apathy towards such students, where their teachers did not invest in nor sustain students’ hope. He believed the untransformed casteist culture fed into such unwillingness to support SC or ST students.I noticed in our university, especially in Social Sciences, that most of the faculty from the upper caste background, with a middle-class identity, they were not willing to… were reluctant to guide the students from the marginal communities, especially the first-generation students.While most of what he described was at the interactional level, he was in favour of focusing on systemic and structural issues which could lead to institutional plurality, instead of targeting individuals for social mobility or concentrating on socio-cultural identities.Against the norm, a small minority of our respondents saw the experience of belonging of academic citizens as sitting within their sphere of influence. This first-generation male academic (P24) shared,.I feel, at least in my capacity, I try to do some kind of justice to the students who come from these kinds of background… even losing one life is also precious… [the] institution should take the responsibility to sustain them once they enterHe described how the dominant culture made it is easy for colleagues to blame the victim, not only in their thinking but also practically, such as through approaches to closing cases of caste or gender discrimination. Another participant (P29) spoke about how the aftermath of a suicide had been handled. He was concerned that in the face of a “very politically charged” situation where “various entities were trying to take advantage”, there had not been adequate approaches to seek solutions to ensure it does not happen again.nobody has talked about any systemic issues that have led to that death. Was there any systemic issue, were there any structural issues, which need to be addressed? Gap which needs to be plugged…to prevent something like that from happening again.He also spoke about a lack of accountability about issues where exclusionary practices of bullying may have played a part , and that the status quo of the conditions which lead to such mental ill-health “remains the same. So you have not… actually done any service to any possible institutional changes”. Similarly, another assistant professor (P31) in Health and Life Sciences at the same institution (UI4) discussed the difficulties such students face in finding willing supervisors because staff “have an attitude that I will not take any students who is coming under the reserved category”.A “gender person” who was an associate professor (P33) noted that the effects of the exclusionary conditions were pathologized as atomized at the individual level, rather than being informed by the collective resources of those within the university who could contribute to more social models of understanding transformation systemically.[on] this campus suicide is a contested fraught concept and even for people who’ve been involved and been thinking about it, [it’s] difficult for us to articulate that question. But they would have… a medicalised question.Within this paper, we have located our argument in the discourse of the rise of the New Middle Class (NMC) in India from the 1990s (Fernandes & Heller, While the constitutional obligation of social justice has spurred the rise of NMC in public universities, it has simultaneously revealed a shamelessly pretentious commitment to social justice (Visvanathan, Of all to emerge, it is perhaps the figure of the subaltern woman (Bhatt et al.,


Open Access funding enabled and organized by Projekt DEAL.The article “Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review” written by D. Huber, S. Seitz, K. Kast, G. Emons and O. Ortmann was originally published electronically on the publisher’s internet portal on March 05, 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The original article has been updated.


Death is inevitable. Grief following a death is universal. In expressing the loss of loved ones, grief differs across cultures and individuals. It may vary depending upon the circumstances and the person’s ability to cope with the loss of their loved ones . The proDifferent families react to ambiguous loss differently. Certain family members fail to overcome this despair and grief and are described as “living in limbo” spending their whole life in anticipation of their loved one’s arrival. Internal closure never occurs, and such families are never at peace and never move on. Conversely, other families move on and end the grief by taking robust decisions , 6. ThisThe Ethiopian Airlines flight ET-302, a Boeing 737-MAX 8) crashed shortly after take-off from Addis Ababa Bole International Airport (HAAB) in Ethiopia on March 10, 2019, at about 05:44 UTC killing 149 passengers and seven crew members [37-MAX 8 The author conducted a telephone interview with a close family member on June 12, 2019. The Nepalese victim’s family declined to provide a DNA reference sample. However, they provided some relevant AM data, which was then communicated to the INTERPOL office of Nepal. They made a decision not to claim the human remains of their loved one, which was unconventional, but courageous in the author’s opinion. On asking, “under what circumstances was this decision taken”, they replied, “they are aware of the fact that her remains cannot be retrieved” and “funeral rituals according to the Hindu tradition shouldn’t wait”. Thus, they completed the funeral rituals with the charred soil collected from the crash site. It was their choice for a final goodbye.Ethiopian Airlines flight ET-302 crashed, killing all passengers and crew members from 35 countries . Nearly In situations like this, people can be frozen and immobilized by ambiguous loss, which prevents them from beginning the mourning process . In the During incidents like this Ethiopian airline crash where there may be limited chances of the recovery of the remains, the families should be thoroughly informed on the possibilities and permitted to make the decisions that they feel are best, without others telling them what they should do. In unlikely situations, which do not allow a return of identified remains, all information should be passed on to the family members. This can allow them an opportunity to complete the last rites according to their culture in timely manner. This may bring closure to the families who have lost their loved ones in any conflict or disaster.


