In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as to make the concept of exhaustion genuinely operational. In this essay, we have written a critical review on immunological exhaustion. We believe that this widely used concept often remains in fact imprecise because there exist 3 different approaches to exhaustion, namely, in terms of dysfunction, cause, and marker, and those are not sufficiently well distinguished and articulated in most scientific papers. We also propose to talk about “exhaustion” for and only for the phenomena in which all 3 approaches are aligned. This can be called the “convergence strategy”: T cells would be described as “exhausted” if and only if they are simultaneously dysfunctional, express given markers such as programmed cell death protein 1 (PD-1), and induced by a specific cause such as chronicity. This strategy could be perfectly reasonable, and we see much value in adopting it, because it would force everyone to be more specific and rigorous when talking about exhaustion. Clarifying the characteristics of cells defined as “exhausted,” and using a convergent strategy to define T-cell exhaustion could have major experimental and clinical consequences, including for viral infections such as the Coronavirus Disease 2019 (COVID-19). Despite previous mentions to “exhaustion” in the immunological literature ,2, the fFig 1). The first approach primarily defines as exhausted the cells that present the same cellular dysfunction . The second approach primarily defines as exhausted the cells that are produced by a given cause . Finally, the third approach primarily defines as exhausted the cells that present the same molecular markers . One difficulty is that authors tend to overlook specifying which approach they have in mind when they qualify cells as “exhausted.” A second even more serious difficulty is that authors often act as if these 3 approaches necessarily aligned , when in fact they don’t. As we will see, even the seemingly consensual view that antigen chronicity is the leading cause of exhaustion is questionable, including in the historically paradigmatic LCMV example. More recently, a subset of stem-like CD8+ T cells has been identified among exhausted T cells and presented as a much more rigorous characterization of exhaustion, but, as we will see, the nonoverlap problem also applies to this subset [In subsequent research until present day, 3 approaches to immunological exhaustion have coexisted, with often unclear connections  they have in mind, we will try to present as precisely as possible these 3 approaches.Originally, exhausted T cells were understood as dysfunctional. What is meant by “dysfunction” here is that some T cells, after activation and proliferation, do not fulfill the functions they are expected to perform as effector T cells—typically, they fail to eliminate infected cells and control the virus. As originally described, antigen-specific T cells become “dysfunctional” during the chronic phase of high viral load infections, with progressive loss of interleukin (IL)-2, then tumor necrosis factor alpha (TNFα), and, finally, interferon gamma (IFNγ). Authors have called these cells “dysfunctional” because they compare their functions in the context of a high-dose persistent chronic viral infection with the functions of the same cells in the context of acute viral infection when the virus is cleared .In the original sense of “exhaustion” and especially for Zinkernagel’s team, the dysfunction that is characteristic of exhaustion can be defined independently of any cause or marker. Exhaustion is understood as the non-elimination of the virus due to the peripheral deletion of virus-specific cells. This constitutes a genuine functional characterization of exhaustion. Within this approach, saying that the cause of exhaustion is the exposure to high doses of a chronic antigen is therefore not circular: This cause is offered as the best possible explanation for an independently defined phenomenon.The dysfunction associated with exhaustion has often been conceived in contrast to another dysfunctional state, namely “anergy.” The consensus is that anergy results from an absence of signal 2, and, therefore, a failure to become activated, while exhaustion occurs after T cells have been fully activated and have proliferated –14.+CD8+ T cells resemble stem cells during chronic LCMV infection, undergoing self-renewal and also differentiating into the terminally exhausted CD8+ T cells [It is important to characterize as precisely as possible the nature of the dysfunction thought to be characteristic of exhaustion. For example, although this dysfunction has sometimes been conceived as involving an incapacity for maintenance and expansion –17, some T cells . However T cells .“Exhausted” cells transferred into a naive host can reexpand and protect it against the same pathogenic challenge , suggestIs exhaustion always dysfunctional? There are important disagreements on this issue, some authors considering that exhaustion is by definition dysfunctional, while for others, exhaustion could be functional in some contexts ,23,24. OA second major approach is to say that exhausted cells are cells that are produced by a particular cause, typically antigenic chronicity and/or high antigen load. In the original LCMV model ,5, both 6), as opposed to a low dose of the same virus (102), leads to exhausted cells by day 8 [In subsequent work, antigenic chronicity remained an often mentioned typical cause leading to exhaustion ,27. Natuby day 8 , suggestA second cause said to trigger exhaustion is indeed high antigen load. As previously said about the historical LCMV model, the claim that T cells were exhausted in C-13 by contrast to the Armstrong strain was based on the fact that the viral load was both higher and chronic ,21. The Fig 2). One such additional cause is the cytokine environment, with a typical focus on IL-10 and TGF-β (which tend to favor exhaustion) [Importantly, other causes of exhaustion, beyond chronicity and antigen load, have been suggested, including contextual causes (austion) ,33,34 asaustion) . Incidenaustion) ,37 and maustion) .According to the third approach, exhaustion is the cell state associated with the expression of particular molecular markers—classically inhibitory receptors. Because there are many of them, only the most discussed in the scientific literature are mentioned here.PD-1 has been the most extensively studied marker of exhaustion. It is considered as characterizing exhausted T cells in both chronic infection and cancer and associated with dysfunction in both cases ,40. In aex subset” [Some transcription factors have been interpreted as favoring exhaustion, for example, B lymphocyte–induced maturation protein 1 (Blimp-1), Eomesodermin (Eomes), Tox, and IRF4 (reviewed in ). During subset” . Tox has subset” . Moreove subset” . IRF4 co subset” ,43,44.Finally, exhausted cells display metabolic changes such as inhibition of aerobic glycolysis due to glucose transport limitation and consumption by cancer cells, mitochondrial dysfunction, and oxygen deprivation , which, Listeria monocytogenes [A common attitude is to assume that the 3 approaches to exhaustion generally align: Dysfunction would be produced by well-identified causes such as chronicity and/or high antigen load, and it would be associated with the expression of well-identified markers such as PD-1. In reality, though, these 3 approaches often fail to overlap. A lot of data suggests that exhaustion in the functional sense does not always causally result from antigen chronicity. Exhausted T cells have been described in chronic infection with LCMV, HIV , hepatitytogenes , and HBVytogenes . In a nuytogenes ,50, and ytogenes . In otheytogenes ,51, or dytogenes , there iAnother significant (and related) challenge is that exhaustion in the functional sense is not always caused by exposure to high doses of antigen. It has been recently shown that, in different infections, the adoption of an “exhausted” dysfunctional phenotype by antigen-specific CD8+ T cells occurred before the viral outcomes diverged, suggesting that viral load was not a primary driver of differential expression .Regarding the markers used to define exhaustion, lack of overlap can also be observed. First, although PD-1 is the most often mentioned inhibitory receptor associated with exhausted T cells, it is certainly not a specific marker of exhaustion, as it is expressed after acute TCR activation . The expTranscription factors also have ambivalent roles depending on the context. For example, Eomes has been associated with exhaustion during the chronic phase of infection, but it is up-regulated during acute infection, favoring effector molecule production (IFNγ), IL-15Rβ, and memory development ,62. Tox IRF4 has been described both in LCMV infection and in allotransplantation, with a potential dual role. It shows a pro-exhaustion