Classic psychedelics, such as psilocybin, act on the brain's serotonin system and produce striking psychological effects. Early work in the 1950s and 1960s and more recent controlled studies suggest benefit from psychedelic treatment in a number of conditions. A few case reports in recreational users and a single experimental study suggest benefit in patients with obsessive-compulsive disorder (OCD), but careful clinical data and long-term follow-up have been lacking. Here we describe a case of a patient with refractory OCD treated with psilocybin and followed prospectively for a year, with marked symptomatic improvement. We provide qualitative and quantitative detail of his experience during and after treatment. Improvement in OCD symptoms (YBOCS declined from 24 to 0–2) was accompanied by broader changes in his relationship to his emotions, social and work function, and quality of life. This individual was an early participant in an ongoing controlled study of psilocybin in the treatment of OCD (NCT03356483). These results are preliminary but promising, motivating ongoing investigations of the therapeutic potential of appropriately monitored and supported psychedelic treatment in the treatment of patients with obsessions and compulsions. Obsessive-compulsive disorder (OCD); psilocybin, case report; treatment. Thus, tPsilocybe mushrooms), for various psychiatric disorders. Recent controlled studies suggest benefit after one or two doses of psilocybin in major depressive disorder . Careful study is needed to follow up on these observations.Research on the use of psilocybin in the treatment of OCD is more limited. Early case reports suggested improvement in OCD symptoms after use of psilocybin and LSD . Later, We have begun a double-blinded, randomized placebo-controlled trial of single-dose psilocybin in treatment-resistant OCD (NCT03356483). Here, we report the experiences of an early participant in this trial who experienced rapid and lasting improvement. It is important to note that this response is not typical – we have seen cases in which improvement was less dramatic, and cases in which there was no significant change at all. Our goal in presenting detailed qualitative data here is to provide the field with insight into the subjective experience and correlates of change in a responder, for the benefit of clinicians interested in such work and to inform theories about underlying psychological and neural mechanisms.Various theoretical rationales for the use of psilocybin in the treatment of OCD have been proposed, at different levels of analysis. At the neurotransmitter level, serotonin reuptake inhibitors are the best-supported class of pharmacotherapy for OCD . Since pAt the brain network level, psychedelics may acutely and adaptively modulate the default mode network, in which dysregulation has been proposed to contribute to many forms of psychopathology . ChangesAt the psychological level, the acute mystical experiences  evoked by psychedelics have been shown to correlate with symptom improvement in several clinical contexts . It has At a more basic psychological level, the potent thoughts, feelings, and memories that emerge during a psychedelic experience may provide an opportunity to form both new insights and new ways of relating to and responding to inner experience. For instance, patients may learn a process of awareness, acceptance, approach, and “letting go” of emotions to replace a rigid emphasis on controlling, suppressing, or avoiding them . Emotion2Daniel (a pseudonym) was a 33-year-old man who presented for participation in an ongoing randomized controlled trial of psilocybin for treatment-resistant OCD (NCT03356483).Daniel reported a primary diagnosis of OCD and a history of a major depressive episode, Tourette syndrome (TS), and panic disorder. The diagnosis of OCD was confirmed by a doctoral-level clinician (BK) and an experienced interviewer (SK) using the Mini International Neuropsychiatric Interview, Version 7 MINI-7; . Daniel Although Daniel reported some success in coping with his OCD symptoms using compensatory strategies and personal resources , he continued to struggle in managing his emotions. He found his social functioning, hobbies, and work to be detrimentally affected because of both his OCD symptoms and his difficulties managing emotions.Daniel reported OCD symptoms since his early teens, with multiple episodes of treatment and limited response to both psychotherapy and pharmacotherapy. He reported four past exposures to psilocybin mushrooms, twice in his early 20s and twice about 2.5 years prior to his participation in the current study. He reported finding that these mushrooms provided some help for OCD symptoms in that they reduced “static” in his mind. These benefits were transient, lasting 1–2 weeks, and did not occur every time. He reported that effects appeared related to his mental preparation. He stated, “I recall one instance where I expected some relief and received none. I hadn't put anything into the process and so the drug didn't give anything back.”He also reported a single use of LSD, about 1.5 years prior to participation in the current study; he reported minimal, if any, benefit to OCD symptoms from this experience. At the outset of the current study he was hopeful that treatment with psilocybin would provide some symptom improvement but expressed a realistic understanding that it was unproven and the benefits, if any, were impossible to predict.2.1This study has been approved by the Yale Human Investigations Committee (HIC #2000020355) and is conducted under an Investigational New Drug (IND) permit from the U.S. Food and Drug Administration (IND # 34406), under the Schedule 1 DEA certificate held by corresponding author (BK). The participant consented to the description of his treatment in this report.Daniel worked with two study facilitators (SK and GD), both of whom had Master's degrees, extensive experience working with individuals with psychiatric symptoms , workshop training in the facilitation of psilocybin dosing sessions, and prior experience facilitating dosing sessions under the supervision of an experienced doctoral-level facilitator.https://pharmacy.wisc.edu/centers/zeeh-pharmaceutical-experiment-station). This dose is in the middle of the range (0.20–0.30 mg/kg) that typically produces a robust psychedelic effect and has been used in other recent therapeutic studies and falls between the higher two doses used in the one previous study of psilocybin in OCD . Psilocybin  was provn in OCD .Daniel, the facilitators and the study rater were blinded to condition (psilocybin vs niacin 250 mg) at the time of dose administration. The primary outcome measure for this first controlled study of psilocybin in the treatment of OCD is 48 h after