role during LCMV and cancer. In contrast, the deletion of IRF4 in CD4 T cells resulted in dysfunction and graft tolerance, which means that, when expressed, IRF4 represses PD-1 and Helios  and favoFinally, the metabolic changes observed in exhausted T cells can also occur in the tumor microenvironment through causes distinct from antigen chronicity and high antigen load .The upshot is that, despite the frequent tendency to consider the 3 approaches to immunological exhaustion to be aligned, it is often not the case. Some situations instantiate “exhaustion” from the functional viewpoint but are not associated with the classic molecular markers of exhaustion and/or the classic causes of exhaustion. This absence of convergence between the 3 approaches can be extremely problematic, as we can illustrate it now with the examples of cancer and Coronavirus Disease 2019 (COVID-19).The fact that the 3 approaches to exhaustion do not always conceptually overlap can generate significant issues at the experimental and clinical levels.The application of the notion of “exhausted T cells” to cancer is particularly telling. The aim of cancer therapies based on immune checkpoint inhibitors is to target dysfunctional T cells in cancer by reversing their state of tolerance to the tumor ,67. In rFig 3). Acting as if the 3 approaches always overlapped in cancer would be inappropriate and misleading, as (1) there are cases of cancer where some markers of exhaustion are dissociated from the causes of high antigen load and chronicity [The claim that targeting dysfunctional T cells in cancer is equivalent to targeting exhausted T cells is, however, problematic for at least 2 fundamental reasons. First, for the clinician, targeting “exhausted T cells” will have a very different meaning depending on whether what is targeted is the dysfunction itself, the underlying causes, or the markers of exhaustion  dysronicity ; and, coronicity ,77. ThisCrucially, even when focusing on one specific and explicitly described approach to exhaustion, many important difficulties remain. This can be illustrated with the application to cancer of the causal approach of exhaustion. The main suggestion in papers linking cancer and exhaustion has been that the causes characterizing exhaustion in the viral context would also occur in cancer: The chronic exposure of T cells to a high load of tumor antigens would lead to their exhaustion, and, therefore, to the incapacity of these T cells to control tumor growth. This idea led to the hypothesis that poor immune responses to cancer are related to chronic exposure to high levels of tumor “neoantigens” ,79 , focusing on exhaustion remains problematic because it constitutes at best a small subset of the many forms of immunological tolerance to the tumor. There are, in fact, many parameters that help explain the elimination or non-elimination of the tumor by T cells, and each of these parameters can be linked to biomarkers—as suggested by the concept of the “cancer immunogram” . FurtherFig 4 sums up examples of nonoverlap between the 3 approaches to exhaustion.Recent work on COVID-19 offers another interesting example of the potential inconsistencies and misunderstandings that can be associated with the concept of exhaustion. CD8+ T cells present an exhausted phenotype in many COVID-19 patients, but the cause involved is not always mentioned . High anFrom the 1990s to the present day, many immunologists have suggested that exhaustion might in fact reflect an evolutionary conserved process of immunoregulation ,11, limiOne important way to approach this question is to adopt a multilevel perspective. A process that seems dysfunctional at a lower level can in fact be part of a functional regulatory process at a higher level. Typically, a state of exhaustion might be dysfunctional at the cell level while being functional at the tissue or organism level—for instance, if exhaustion helps limit immunopathology. This approach is convergent with a role for exhaustion in the phenomenon of “disease tolerance.” Disease tolerance, a term long used in plant ecology  and refeThe perspective presented in this paper opens up original and promising avenues for future research in at least 3 areas:Regulation to self: Future work needs to determine whether immune responses to “self” display some characteristics generally associated with exhaustion . Recent research has started to explore the role of exhaustion in the prevention of autoimmune diseases [diseases ,98, but Regulation to “resident nonself”: Typically, the microbiota. Studies on the microbiota do not even examine the phenomenon of immunological exhaustion. An intriguing hypothesis would be that the experimental inhibition of exhaustion in the gut or on the skin might lead to elimination of some microbes with which the host normally cohabits.Negative consequences of excessive limitation of exhaustion in contexts of the following:(a) Infection: Although limiting exhaustion in some contexts of viral infection is a legitimate objective, we expect that an excessive inhibition of exhaustion could lead to pathological consequences, from immunopathology to the development of autoimmune disorders. The idea of an equilibrium between beneficial and detrimental exhaustion has been present for a long time in the literature on exhaustion and has been specifically investigated in recent times, but what is needed now is an explicit description of the causes that will insure an adequate equilibrium.(b) Cancer: There is no doubt that reversing T-cell exhaustion in some cancers can be useful. Yet, as we have seen, the sense given to the “exhaustion” of these cells is not consistently clear, and, in many cases, restoring the functions of these cells does not really amount to suppressing their state of “exhaustion.” Moreover, future research will certainly confirm that the “reinvigoration” of T cells in cancer may lead to detrimental consequences for the host in terms of immunopathology and autoimmune responses, which makes it all the more important to, first, specifically understand the type of immunoregulation (not necessarily reducible to exhaustion) involved in immune responses to cancer, and, second, systematically understand the causes of T-cell responses to cancer in the broader context of the many components of the immunological tumor microenvironment.(c) Allergies: Allergies are another domain in which, interestingly, exhaustion is almost never investigated. Future studies will have to determine if exhaustion plays a role in the allergic response, and, possibly, in desensitization (where the antigen is chronic but present in low quantities).Discussing the definition of “exhaustion” is not just a matter of words. It has crucial consequences in experimental and clinical practice.


This article examines why older people were particularly prone to suicide in Georgian England, and argues that their suicidality is best understood through the lens of the ‘ageing body’. By centring on the experiences of the suicidal, it proposes that suicide was not ‘medicalised’ in the way traditionally described in the historiography, being reconceptualised, over the course of the eighteenth century, as a product of lunacy. Instead, it contends that older people often thought that their suicides were a rational response to the struggles of ageing, which included physical decline and embodied memory-loss. To do this, it uses previously unseen coroners’ inquests from across England, in addition to wills and medical writings. It examines these inquests for what they can tell us about the emotional and embodied experiences of older suicidal people, thus contributing to an under-researched aspect of the social history of ageing. On one August morning in 1795, Edward Hearne hanged himself in his bedroom. As his wife explained at his inquest, he had been ‘melancholy and Dull’ for some time, mostly on account of his age and infirmity—he was, indeed, aged 74, with disturbed eye-sight and a wavering memory. Due to his age and frailty, Hearne began to withdraw from his formerly independent, active life as an upholsterer, and he ‘often Complained & sayed being an old man he was afraid him & [his wife] would come to want as he was not so able as he used to be to work & get his living’.Sleepless Souls, Michael Macdonald and Terence Murphy devoted no more than nine pages to discussing age demographics, while R. A. Houston gave age only the most fleeting notice in Punishing the Dead.Although Victor Bailey has used the lifecycle as a key framework for understanding Victorian ‘self-murder’, no historian has built on his insights to give age the attention and analytical importance it deserves in their studies of pre-Victorian suicide.A guide to health (1744) stated, ‘the fiftieth year’ is ‘where Old Age begins’.As indicated, I will here be defining ‘older’ people as those aged 50 and above. Certainly, there was no ‘universal threshold of old age’, and people could pass into the final stages of the lifecycle at many different points, depending on a range of corporeal and social factors.non compos mentis verdicts increased over the early modern period, and their argument, that this was due to the medicalisation and secularisation of suicide—were all products of their keen focus on ‘changes in attitudes and responses’ to suicide.Sleepless Souls, similarly concentrated not on the ‘meaning of suicide’ to ‘the people who die’, but on ‘the attitudes and behaviour of those who interact with the self‐murderer after death’.non compos mentis. However, this is not how many suicidal people viewed themselves; for them, suicide could be a logical and rational choice. Macdonald and Murphy have, therefore, only told us one side of the story.These age-related difficulties were very often linked to older people’s suicidality.By focusing on the struggles of older suicidal individuals, this article contributes not only to histories of suicide, but histories of age and ageing. For although scholars such as Susannah Ottaway, Pat Thane and Lynn Botelho have thoughtfully examined many experiences of ageing and agedness, ‘old-age mental disorders and old-age emotional worlds still constitute an unexplored field’.This article is based upon a sample of 106 inquests (with depositions) into the suicides of older people, found in archives in Maidstone, Whitehaven, Chelmsford, Ipswich, Norwich, Bath, Middlesex, Westminster and the City of London.exact textual replicas of the verbal back-and-forths between the coroner, witnesses and jurors. The coroner’s and jurors’ questions were never recorded—though it is often clear what they were. Although they were guided by the questions, witnesses had the freedom to disclose a wide variety of details about the deceased, and often sought to report, verbatim, words or phrases the deceased had used, often documented in speech marks. Overall, depositions offer us fruitful evidence of how people acted and felt before their deaths, most especially in suicide cases, where legal significance was placed on someone’s mental state. Partly for this reason, this evidence presents some problems. Since suicide was illegal, depositions were not only used to ascertain why someone died, but whether the person was a felo de se—a rational individual liable for punishment—or non compos mentis. Therefore, most deposers, often having been close to the deceased, stressed their mental affliction. However, by and after the 1770s—the time from which most of our inquests come—well over ninety per cent of suicides were decreed non compos mentis, even on tentative accounts of mild distress.persuade a coroner of mental affliction was minimal.As Tim Hitchcock, Sharon Howard and Robert Shoemaker contend, depositions were recorded in ‘a form that was near to the actual words spoken’ by witnesses.Furthermore, the legalistic necessity to highlight distress does not negate its existence. Within one inquest, there are often many detailed and cross-corroborated reports of a person’s behaviour and words. These second-hand accounts offer us unrivalled insight into older—and mostly poor and illiterate—suicidal people’s struggles and emotions. Within this sample, of the ninety-two people with identifiable occupational or social status, 61 per cent were lower-class, 28 per cent were of middling status, and 11 per cent were upper-class.Undoubtedly, these experiences are refracted through the voices of others, and their views—about suicide, about ‘sanity’, about relationships—are also captured in the sources, and are present in this article. However, just as, in the present day, ‘psychological autopsies’  are valued for offering ‘retrospective information’ on the ‘process of suicide’ for an individual, eighteenth-century coroners’ inquests can help us explore suicidal experiences in another era, particularly when explored collectively, and complimented with other lines of evidence .In exploring them, this article also builds upon the wider historiography of emotions which, as Rob Boddice notes, is embedded within research into ‘experience’.This article will first explore emotional responses to experiences of physical decline and deterioration. Secondly, it will examine issues around embodied memory-loss. Thirdly, it will consider feelings of burdensomeness, particularly anxieties about being a burden, and ideas about the burdensomeness of life itself. Lastly, it will look at the notion of being a withdrawn or withdrawing presence, and discuss aloneness and communication difficulties. Of course, these themes were often overlapping and interrelated, as shown in Overall, this article will argue that older people’s preponderance towards suicide in this period is best understood through the lens of the ageing body. It will show that, by repositioning our attention on the lives of the suicidal, rather than upon the views of those who outlived them, a more complex history of ideas about mental health emerges. While some older people felt mentally unwell before their suicides, others saw their self-inflicted deaths as a rational response to the struggles of pain, deterioration and dependency in old age.A sermon against self-murder (1708), Knagg declared that it was always wrong to kill oneself, even if our ‘many Years’ are rendered ‘irksome and tedious by reason of the many miseries Old Age exposeth us to’, such as ‘the Stone’ and ‘the Gout’.In Thomas Knagg’s These worries were clearly articulated by Thomas Browne, a 60-year-old man who hanged himself in Saffron Walden in 1802. The day before he died, he complained to a neighbour that ‘he was not the man he had been, meaning … that age and Infirmity had reduced him’; he even believed—to the confusion of his neighbours—‘that he had got no Legs’, a delusion which potentially expressed anxieties about his ailing body. As one neighbour explained, he saw Browne:them for he was going soon either to Heaven or Hell but Hell he expected.look wistfully at him, [so he] asked him whether he had got the ague … he said, no, he had lost his legs, he had got no Legs, & this deponent says that he shortly afterwards said to the best of his Recollection, that he should not want Browne’s legs seemed to ground him in the living world, with Browne determining that his ‘lost’ legs would not be needed in the afterlife. He apparently located a sense of death’s inevitability in his declining capacity to walk and work as a labourer. A neighbour explained that, when he came to her house equipped with a shovel, she had asked him where he was going, to which ‘he said “ you will never see me any more” & she asked him whether he was going on the Tramp [i.e. walking about searching for work] & he said he would never go upon the Tramp any more’.In his study of physical disability, David Turner notes that work played ‘a direct role in establishing men’s identity’. Older suicidal people often expressed such feelings about the irreversible direction of bodily decline, and its relation to dependency and degradation. William Richmond, an ‘old Carpenter’ who hanged himself in Westminster in 1790, was deeply affected by his dwindling bodily powers and what they represented. He had ‘become Ill and Lame’ and was accordingly ‘in want’, encumbered with a body that no longer ‘worked’, in multiple senses of the word.The anxiety and debasement that late-life unemployment could bring were also clearly articulated by Thomas Emperor, an older ‘under Porter’ who was found drowned in 1799. Despite copious evidence of mental distress, the verdict was unusually given as ‘death by misfortune’, probably because Emperor worked for the Prince of Wales at Carleton House, and it was necessary to avoid a scandal.he should be turned out of his place and that then he should die in a Ditch like a Dog and be buried in a Ditch like a Dog … the deced soon after sayed there pointing to a Corner of the Room there is his highness and major Lee talking about me I am sure I shall be turned out of my place.The striking language and debased imagery of dying ‘in a Ditch like a Dog’—which, being repeated, was possibly Emperor’s phrase—indicates feelings of animal-like degradation and corporeal helplessness. It is worth noting that the decade within which the largest number of suicides occurred (over a quarter) was the 1790s, a time of considerable economic distress and employment vulnerability, which would have been particularly difficult for older people.Notes of Me, written around the turn of the eighteenth century. As he mused, when men are ‘desperate in health … as in [the] case of wretched old age … so that death is certain, but the time uncertain, only the acute pains and comfortless condition in the interim infallible … I admire that any man in such condition should desire to live, or indeed should not court death’, or even ‘wilfully procure it’.As Hannah Newton notes, the weakness and