dosing; this time point was chosen to focus on rapid symptom changes and so as to have our primary outcome uncontaminated by retrospective psychological processing during integration sessions, which began after 48 h. Daniel and the facilitators were formally unblinded to dosing condition at 48 h post-dosing. The study rater was unblinded at one-week follow-up, because participants who received placebo were not followed beyond this point (they were offered the opportunity to receive open-label psilocybin). The facilitators conducted follow-up psychological integration sessions at 48 h and at one, two, and 12 weeks post-dosing. Clinical assessments and ratings were conducted at 48 h post-dose (primary outcome), then at one week, and at two, four, eight, and 12 weeks. All sessions were recorded and later transcribed, permitting the extensive verbatim quotes provided in this report.The facilitators spent time getting to know Daniel prior to the dosing session and provided nondirective support during the session, in line with past work that has suggested the maintenance of an environment of psychological safety during dosing can help to prevent ‘bad trips’ . No stru2.22.2.1In preparatory sessions, the facilitators provided guidance for the upcoming dosing session. This included discussion of session procedures, psychoeducation on the range of possible acute effects of psilocybin, and the potential for clinical change with either psilocybin or placebo. Responsibilities of facilitators were discussed, and there was a focus on developing trust and rapport between the study participant and the facilitators. Additionally, the facilitators provided guidance on how to approach any experiences that might arise during dosing. The aim was to foster within Daniel a curiosity about the contents of his mind and a willingness to accept and “walk into” whatever thoughts or feelings might emerge during the dosing session.The facilitators also explored Daniel's behavioral and cognitive patterns, his relationship with his emotions, and themes important to his overall functioning. There was some exploration of his OCD symptoms, the concerns and motivations underlying them, and the impact of these symptoms on his life. However, only a minority of preparation time was focused specifically on OCD symptoms, and they were not directly targeted for change. In the facilitators' view, Daniel's general patterns of relating to and processing his emotions were an especially important target. The predominant focus in preparatory sessions was thus on teaching Daniel about the nature, purpose, and constructive use of emotions.As the facilitators explored Daniel's history, he showed great discomfort with the experience of negative emotions and a lifelong pattern of “compacting” and avoiding his emotions. This repeatedly led to these emotions building up and overwhelming him, and he described himself as emotionally “fragile.” He also described extensively analyzing situations to identify what he “should” be feeling or doing, then trying to steer his feelings and actions based upon these formulations. He was troubled by questions of how many of his life choices and circumstances were dictated by these formulations rather than by his authentic desires. Further, he perceived a troubling incongruity between what he tended to think he should feel versus the feelings he actually had. He also had substantial difficulty sharing feelings with others and tended not to disclose them. As a result, he lacked the kinds of deeper connection with others he desired and believed he was not truly understood as a person.The facilitators explored meaningful episodes in his life to uncover what was important and personally fulfilling for him. They paired this with an exploration of how he wanted to live his life moving forward. Daniel noted that, during the most meaningful times in his life, his “guards were down,” he was “okay with feeling,” and felt “almost OCD-free.” The facilitators highlighted how he was neither suppressing nor avoiding his emotions during those times, but was, instead, open to and connected with them. The facilitators also highlighted his intelligence, curiosity, and creativity and explored how he might apply these qualities to his life alongside an openness to his emotions.Near the close of the second preparatory session, an intention for the dosing session was established to anchor his experience. By this point, Daniel expressed a desire to “slow down and let myself feel things” and “to be more honest about what moves me.” Proceeding from this desire, he developed an intention for the dosing session to be open to the breadth and depth of his feelings, and to be honest with both himself and others about them.2.2.2The dosing session was conducted within a research-dedicated psychiatric inpatient unit. The treatment room itself was modified to be conducive to relaxation. Distracting external environmental stimuli were minimized. During dosing, Daniel laid down on a pull-out couch, with the facilitators seated nearby. Through most of the experience, he wore eyeshades and headphones with music, though he was free to remove them and interact with facilitators at will. The facilitators provided support and guidance when needed.At the start of the dosing session, the facilitators assured Daniel that “anything and everything is welcome” and reminded him of his intention to let himself openly feel and share his emotions. Discussion ensued about his thoughts following the preparatory sessions. He shared an insight that he had been trying to “intellectualize” for a long time and had not fully grasped prior to this time, that “being vulnerable is a recoverable state” .Approximately 90 min after ingestion of psilocybin, the study drug began exerting clear psychological effects. Daniel first reported feeling “spacey” and then entering an “interesting headspace.” He was encouraged to put eyeshades and headphones on and allow the experience to unfold. As his thoughts and emotions began to pick up force, Daniel initially felt resistant to this process due to his strongly learned tendency to push away his feelings. However, at this moment, he recalled being encouraged in preparatory sessions to openly experience whatever might arise during his dosing session. He viewed this prior (and ongoing) guidance to be important in enabling the psychedelic process to unfold.Over a period of about 7 h, Daniel experienced a range of deep and intense emotions. He reported moving into an experience of death where he “went to a place beyond time” in which there was “neither calm nor the absence of calm.” In this experience, he reported feeling his “whole body compost into the ground.” He then reported experiencing a rebirth in which he went “from nothingness into something,” and