decrepitude of old age were thought to present hindrances to recovery from illnesses and physical problems; Daniel Schäfer even argues that old age was pathologised as a unidirectional ‘state of illness’ in the eighteenth century.The relationship between bodily deterioration and emotional or mental suffering was not unidirectional, with a ‘mind’ responding to a declining body. Minds are always embodied, and old-age somatic decline affected memory and cognizance in distressing ways. Older suicidal people were particularly likely to be affected by memory-loss, which is mentioned in 19 per cent of the 106 cases examined here, compared with 4 per cent of cases in the general sample.Take the case of John Braithwaite, an elderly gentleman who drowned himself near Egremont in 1803. Braithwaite was so frail that he asked one of his servants to kill him. As she deposed, he ‘complained much of uneasiness and being afflicted and sayd there must be an End’, and ‘asked her if she wd. put an End to him—He sayd he cd. not do it himself’.Observations on Man taught, in cases of old-age dotage:In the inquest, we can thus see how those around Braithwaite observed his deterioration, identifying embodied memory-loss as crucially important to his demise. Note how Jackson located Braithwaite’s problems in a declining ‘brain’; as physician David Hartley’s 1801 edition of the brain itself [is] in a languishing state … we see, in old persons, all the parts, even the bones themselves, waste, and grow less. Why may not this happen to the brain … to destroy the powers of association and memory?.Schäfer has argued that, after 1700, medical writers increasingly ‘somaticised’ memory-loss—that is, located its cause in somatic decline and linked it to old age—a trend that might explain Jackson’s discussion of cerebral deterioration. In the depositions we also, however, get a sense of Braithwaite’s own emotional response to his memory-loss. He articulated his anguish to his servant, saying that ‘he thought it hard that the Almighty shd. afflict him in that manner’, and to his surgeon, ‘complain[ing] that his situation was dreadful and Death wd. be a Blessing to him’.A wavering memory thus lessened elders’ independence and ability to function within their communities. Nevertheless, Jesse Cook, an ailing older man who lived in rural Suffolk, tried, like Braithwaite, to behave ‘normally’ as before. Repeatedly, Cook set out for one familiar destination, but ended up at another, as he ‘turned into the fields, lost himself’ and resurfaced late at night. When he went to fetch water, his housekeeper, becoming nervous that he might ‘tumble, or throw himself into the well’ tried to help him, but he ‘would not let her’, indicating that Cook felt aggrieved at his lessening independence.As with Cook, confusion and memory-loss could disrupt older people’s sense of place, both geographically and temporally. James Barkley, who hanged himself in his cellar in 1776, became disorientated in the years before his death, often commenting to his friend that ‘he cod. not tell whether he was at Arkill's  or at home’.Of Suicide (1777), in which Hume declared that when ‘age, sickness, or misfortune may render life a burthen, and make it worse even than annihilation’, suicide is ‘consistent with … our duty to ourselves’.In advancing years, physical and mental ill-health took a toll on people’s sense of personhood. There is an impression, in the sources, that a life encumbered with age could itself be regarded as a burden. This idea was explicitly suggested in David Hume’s controversial Indeed, the physical and financial care that older people often needed could make them feel ashamed and anxious. The case of James Dowdle, who cut his throat in Bath in 1803, encapsulates this. Dowdle had been committed to gaol, but was still being cared for by his daughter, who ‘went up to her father’s room to take away his breakfast things and his dirty linen when to her great astonishment and surprise she saw him lying on the side of his bed’.noise and unquietness among strangers’.Of course, not all older people could be cared for by family members, and some consequently faced different feelings of rejection or despondency. Sarah Fenwick had been residing with her adult daughter since her husband died four months before, but, as her daughter testified, she ‘several times told her Mother that her Family was large and ha[d] perswaded her to go into the Workhouse’.Most suicidal people thus viewed the workhouse as a wretched and even shameful place to spend one’s old age. This is suggested in the inquest of Thomas Coe, a 73-year-old man who killed himself in Saffron Walden in 1804. In the moments before he hanged himself, Coe—who was confined in the workhouse ‘Bridewell’—was interrupted by the workhouse tailor who, being threatened by Coe, ran off for assistance (which came too late). Before he ran off, the tailor had, however, observed Coe get ‘upon his Feet’ and say ‘he was ashamed of his Life and to live’, which were seemingly his last words.reduced him’, there was a sense that older people were shrunken, weighed down, dried out and diminished.Suicidal older people sometimes utilised, more explicitly, discourses around burdensomeness and the ‘bearing’ of loads. Before she killed herself in Maidstone in 1779, Phillis Jury rather cryptically expressed to her neighbour that ‘her Burthen was too great to bear’ and, on being asked why she had taken poison, replied that ‘she was tired of life’, ideas of downtroddeness and exhaustion connoted in both statements. Similarly, Ann Tiffin ‘Complained heavily of the Burthen she had upon her Mind’—a feeling that she ‘could never be happy in this world since the Death of her Husband’—as if her grief was a weight pulling down upon her.It is within this context of corporeal and social problems that we turn to the issue of older suicidal people’s withdrawal from aspects of family or community life. Ottaway has argued that, though it was acceptable for  elders to ‘withdraw from their life’s work’, overall, older people remained active participants in their communities.become, as it were, Children a second time’.Part of this withdrawal of presence arose from ‘regressions’ in behaviour, which made it difficult for others to understand older people. It was a common trope that the elderly entered a ‘second infancy’; as George Cheyne wrote, ‘old Men … The withdrawal of communication is significant in itself, and some elders seem to have made a more conscious effort towards it. Before her death, Elizabeth Sharp, an older woman who killed herself in London in 1813, stopped engaging with her family, ‘refusing to see any visitors & if accosted on the stairs … would return no answer’.Some elders had a rather different relationship with solitude, and were afraid of being alone. This fear was still, however, connected with a reduced or withdrawn presence, in the sense that it often stemmed from feelings of physical and social vulnerability. While some historians—such as Keith Snell and Fay Bound Alberti—have paid increased attention to the historical issue of loneliness, few have discussed this connection between fear and aloneness in the vulnerable.The Age and Life of Man (c.1800) had it:Some of this fear seemingly stemmed from older people’s concerns about what they might do to themselves. Indeed, while I have shown that many older people saw their suicides as a rational response to the problems of agedness, there were also some cases in which older suicidal people felt mentally unwell, and were afraid of their own capabilities. Elizabeth Hughes, who had been ‘Infirm in body’ for a few years, had told her nurse that she was troubled by ‘very bad thoughts and was afraid of being alone’, while Margarett Leverett, a 55-year-old woman who killed herself in Saffron Walden in 1783, was similarly ‘afraid to be left alone’.Then Man appears fifty five years,And sick both Ev’n and Morn:Loins, Legs and Thighs with sore Disease,Make him to Sigh and say,Ah! Christ on High have mind of me,And Learn me for to die.’Indeed, in their agedness, older suicidal people certainly thought about the proximity of death, as in the case of Browne, discussed above, who said ‘he would not hop into a Coffin (i.e. kill himself) but God knows how soon he may be laid in one’.It is surprising that scholars have not examined, in any depth, the reasons why older people were ‘unusually suicidal’ in this period.This article has aimed to show that coroner’s inquests provide a ‘way into’ examining the suicidal experiences which have been so long ignored by the traditional historiography. In the absence of other sources, the depositions of friends, families, neighbours and medical practitioners provide rich evidence of the behaviour, words and feelings of the ‘voiceless’ dead. Though not an unproblematic source, they clearly document complex and visceral feelings of distress, anger, fear, debasement, pain and despair, providing rich scope for emotions-history research which puts emotional actors at the centre of its narratives.This work was supported by the Arts and Humanities Research Council [grant number AH/L503897/1]; The Wolfson Foundation  and the Social History Society Conference Bursary.


Many of the world’s most pressing issues, such as the emergence of zoonotic diseases, can only be addressed through interdisciplinary research. However, the findings of interdisciplinary research are susceptible to miscommunication among both professional and non-professional audiences due to differences in training, language, experience, and understanding. Such miscommunication contributes to the misunderstanding of key concepts or processes and hinders the development of effective research agendas and public policy. These misunderstandings can also provoke unnecessary fear in the public and have devastating effects for wildlife conservation. For example, inaccurate communication and subsequent misunderstanding of the potential associations between certain bats and zoonoses has led to persecution of diverse bats worldwide and even government calls to cull them. Here, we identify four types of miscommunication driven by the use of terminology regarding bats and the emergence of zoonotic diseases that we have categorized based on their root causes: (1) incorrect or overly broad use of terms; (2) terms that have unstable usage within a discipline, or different usages among disciplines; (3) terms that are used correctly but spark incorrect inferences about biological processes or significance in the audience; (4) incorrect inference drawn from the evidence presented. We illustrate each type of miscommunication with commonly misused or misinterpreted terms, providing a definition, caveats and common misconceptions, and suggest alternatives as appropriate. While we focus on terms specific to bats and disease ecology, we present a more general framework for addressing miscommunication that can be applied to other topics and disciplines to facilitate more effective research, problem-solving, and public policy. Effectively communicating complex scientific findings to diverse professional audiences, as well as policy makers and the public, can be very challenging. Yet, failure to do so results in misperceptions and misunderstandings that can hamper the progress of science and have significant consequences for the development of public policy. Zoonoses are diseases that originate in animals, either wild or domestic. Zoonotic diseases, especially those from wildlife, garner great attention from policy makers and the wider public because of their impacts on global public health and biodiversity conservation. As the emergence of SARS-CoV-2 from an unknown reservoir leading to the COVID-19 pandemic highlights, effective communication is central to all levels of response, from understanding the origins and evolution of the pathogen to developing policies that can mitigate its spread in human populations. However, communication is challenging because understanding the ecology and emergence of these diseases requires interdisciplinary research, including for example wildlife biologists, ecologists, virologists, microbiologists, evolutionary biologists, and epidemiologists, among others [Bats are an order of mammals encompassing over 1400 species that vary greatly in their life history and ecology . RecentlEffective communication relies on intentional transmission by the sender of unambiguous messages that are received and understood by the target audience . Over tiIncorrect or overly broad use of terms—words in which the sender is unaware of the accepted definition of a term in the field(s) that coined it and so uses the term erroneously, or without the level of evidence that would support that use, e.g., bats as the reservoir of MERS-CoV or SARS-CoV-2. This perpetuates misinformation and misunderstanding in audiences, whether they are other researchers or the general public.unstable usage within a discipline , or different usages among disciplines , leading to confusion or misunderstanding in audiences.Terms that have incorrect inferences about biological processes or significance in the audience .Terms that are used correctly but spark Incorrect inference from the evidence presented. This may be due to the fact that the audience  is unfamiliar with the methodologies generating the evidence .In communication about zoonotic diseases and bats we identified four recurrent types of miscommunication that are profoundly impacting inference and thereby interdisciplinary communication, public opinion, and, potentially, policy . They arWe note that some terms  may be misused in multiple ways that can fall into more than one category.Here we present a short glossary of terms that illustrate these four types of miscommunication that we believe have caused the most confusion and disruption to effective, accurate communication regarding zoonotic diseases and bats. We have organized the presentation of these terms into four broad groups: actors or entities, such as “pathogen” or “reservoir”; processes or events, such as “spillover” or “spillback”; descriptors, such as “endemic” or “novel”; methodologies, such as “serology” or “phylogeny.” For each term, we note which problem type(s) it falls under and provide a definition, examples of correct use, and an overview of common misconceptions, misuse, and caveats. We recommend alternatives where appropriate. While we have focused on terms that we find have been commonly misused with regard to bats during the COVID-19 pandemic, misuse of these terms and the types of miscommunication that they exemplify are also applicable to other species, situations, and disciplines.a. Entities(i.) Pathogen (Type 1)Definition: A pathogen is a microbe that either causes damage in a susceptible host or has the potential to do so [Plasmodium. While pathogenicity, the ability of a microbe to cause damage to a host, was originally conceptualized as intrinsic to the microbe, it has become increasingly clear that damage is due to the interaction between a microbe and a specific host, and may be caused by the pathogen , the host immunological response , or a combination of both [Rickettsia species within the spotted fever group to humans has recently been attributed to the different ways in which these very similar bacterial species manipulate host cell function [to do so ,15,16. T of both ,15. Thus of both . For exa of both . Similarfunction . It is ifunction . In addifunction .Appropriate use: The term “pathogen” should be used to describe microbes that cause damage or disease in a host. Whenever “pathogen” is used, the host species in which the microbe may cause damage should be specified.Caveats and common misconceptions or misuse: “Pathogen” is sometimes used loosely as a catch-all term to describe microbes that have been isolated or detected in samples, without determining whether they cause damage or disease in hosts  or speceproduce , may be eproduce ,23,24). eproduce , especiaRhinolophus shameli in 2010 in Cambodia with 92.6% similarity to SARS-CoV-2. While the authors clearly note that, “further risk assessment is needed to understand the host range (including humans) and pathogenesis associated with this novel sublineage”  sineage”  Reservoir or Reservoir Host (Type 1)Definition: A reservoir is a population, species or community (assemblage of different species in a given geographic area) in which a microorganism naturally occurs and is indefinitely maintained [intained ,30. Someintained . Microorintained . A pathointained , in partLycaon pictus) are a target species for rabies spillover from domestic dogs (Canis lupus familiaris) [Lyssavirus, was first isolated from the leaf-nosed bat Hipposideros commersoni in 2009 [H. commersoni or other bat species are its reservoir, the population in which the virus is maintained [H. commersoni group has been reassigned to the genus Macronycteris [M. gigas or M. vittatus). This knowledge is important for understanding the ecology and dynamics of Shimoni virus even if spillover to other target populations does not occur, and it will be essential if it does. This underscores the point that a population would have to serve as a reservoir in which a microbe circulates prior to spillover to a target population. For example, dromedary camels (Camelus dromedarius) appear to have been a reservoir for MERS-CoV since at least the 1980s [Some authors further specify that a reservoir should be defined in the context of another species of interest, called a target species . While tiliaris) ,35). Trailiaris) . Howeveriliaris)  in sever in 2009 . Althougintained .  