described “growing back into myself.” This process first involved an experience of growing into a sapling, then a mature tree, living through multiple seasons, and having the ability to be fully present at each moment. After this, he experienced being reborn as a human being. He relived memories, was present with and appreciated each moment and accompanying feelings (both positive and negative), and realized that trying to avoid or suppress feelings could inadvertently lead to greater problems later on. He realized that he had been living as if “chasing perfection was the answer” to “being happy” or “living a life.”At one point during the dosing session, Daniel stated aloud, “This is giving me my life back.” Later on, as the psilocybin's effects wore diminishing, Daniel described the psychedelic experience he'd just been through as the most intense cascade of emotions he had ever felt. Having come through it, he expressed that, however memories or emotions may feel in their quality or intensity, he can experience them and still be okay. He also expressed that he now felt fully opened to his feelings, wanted to share them with others, and was confident in his ability to do so. As he said, “I can carry forward in a way that's acceptable to me. And I think that will be acceptable to others.” He further noted that he had more work and learning ahead and was committed to the process.2.2.3Four integration sessions were conducted by the study facilitators: 48 h, one week, two weeks, and twelve weeks after dosing. Integration sessions were aimed at reinforcing guidance provided in preparatory sessions, consolidating lessons learned in the dosing session, extracting new insights, and incorporating these lessons into daily life. As in preparation, psychoeducation about emotions was provided throughout.Starting with the first integration at 48 h and onward, Daniel reported a new “space” separating him from his OCD symptoms and a changed relationship with them. They now felt “vestigial”, and he was readily able to shift from obsessive thoughts onto other thoughts and behaviors. He described each day as providing new opportunities to dismiss any remaining symptoms and that “making those corrections is not a big deal” with the “distance and perspective” he now had.Daniel described that, prior to the study, a lack of emotional processing of everyday occurrences would lead to “the fallout” that was obsessive thinking. Essentially, instead of processing an event, he described becoming fixated on specific components of events, and then obsessing about those components. However, when he now experiences discomfort from daily events that would have previously triggered that “fallout,” he described instead engaging in a conscious, effortful process of recognizing his feelings, processing them, and moving on. “That's never happened before,” he stated. He also said of the basic experience of emotion, “To use that as constructive input is totally new for me.”He reported long being afraid of whether he and his basic experience of life were “acceptable” and feeling that maybe he was only “safe” because of his long-standing behavioral patterns. During his psychedelic experience, however, he experienced what he described as a collapse down to the very “nucleus” of himself. From this, along with his experience of “being a tree,” he came to appreciate that existence itself is inherently meaningful, and therefore acceptable and worthy of embrace. He also described it as “the linchpin” of enabling him to shift away from his old patterns. Daniel explained, “Having this perspective of having been a different thing completely, and of having been nothing [in that space beyond time] is what… allows me to let go and to say, ‘Okay, that's why this stuff feels vestigial. That's why it feels like a habit in a body and in a brain… and [why I can now] break some of those habits.”He experienced the preparatory sessions and intention-setting for the dosing session as important in providing a mental framework for his psychedelic experience. He also found it critically important that the preparatory sessions had not been narrowly focused on his OCD symptoms but rather on their broader psychological and emotional context. This, along with his perceived safety and comfort with his facilitators, enabled him to be emotionally open and “go to a completely different place.” He expressed a belief that without such careful preparation, he wouldn't have had the same experience and instead might have had a “bad trip.”actually do. This was a novel experience for him. The intensity of his emotions, along with his openness to them, showed him that, as he stated, “I didn't have to be afraid of my experiences and the feelings they evoked. I didn't have to keep running.” He recognized that his history of “compacting” and avoiding feelings prevented him from processing them. Since the dosing session, he was no longer so intently focused on what was “wrong” in his external surroundings. Instead, he now described himself as “re-contextualizing” his feelings and being more aware of and present with them as they occurred. He was accepting of them and expressed an intent to “listen better” to what they might bring. Additionally, Daniel revised his previous feeling of being a “fragile person”, and he now saw himself instead as a “receptive person.” He stated, “I'm not literally a new person, but more in touch with who I am.”The various aspects of his psychedelic experience “informed one another,” he felt, and showed to him that his stated intention to allow himself to feel openly and fully was something he could now 2.2.4In a qualitative interview with an independent evaluator one month after dosing, Daniel reiterated the major insights detailed above regarding his experiences in the preparatory, dosing, and integration sessions. His reporting demonstrated the consistency and durability of these insights. Importantly, he expressed the insight that his OCD arose in part out of non-acceptance of fears in life, which then provided an opportunity for the OCD to “take hold.” He also reported the insight that it was his previous relationship with his thoughts  which was problematic, instead of the contents of his thoughts per se. He described progressively practicing non-judgmental mindful acceptance of his thoughts and emotions as they arose. He also described becoming increasingly able to simply acknowledge that they exist instead of delving deeper into them. He reported that through this approach, he was able to prevent the onset of most, if not all, of his obsessive cascades, thus “reclaiming” more time in his day. He expressed the belief that his experience of “dying” in his psilocybin session was essential for him to develop the ability to accept his obsessive fears. This, he felt, was because he had already confronted one of the deepest human fears, that of death. He also viewed “being a tree” as another “pivotal” moment, one that inspired him to practice “letting go” and be non-judgmental of his negative internal experiences.Overall, Daniel's reported increased cognitive and emotional flexibility seemed to pervade his everyday life one-month post-dosing. He described a more flexible approach to living, in which he attuned to his body more and adjusted accordingly . This was a notable change from before, where he would rigidly follow a set routine as demanded by his OCD symptoms. At the end of the interview, Daniel described associating little to no stigma with having  OCD; he was actively discussing it with his friends, acquaintances, and loved ones, instead of concealing it. He reported hoping that others with OCD will be able to similarly accept that they need help and seek treatment, whether it involves psilocybin therapy or not.3At 12 weeks post-dose, Daniel reported that OCD was no longer a significant part of his life, despite having a persistent “imprint” of obsessions and compulsions in his mind. He felt that if he didn't continue to work at managing this imprint, he could “slip back,” but even if that happened, he now had the “tools” to manage it. Referring to his OCD, he said, “Even if this were to come back, I'm on it.”Daniel's Y-BOCS severity score declined slightly, from 24 to 21, between initial evaluation and baseline, two days prior to dosing; this may reflect increased comfort with the environment and with clinic staff, positive expectations of the dosing session, or simply a shift in focus from his usual preoccupations to the upcoming treatment session. There was a decline in the acute YBOCS , study facilitators were in contact with him regarding this report at one-year post-dosing. Daniel reported having observed, with his wife, the anniversary of his psychedelic experience as his “re-birthday.” He also stated that, “…My world continues to look and feel radically different than it did a year ago. I'm still OCD-free and have a completely new relationship with my emotions.”Between 9 months and 1.5 years post-dosing, Daniel experienced two significantly stressful life events. The first of these events elicited some strong and challenging emotions, but he reported active efforts to acknowledge and accept them rather than avoid them. He was able to recover without great difficulty.The second event was substantially more stressful for him. The aftermath of this event brought about, as he described, a “crushing anxiety” and a recurrence of significant OCD symptoms. He felt “scared” that this might represent “the beginning of a slide” into his pre-study state.He reported that after several days of this, he recognized what was happening and “hit the brakes hard.” For about four days, he dedicated significant time to processing the emotions he felt were stemming from the stressful event. He reported applying lessons learned from both the preparation/integration work with his facilitators and from the psychedelic experience itself. He described allowing his emotions to be present, along with accepting and feeling them without trying to suppress or avoid them. He emphasized that it was “not a cognitive process”. He continued these efforts over a period of about two weeks. As he processed his emotions, he stated, “the anxiety and then the OCD faded.”Daniel remarked that effectively addressing this symptom recurrence highlighted for him that he “still carried the toolkit” of insights and skills he learned from his experience in the psilocybin treatment study. He feels he can apply it at “any time” he needs. He described that the change he experienced through the study “wasn't only a singular transformation” but that the “toolkit” also “provided a sustainable means for ongoing transformation.”In working with Daniel, the facilitators observed his strongly engaged and active efforts from the beginning of preparatory sessions. He reported maintaining consistent efforts to nurture his mental health well-beyond the end of his study participation. Daniel has emphasized that such continual, active effort “is required to sustain” his mental health. He noted also how the facilitators had framed change and good mental health as a long-term process, and that this framing was important to him. As he stated, they “didn't treat it like a light switch, so I didn't treat it like a light switch.”4We have described a case of marked and sustained improvement in a person with longstanding treatment-resistant OCD after a single dose of psilocybin, paired with general psychological guidance and support, and delivered in a controlled setting. This report is consistent with recent findings of sustained improvement after one or two doses of psilocybin in major depressive disorder  and in dOur findings are also consistent with previous case reports and a single open-label trial among individuals with OCD. However, previous case reports have retrospectively described clinical benefit in individuals using illegally acquired Psilocybe mushrooms . Dose anImportantly, psilocybin administration was coupled with a considerable amount of psychological guidance and support – before, during, and after psilocybin administration. While this intervention was not specific to OCD symptomatology, its potential impact on OCD symptoms should not be underestimated. Its importance was explicitly noted, retrospectively, by the patient. An individual's preparation, aims, attitudes, and physical and sociocultural environment (referred to as “set and setting”) may interact with psychedelic effects in influential ways throughout the psychedelic experience . The imp5The past decade has seen renewed interest in the potential of psychedelic medicines to treat psychiatric symptoms and enhance psychological well-being. Our observations in the current case support the possibility that psilocybin-based treatment may be of benefit to some individuals with treatment-resistant OCD.That said, it would be premature to suggest broad use of this treatment strategy, for several reasons. First, while there is optimism that the regulatory environment will change in the coming years, psilocybin and other psychedelics remain Schedule 1 substances in the United States, and are similarly restricted in most other jurisdictions. Their use is complicated by this regulatory landscape and is currently illegal in most contexts outside of the research setting. It is unclear if, how, or when the clinical use of psychedelic compounds outside of restricted research settings will become available. Second, the enormous optimism currently attending the use of psychedelic substances should not obscure how little we know about their optimal deployment, presuming