found positive for SARS-CoV-2 during the COVID-19 pandemic that, up to now, seem to become infected by their owners, but do not play a larger epidemiological role [Further, the sporadic identification of microorganisms in a wildlife host is not direct evidence for its role as a reservoir . Indeed,cal role . Thus, lcal role , and speEbolavirus have not been isolated from bats , a gold standard to identify a host . While numerous bat species appear to be regularly exposed to ebolaviruses and certainly play a role in the viruses’ ecology and dynamics, the natural reservoirs are currently unknown [In some cases, bats have been presumed to be the reservoir of pathogens when evidence remains limited and the conditions for determining a reservoir (see above) have not been fully met. For example, bats, and in particular bats in the paleotropical plant-visiting family Pteropodidae, , are of unknown ,61. Recommended alternatives: “Reservoir” should only be used in cases that fulfill the criteria outlined above. When the ancestor of a pathogen is suspected to have originated in a particular taxon, this taxon should be referred to clearly as an ancestral reservoir, the reservoir of a common ancestor, or the reservoir of related microbes, which should be as specific as possible (possible . For exapossible . A reser(iii.) Intermediate host Definition: The term “intermediate host” was first used to describe multi-host parasites, such as helminths or protozoa that grow or complete a part of their life cycle in one or more hosts (the intermediate(s)) before infecting their final, definitive hosts, where their sexual phase occurs [e occurs ,63. Pteropus bats are reservoirs of Nipah virus  [Sus scrofa domesticus) [Pteropus medius [“Intermediate host” is frequently used in reference to viruses but there is no standard definition in this context. This term has generally been used to indicate species, often domestic animals or livestock, that facilitate the spillover of microbes from wildlife to humans. Hosts that have been described as “intermediate” are often domesticated or peridomestic  and therefore presumed to have higher contact rates with humans than the wild reservoir species or community, so that they act as a bridge between the two. In other cases, the virus can be amplified or might undergo selection for improved transmission in the intermediate host, further favoring spillover . Howeverampyrus) ,67,68,69esticus) ,71. Trans medius ,73.Appropriate use: “Intermediate host” is appropriately used when referring to hosts that are infected by a multi-host parasite in its immature form before infecting the definitive host [ive host ,63. We rCaveats: We caution against using the term “intermediate host” in the context of zoonotic viruses, in large part because there may be confusion and inconsistency between the categorization of host species as “intermediate hosts” or reservoir hosts. This is partially due to temporal ambiguity: a host described as “intermediate” for a virus can become a reservoir host if the virus is able to establish and maintain an infectious cycle in it through transmission to susceptible individuals. This new reservoir can become the primary source for human infection due to higher contact rates with humans compared to the original reservoir species. The microbe may also undergo selection in the “intermediate” host that favors either human transmissibility or pathogenicity. In this case the microbe may become sufficiently differentiated from its ancestor and adapted to the “intermediate host” that the “intermediate host” then becomes the reservoir of this new microbial species or strain that has diverged from the ancestral microbe found in the ancestral reservoir (see “Bat origin” for further discussion). Camelus dromedarius) in contributing to the emergence of MERS-CoV as a human disease is widely recognized [For example, the critical role of dromedary camels  and raccoon dogs (Nyctereutes procyonoides) are frequently described in both the scientific literature and popular media as “intermediate hosts” of SARS-CoV-1 although it is still unclear if these species were involved in spillover to humans [In some cases, there is simply not enough evidence to definitively determine whether a species played the role of an “intermediate host.” For example, palm civets  Vector (Type 2)Definition: The definition of “vector” varies considerably across disciplines. In the context of infectious disease transmission, the various definitions and contexts for the term “vector” have been recently reviewed by Wilson et al. [n et al. . One of n et al. ,83. Thisn et al. ) in whicn et al. ,86. Appropriate use: In our view, defining vectors as arthropods that feed or land on vertebrates, invertebrates, or plants and thus carry and transmit pathogens to these hosts, is the most accepted and useful definition when dealing with vector-borne diseases, since it covers relevant aspects of vector biology . Another advantage of this definition is the distinction of a vector from an intermediate host, since these arthropods are micropredators that improve their fitness at the cost of the host (even if insignificantly) [icantly) , while dCaveats and common misconceptions or misuse: The term “vector” has been loosely applied to cases in which organisms other than arthropods are capable of infecting a person or other animals to the infectious agent. Examples of this usage include rodents and hantaviruses [Canis lupus familiaris) and rabies virus [aviruses  and dogses virus . The WHOes virus . Using tes virus , to whicRecommended alternatives: We suggest avoiding “vector” when referring to non-arthropod hosts of pathogens and instead stating that the pathogen is “transmitted by” the species in question. Vertebrates may be referred to as a host or reservoir of the pathogen as appropriate (see Reservoir). Specifying “invertebrate vector” may also aid in avoiding misunderstandings.b. Processes and Events(i.) Spillover (Type 3)Definition: A spillover is an event in which a microbe is transmitted from one species  to a novel, susceptible species, establishing infection in this individual new host [new host ,93,94 , and references in films such as Contagion (2011) or Outbreak (1995). It is important to emphasize that spillover does not necessarily lead to a larger scale outbreak and could result in only a single case of infection in humans [eadlines , book tin humans . For exatbreak 19. It is in humans . When epn humans  or the 2n humans .Recommended alternatives: The term spillover should be only used referring to the initial cross-species transmission event of a microbe. It should not be used as a proxy for an outbreak or the existence of a wildlife zoonosis more generally. (ii.) Spillback (Type 1)Definition: Spillback generally indicates a specific case of spillover (see Spillover) when microbes spill from a new host back to the original host [nal host ,104  around Yellowstone National Park. Cattle had likely transmitted Brucella to wild ungulates, who then became a source of infection for cattle where they came in contact [Odocoileus virginianus) in North America [Meles meles) in the UK [Neovison vison, recently revised as Neogale vison [ contact ,106. Oth America  or from n the UK  and the le vison ) to humale vison . Caveats and common misconceptions or misuse: Recently spillback has been used to generally describe the spillover of zoonotic pathogens from humans to any animal species [Peromyscus maniculatus) [ species , such as species  or deer culatus) . Becauseculatus) . Recommended alternatives: Spillback should refer to spillover events from a new host back into the original host species. In all other cases of transmission of microbes from humans to wildlife, “spillover” or “cross-species transmission” is preferable. “Pathogen pollution” is another term that can be used to refer generally to anthropogenic introduction of pathogens to new areas and hosts [nd hosts .(iii.) Mutation (Type 3)Definition: A mutation is a change in a nucleotide sequence (DNA or RNA), such as substitution, deletion, or insertion. These changes may affect a single base-pair or many base-pairs. Mutations may be beneficial, neutral, or deleterious. Caveats and common misconceptions or misuse: The meaning and significance of a “mutation” can easily be misunderstood by the public. This may be due in part to the way the term is used in science fiction and popular culture, where it is often associated with a massive transformation or the acquisition of dangerous characteristics. However, mutations in the natural world are often neutral or deleterious to the organism or may not impact its phenotype [henotype ,116. In henotype . In addihenotype  have recAppropriate use: While the use of “mutation” in scientific literature is correct, we urge caution when communicating results regarding mutations to the media and the public, avoiding sensationalizing and limiting speculation. Extensive experimental and epidemiological data is needed to determine the effect of mutations on the transmissibility or virulence of a virus [ a virus . Until sc. Descriptors:(i.) Novel/New (Type 3)Definition: Novel or new is applied to anything that is being observed or described for the first time, such as a novel virus or a new animal species.Caveats and common misconceptions or misuse: In the context of a “new” species of plant or animal, it is generally understood by biologists that the species itself is not new, but it is being newly described by scientists .However, in the case of microbes or pathogens, using the terms “new” or “novel” could be misconstrued to mean that they did not exist before and have only recently evolved. In most cases, these “new” or “novel” microbes are simply newly described by science. There can be further confusion when organisms are truly novel, having only recently evolved, such as the emerging, novel variants of SARS-CoV-2 ,119,120.Recommended alternatives: We recommend using “newly described”, “newly identified”, or “newly discovered” as more accurate phrases when referring to microbes or pathogens that are observed or described for the first time. The term novel should only be used if there is evidence to suggest the microbe has (very) recently evolved.