that the field ultimately reaches that point. Questions of dosing (both dosage and frequency) and of the optimal therapeutic accompaniments, as discussed above, remain to be definitively answered and may differ among diagnoses.Finally, the optimal target population for psychedelic treatment is unclear. Importantly, controlled studies such as ours are subject to a high level of regulation and scrutiny, and participants enrolled into such studies may not be representative of the broader population with a particular diagnosis. It has become conventional practice in psilocybin trials to exclude individuals with a history or risk for psychosis, active substance use, polypharmacy, active suicidality, and diagnostic complexity. If and when the regulatory environment relaxes and psilocybin becomes available and appropriate for use outside of heavily regulated research settings, it will be critical to carefully map out the appropriate boundaries of the target clinical population and to be alert and responsive to idiosyncratic needs of particular patient groups .In sum, while our observations in this case are promising, careful further work is needed. Daniel was an early participant in our ongoing double-blinded, randomized placebo-controlled study of psilocybin in individuals with treatment-resistant OCD (NCT03356483). Two other studies of psilocybin treatment in OCD are in their early phases , and others are being planned. We hope that, in the coming years, the role of psilocybin and other psychedelic treatments in patients with OCD will be clarified. We also hope that new treatment options become available for the significant fraction of people with OCD whose symptoms remain refractory to standard treatments.All authors listed have significantly contributed to the investigation, development and writing of this article.Yale Center for Clinical Investigation, grants from the Heffter Foundation and the Turnbull Family Foundation, and by the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center.This work was supported by a grant from Data included in article/supp. material/referenced in article.The authors declare the following conflict of interests:Benjamin Kelmendi is co-founder and Chief Scientific Advisor for Transcend Therapeutics and has consulted for Ceruvia Lifesciences and Lobe Sciences.Christopher Pittenger serves as a consultant for Biohaven, Teva, Lundbeck, Brainsway, Ceruvia Lifesciences, Transcend Pharmaceuticals, Nobilis Therapeutics, and Freedom Biotech, receives royalties and/or honoraria from Oxford University Press and Elsevier, and has filed a patent on the use of neurofeedback in the treatment of anxiety, which is not relevant to the current work.Alexander Belser became Cybin's Chief Clinical Officer during the course of the present study, and subsequently had no further role in the conduct or analysis of the study or in manuscript development. In the last 3 years, A.B. has also received financial compensation for psychedelic research-related activities from MAPS Public Benefit Corporation, Synthesis Institute, Chacruna Institute, and Adelia Therapeutics and has filed patents on the use of psychedelic compounds for the treatment of psychiatric indications.Christopher Pittenger and Benjamin Kelmendi have filed a patent on the use of psilocybin in the treatment of obsessive-compulsive disorder .No additional information is available for this paper.


Interpreting the biomarker values obtained for individual subjects, as estimates of the date of infection, has obvious potential applications in the context of studies of early infection, and has also for some years attracted significant interest as an extra component of post-test counselling and treatment initiation. The applicable analyses have typically run aground on the complexity of the full biomarker growth model, which is in principle a non-linear mixed-effects model of unknown structure, the fitting of which seems infeasible from realistically obtainable data.Testing for ‘recent HIV infection’ is common in surveillance, where only population-level estimates (of incidence) are reported. Typically, ‘recent infection’ is a It is known that to estimate Mean Duration of Recent Infection (MDRI) at a given value of the recent/non-recent -infection discrimination threshold, one may compress the full biomarker growth model into a relation capturing the probability of a recent test result as a function of time t since infection, given a value of assay threshold h which defines the recent/non-recent discrimination. We demonstrate that the derivative (gradient), with respect to h. of the probability of recent infection, seen as a function of both t and h, is identical to the formal likelihood relevant to Bayesian inference of the time since seroconversion, for a subject yielding an assay result h, at or close to the date of their first positive HIV test. This observation bypasses the need for fitting a complex detailed biomarker growth model. Using publicly available data from the CEPHIA collaboration, we calibrated this likelihood function for the Sedia Lag assay, and performed Bayesian inference on hypothetical infection data.We demonstrate the generation of posteriors for infection date, for patients with various delays between their last negative and first positive HIV test, and a range of LAg assay results (ODn) hypothetically obtained on the date of the first positive result.Depending on the last-negative / first-positive interval, there is a range of ODn values that yields posteriors significantly different from the uniform prior one would be left with based merely on interval censoring. Hence, a LAg ODn obtained on the date of, or soon after, diagnosis contains potentially significant information about infection dating. It seems worth analysing other assays with meaningful dynamic range, especially tests already routinely used in primary HIV diagnosis  which have a sufficient dynamic range that corresponds to a clinically meaningful range of times-since-infection that are worth distinguishing from each other. There are many reasons to want to establish timelines of infection and disease progression in patients, across a variety of diseases. In the case of HIV, which is our current application, estimating the time of infectious exposure can assist in further investigations within studies of early pathogenesis, and also support difficult conversations during post-test counselling, which touch on such sensitive matters as where and when one may have become infected, and whom one may have put at risk.It is understood that such estimates, based on laboratory assays, will always be subject to significant uncertainty, most notably from inter subject variability of biological processes, but it seems important to formally assess what is and is