(ii.) Endemic (Type 2)Definition: Endemic has a distinctly different meaning in general ecology compared to epidemiology, and by extension disease ecology. In ecology and biogeography, endemic means a species is native to an area, usually with a restricted geographic distribution. For example, island endemic species are species that occur on a specified island or islands and nowhere else. This usage was coined by Charles Darwin in The Origin of Species [ Species .In contrast, in epidemiology, endemic refers either to a disease that is persistently prevalent in a given geographic area or a geographic area in which a disease is persistently prevalent with no sudden changes within a given time period ,123,124.For diseases circulating only in animals, the equivalent terms are enzootic and epizootic , althougAppropriate use: Clearly, the use of endemic in both the ecological and epidemiological sense is correct. In order to avoid any misinterpretation or ambiguity, we suggest that authors simply state clearly the definition or sense in which they are using “endemic.” Further clarity of epidemiological use can be conferred by specifying geographical extent and relative time scales.(iii.) Bat origin Definition: There is no standard definition of “bat origin.” This term has been used to describe both microbes isolated from or detected in bats [ in bats ,129 and  in bats ,112,130.Caveats and common misconceptions or misuse: In the case of SARS-CoV-2 “bat origin” has clearly been used as shorthand to illustrate the evolutionary relationship between ancestral bat coronaviruses or sister groups of bat coronaviruses and SARS-CoV-2. However, this use is easily misinterpreted by both scientists who are not experts in virology or phylogenetics, and the public, who may incorrectly understand such phrasing to mean a pathogen that is transmitted directly from bats to humans, that is, that they are the origin of the pandemic [Rhinolophus [pandemic . Rather,nolophus . This conolophus ,129. Recommended alternatives: For pathogens whose ancestor came from bats, but which have not themselves been detected in bats, we suggest instead using the phrase “virus descended from an ancestor found in bats,” “diverged from a bat virus”, or “evolutionary bat origin.” This type of phrasing emphasizes the evolution of viruses from an ancestor found in bats as well as the time for such divergence to occur, while also differentiating the current virus we observe from related species found in bats.(iv.) Bats (Type 1) Definition: The term “bats” is a common name that can refer to the entire order Chiroptera, several species within the order, or more than one individual of a single species. The order comprises over 1400 known species [ species , encompa species ,131. Bat species ,133,134, species ,136,137, species , and whe species . Life hi species . Differe species . Bat species also vary in the types and closeness of contact they have with humans. Some species are completely intolerant of any human disturbance and thus are restricted to unmodified habitats, while others are synanthropic, meaning they share human dwellings, even in dense urban areas ,144,145.Caveats and common misconceptions or misuse: “Bats” is widely used as a synonym for the entire order Chiroptera. Although some papers may report the taxonomic and ecological diversity of bats, they rarely recognize the significance of this diversity for species-specific trait combinations that influence both the disease dynamics themselves, as well as the size and riskiness of the human-bat interface. For example, an elusive, solitary rainforest species likely presents less potential risk than one roosting in large mixed-species aggregations in caves regularly visited by people [Wall Street Journal article from 9 April 2020 entitled “The bats behind the pandemic” followed by the subtitle: “From Ebola to Covid-19, many of the deadliest viruses to emerge in recent years have the same animal source” [y people . In part source” . While tThis “lumping” of species extends to inference from studies as well. Most field and laboratory studies can only focus on a small subset of bat species, but findings are often implicitly extended across taxa and contexts. Similarly, if “bats” is being used to denote multiple conspecifics, it may imply that all individuals within populations are currently infected by a virus, even when prevalence is low. López-Baucells et al.  found thRecommended alternatives: While all bats have wings, only some bats  currently host a particular virus, especially one that is pathogenic to humans or other animals, and even fewer bat species have been demonstrated as reservoirs (see definition above). Whenever possible, it is best to specify the family, genus, or species of bats being discussed and report the prevalence of microbes detected in each bat species in order to avoid implicitly extended findings to all bat species. Common names may also be included, particularly for communication with the public. Efforts should be made to incorporate the ecology of bat species and any specific contact pathways they might have with humans when discussing the results of disease ecology studies in bats [ in bats .d. Methodologies:(i.) Serology (Type 4)Definition: Serology is the detection of antibodies in the blood serum of an animal induced by an infection with a particular microorganism, which provides evidence for past exposure to that microorganism [organism .Appropriate use and interpretation: Serology overcomes several challenges related to the direct detection of microbes in wildlife, including bats, and is widely used to study the ecology of wildlife diseases. Compared to infectious agents, which are difficult to isolate or detect and soon cleared by the host immune response, antibodies last longer in the individual and can be found in the blood regardless of the organs targeted by the infection, the infectious status of the animal, or the occurrence of shedding at the moment of sampling [Rousettus aegyptiacus [sampling . Serologsampling . This cayptiacus . Seroconyptiacus ) In addition, antibodies elicited by a microbe can cross-react with other microbes in the same genus or family that show antigenic similarity . This inFlaviviridae [While this cross-reactivity makes it challenging to discriminate between the circulation of related microbes, such as viruses in the family iviridae , it repriviridae . For exaiviridae ,164,165.While serological findings alone do not constitute sufficient evidence to resolve the role of a species as reservoir hosts for the human pathogens targeted and used in the assays, these surveys provide strong evidence when coupled with genomic detection and are critical for describing and understanding the exposure history of bats to different groups of viruses ,163,166.Caveats and common misconceptions or misuse: While the detection of antibodies can provide useful information on the spread and dynamics of microorganisms in wildlife, it is crucial to acknowledge that serology only provides evidence for past exposure and cannot be used as a proxy for infection or disease [Bos taurus) actively infected with pathogenic Leptospira can still test seronegative [ disease . For exa disease ,168,169.negative ,171. In negative . FinallyAnother pitfall of the use of serological assays in wild animals is the likelihood for cross-reactivity between the target microbe and other related infectious agents, known and unknown. This means that a serological test can be positive even if the individual has never come in contact with the microbe of interest due to antigenic similarity . For exaFinally, the use of serology for the study of microbes in wildlife may be limited by: the unknown specificity and potentially poor accuracy of the test used; the validation and standardization of the tests in different host species, including true positive controls; and the uncertainty in defining the cut-off values used to differentiate between positive and negative individuals . In addiRecommended mitigation strategies: As shown, it may be challenging to make certain inferences from results of serological assays, as they are often made based on a number of assumptions that may or may not be fully justified [ustified . Among tustified . Additioustified . Attemptustified .