not possible, given current biomarkers which provide some sort of calibratable clock for post-infection time. Numerous HIV infection biomarkers of this kind have been identified –4 thoughOne of the few well-known schemes for estimating the stage or timing of infection, usually called the Fiebig staging system, provides for a number of categorical stages post infectious exposure, defined by various combinations of test positivity and test negativity of assays of varying detection sensitivity during early stages of viral replication and immune system response . Most ofRecently, the underlying logic and statistical consistency of the concept of test-discrepancy have been more carefully elucidated by Grebe et al , leadingIn order to go beyond these almost ‘pure interval’ estimates, the most obvious idea is to use the dynamic range of the biomarkers to hand, and to attempt to calibrate some informative dynamic range of values of these markers, to serve as some kind of approximate clock. While, as noted above, there is now increasing use of recent infection testing in clinical contexts, this is still largely based on categorical interpretation using some threshold ,10, the We adopt, according to Grebe et al 2019  and FaceIn the present work, we demonstrate a simple approach, informed by precise formal statistical arguments, to generate continuously variable infection date estimates, when a sufficiently well characterised continuously variable infection marker is available from a test performed at or around the time of first objective evidence of infection.Our investigation is substantially inspired by our work in using markers of infection timing to support surveillance–in particular incidence estimation . As we rIncidence surveillance using markers of ‘recent infection’ is based on the heuristic that a large ‘prevalence’ of a categorically defined ‘recent infection’, among HIV positive respondents in a survey, is an indication of high incidence in a time window preceding the survey.This idea has been made precise by the work of Kassanjee et al 2012 , which dA logically valid recent infection test can essentially be constructed from almost any continuous biomarker with a reasonable dynamic range post infection / initial detectability of infection.recent infection versus non-recent infection):Whether a test for recent infection is usefully statistically informative of HIV incidence depends in considerable detail on many factors, including context, limitations of survey size, etc. but also, crucially, on the two key performance characteristics of the test, understood to be comprised of one or more assays, with rules for dichotomising the net result into Mean Duration of Recent Infection (MDRI) is the mean time which individuals spend exhibiting the ‘recent’ range of the biomarker(s) employed in the test for recent infection [T, which is required to define the upper limit of ‘valid’ recent results–one of several fine points of statistical bookkeeping. The MDRI captures mainly the biology of early pathogenesis, and, in order for the recency test to be truly useful, should not have much variation between contexts.The nfection . There iT, nevertheless are classified as ‘recent’ by the laboratory procedures used to define that [The False Recent Rate (FRR) is the proportion of individuals who, despite being infected for longer than the time cut off ine that . At leasIn this analysis, we use publicly available data for the Sedia LAg assay published as part of Sempa et al 2019 . From thThe CEPHIA Evaluation Panel was tested with the Sedia™ HIV-1 Limiting Antigen Avidity EIA (LAg) assay . The LAgX) of ODn on the assay, given the ‘time since infection’ t, L(X|t). This likelihood function captures all the biological and assay dynamic information that is relevant to our estimation.The goal of this analysis is to quantitatively interpret a specific value of the LAg assay reading , obtained via a standard operating procedure, into an estimate of ‘time since infection’, in a Bayesian framework. For this, we need a likelihood function that expresses the probability (density) of obtaining a particular value  subject to a measurement error (e) distributed according to σ(e|F). The likelihood (density) of observing a value X of the biomarker, at a time t post Date of Detectable Infection (DDI), in an individual assigned the biomarker dynamic parameter vector of importance for the present purposes is formally definable asWe can formally think of assigning each individual, at the time of infection, a vector of parameters L(X|t), which leads toSince we don’t ever know an individual’s parameters F through the calibration of the distribution Obtaining realistic population level biomarker progression functions ection’) .L(X|t) to data.It is also simply not feasible to locate large numbers of individuals who are each known to be infected for some precisely estimable time, and then to observe the distribution of assay results at a healthy selection for these various times–i.e., to directly fit obtaining an assay result below some chosen threshold h.However, we know that it feasible is to estimate ‘Mean Duration of Recent Infection’ (or MDRI) for tests such as the LAg assay used in the present investigation. These estimates have usually relied on the interpretation of a continuous biomarker into a test for ‘recent infection’ by defining ‘recent’ as: t after infection becomes detectable, a subject exhibits a ‘recent’ result, given the assay threshold value h–which in our case simply means that we obtain a biomarker result less than h. In terms of our likelihood defined above:We know from experience in terms of benchmarking  and concBy the fundamental theorem of calculus:PR(t|h) with respect to the recency threshold h. The slight complication is that an execution of the well known fitting procedure intrinsically produces PR(t|h) as function of t, for a given value of h. In order to obtain the derivatives with respect to h, we have implemented a numerical procedure comprised of these steps:So, in order to obtain the required likelihood function, we need merely differentiate Fitting:PR(t|h) functions using a binomial regression with a logit link function, and up to cubic terms in time, which means fitting β0(h) to β3(h) to produce a maximum likelihood fit of:We obtained a family of h, from 0.1 to 4.0, in steps of 0.01.We stored the fitted parameters for values of LAg ODn threshold, Evaluation of Likelihood L(X|t):Pr(t|h) at the target value of t, for the six available values of h nearest to X.We evaluate PR(t|h) as a quadratic polynomial h directionin the .We fit h, of this fitted polynomial, at h = X. This is the likelihood density!We evaluate the derivative, with respect to PR(t|h) is inevitably prone to some fluctuations, it is possible that the numerical derivative with respect to h can be negative, which is unphysical. We only observed this for values of X near the top of the dynamic range of the LAg asay, together with values of t of a small number of days–i.e. situations when it is in any case clear that the likelihood should be neglibibly small, as large assay values are implausible immediately after infection. We implemented a rule of setting the likelihood to 0 whenever the directly obtained value was negative. This had no effect on the salient features of the posteriors.This procedure allows fast and smooth evaluation of the likelihood densities which are required to perform the infection time inference. In some cases, because the fitting of In order to demonstrate the application to infection time inference, we considered hypothetical newly diagnosed individuals with a range of intervals between a last negative and first positive diagnostic test. As previously mentioned, there are subtleties about distinguishing ‘data of infectious exposure’ from the ‘date of detectable infection’ (DDI). We interpret our inference as an EDDI, introduced above, defining ‘detectable infection’ as detectable on the testing algorithm used at the last negative and first positive result. We also assuming, in this first exercise, that there is no connection between infection risk and timing of testing, such as in a study where the timing of testing is imposed by the study protocol. Absent strong information on incidence trends, this leads to a uniform Bayesian ‘prior’ for the EDDI. In this base case, the posteriors are simply the correctly normalised (in the time direction) likelihood densities.In practice, most contexts have patients presenting for testing at date that are to some extent self-selected. In such cases, it is far less clear how one might assign a sensible somewhat informative prior for the EDDI. Various schemes, using epidemiological context, local knowledge about testing behaviours, and additional information gleaned from the patient at the time of testing, could be proposed. This seems to us to be important, going forward, but lies beyond our present scope. We will merely show the application of a somewhat arbitrary non-uniform prior, to indicate that our code handles this case easily enough, and to demonstrate, by comparison to an otherwise equivalent set of test results, how this can affect the inference.Statistical analysis was done using R, version 4.0.2 .Pr(t|h) curves for the LAg assay, out to 600 days, for a range of threshold to define recent infection. At lower ‘recency’ thresholds, the Pr(t|h) curves approach zero convincingly, while for higher ODn values (roughly ODn >2) they clearly do not approach zero.Pr(t|h) curves through a contour plot in deciles. This can be read much as one reads baby growth curves for height and weight, for example. Given a value of time since infection (X axis), a vertical slice through the percentile curves indicates what percentage of subjects’ ODn values lie below the Y values of the contours at the chosen X value. These growth curves are another way one might interpret/present ODn values obtained at the date of first diagnosis. However, this is still a fundamentally frequentist presentation, telling us the probabilities of seeing various values of ODn, given a time since infection, without telling us the probabilities of hypothetical values of time since infection, given an ODn. We find the Bayesian posterior approach significantly more appealing.In Note that not all posteriors have a well-defined mode inside the sensible range of values. This merely captures that for some situations there is no internal ‘most likely’ region for the infection date–it is merely increasingly likely to lie ever further to one side, within the limits sets by the last negative and first positive diagnostic tests.To demonstrate that a uniform prior is by no means essential to our analysis, we present, in Our ‘efficient’ derivation of the likelihood density, which is the crux of infection date estimation procedure, is nothing more than a usually neglected interpretation of constructs which have long been routinely used to estimate MDRI for putative recent infection tests. It does not rely on any special or controversial assumptions. Whether there is sufficient data to estimate this likelihood density without significant parametric artifacts will be a question that must be investigated for any particular biomarker intending to be used in infection timing estimates of the kind we are proposing here. For previously described markers such as the Sedia LAg avidity assay, and numerous others which have been well studied by both an original developer and an independent laboratory –4, it seGiven a particular biomarker, we believe that the fundamental analysis developed here presents the most efficient/informative extraction of infection date posteriors that one can hope for. How useful these estimates are, in practice, will depend on a number of details which we do not claim to be investigating at the present time. In particular:We propose that there be some qualitative investigation into how either the ‘percentile curves’ or the ‘posterior infection date’ estimates can be used in clinical settings, to ascertain how patients and healthcare providers understand and value this information, and hence to propose meaningful guidelines for clinicians to speak about them.Details of biological studies and early intervention trials will determine how significantly more useful the fully developed posterior estimates are, compared to the priors obtained by the post Fiebig interval censoring of Grebe et al 2019  or more Pr(t|h) for various values of h, the computational effort involved in generating these estimates for individual patients is very modest. For further exploration, such as a possible study of utility in a clinical context, we have developed an Rshiny app (https://sempa.shinyapps.io/BM_posteriors_pctcurves/) which requestsGiven that the statistical ‘heavy lifting’ is done once, up front, when fitting the last-negative / first positive test interval, the specification of the diagnostic tests, or their mean ‘diagnostic delays’, andthe specification, and value, of the recency marker obtained at or near the time of first diagnosisand, from this information, generates the infection date posterior. Further, we are in the process of expanding it to include other recency like Maxim LAg, bio-rad Geenius, Abort Architect and some annotation like specific percentile ranges, and to cater for at least sigmoidal informative priors specified by 4 parameters .Despite the hesitancy in some quarters about using recent infection tests for individual level rather than population level testing , we noteS1 File(CSV)Click here for additional data file.