(ii.) Phylogeny (Type 4)Definition: A phylogeny is a hypothesis that is tested to determine the evolutionary history and relatedness of organisms by comparing the similarity of different taxa. Although here we focus on phylogenies reconstructed using molecular data, as they are generally the most relevant for pathogens and disease ecology, we note that phylogenies may also be reconstructed using other types of data, such as morphology [rphology . In molerphology . An evolPhylogenetic trees based on molecular data are usually reconstructed using either a Maximum Likelihood (ML) method  or a BayCaveats and common misconceptions or misuse: A phylogeny is a working hypothesis because it draws only from the input data and therefore it is only as reliable and accurate as the information used in its reconstruction. Poorly curated alignments and selection of unrepresentative sequences can result in incorrect estimations of ancestral relationships. Incomplete datasets can misrepresent how close or distant a relation is between two adjacent branches. This can be a common issue when newly-described viruses emerge because there are relatively few reference sequences (sequences from related strains or taxa) available for comparison. A paucity of reference sequences, sampling bias, and selecting an inappropriate root sequence often produces phylogenetic trees with unsupported branches, resulting in inconclusive relationships [ionships . Furtherionships  and why ionships . The robionships . It is aionships . Furtherionships . Howeverionships .The choice of gene(s) used to build a tree is also important and will affect the results of any phylogenetic analysis. The choice of gene should reflect the question being asked . For virRecommended mitigation strategies: Researchers should carefully consider the gene(s) used to create a phylogenetic tree and use genes that are appropriate for the taxa of interest, based on breadth of taxonomic sampling, orthology, and rate of evolution. Orthologous genes are inherited from an ancestral gene and have diverged over time. They are identified either de novo using tree- or graph-based methods or inferred based on comparisons to known reference orthologues [hologues . As noteRdRp in the ORF1ab and may only be a few hundred base-pairs long [Multigene phylogenies should be generated whenever possible, although for some viruses this may not be possible due to the difficulty of designing primers and amplifying regions outside of certain highly conserved regions. Caution should be used when interpreting phylogenies based on short sequences or a limited number of genes. For example, many phylogenies for animal coronaviruses are based on sequences of irs long . Global irs long ,197. A rirs long . This stIn an ideal world, audiences would have greater domain knowledge and more time to review content carefully, report accurately, and thus avoid serious miscommunication. However, because audiences in this context include scientists from other domains, journalists, and the general public, this is not a feasible solution. The onus is therefore on domain experts as messengers to prevent miscommunication by avoiding ambiguity, being aware of points of confusion, sharpening their usage of terminology, and embedding clarification directly into content. At the same time, scientists from other disciplines should be careful about adopting and using words without being clear on their meanings and inference. This is a key component of interdisciplinary research. Preventing and minimizing miscommunication regarding bats and zoonotic diseases is important because failure to do so has serious negative consequences for understanding disease dynamics, developing effective mitigation or prevention strategies, and conservation efforts. For example, correctly identifying reservoirs, bridging or amplifying hosts, or origins of pathogens is essential for effectively researching and thus further understanding their ecology, host specificity, transmission dynamics, and pathways of spillover. Similarly, broadly describing “bats” as hosts of pathogens or emerging diseases rather than specifying species, genera, or families implicitly conceptualizes 1400+ different species as essentially the same biological entity, limiting our understanding of the ecology of specific microbes in their specific host species. Since any risks posed by microbes within hosts are species-specific, accurate specification is critical to support inference in disease ecology research. While some studies deliberately choose to use only a few representatives of each taxonomic group to compare patterns among higher taxonomic groups , we urge caution in interpreting such results for the reasons outlined above.Pteropus, such as moving pig sties away from orchards or using skirts to cover date palm sap receptacles has helped prevent the spillover of Nipah virus to pigs and humans [Clear communication, including correctly identifying and describing the reservoir, bridging hosts, or origin of a pathogen, is also essential for designing and implementing effective strategies for preventing and mitigating zoonotic disease spillover because these measures largely rely on managing the distribution of reservoirs or other hosts, reducing the prevalence of the pathogen in these species, or minimizing interactions between hosts and target populations . The mosd humans ,72,201. d humans ,46,184, Rhinolophus alluded to by the term “bat origin” has led people to incorrectly believe that SARS-CoV-2 is directly transmitted from bats to people [Rhinolophus do not occur in North America and local Arkansas bat species have no link to COVID-19 or SARS-CoV-2 [Finally, miscommunication regarding zoonotic diseases can have harmful effects on conservation. In general, incorrect usage of “reservoir”, “vector” or implying that all individuals of all bat species are dangerous and carry viruses pathogenic to people can provoke fear and negative attitudes towards bats, especially when interpreted or sensationalized in popular media ,9. Most o people . FurtherRS-CoV-2 . IncorreRS-CoV-2  can exacRS-CoV-2 .Some of the terms we have identified lead to miscommunication with potentially lower stakes but nevertheless have implications for research or public understanding of disease ecology. For example, “endemic” has a radically different definition in ecology compared to epidemiology and misunderstandings can hinder interdisciplinary research and collaboration or the interpretation of results by experts from different domains. In another case, incorrect inference of the term “novel” can affect public perception of pathogens and diseases. Believing that a “novel” pathogen is newly evolved, rather than newly described by scientists, may raise a much greater alarm in the public and instill a false sense that many more species of pathogens exist and that they evolve more quickly than they actually do. This may be compounded by using “novel” in this more literal sense, for example, in reference to newly evolved strains of SARS-CoV-2 ,119,120.We note that we are not creating new definitions or terms and most definitions that we point to are well-established in disciplines, although in some cases, such as “reservoir” ,32,200, Our list of terms subject to miscommunication is clearly not exhaustive. We selected those that we believe are causing the most confusion and misunderstanding in the current COVID-19 crisis, and that have downstream consequences for public health policy and practice, and biodiversity conservation. Although we focus on bats, miscommunication surrounds these terms in research and discussions of other taxa involved in emerging infectious diseases . Nonetheless, there are many more terms and contexts causing confusion, and this is only likely to increase with growing appreciation and application of One Health approaches, which by their very nature are at minimum multidisciplinary and at best interdisciplinary. While the amount of interdisciplinary One Health research has grown, there is still a certain level of separation between subdisciplines due to differences in study systems, questions, and methods ; a shareIn this vein, we propose solutions for each type of miscommunication . For TypThe problems identified above are not exclusive to the written word. The public and policy-makers are generally not reading academic journals, but getting information from sound bites, videos, and interviews disseminated via traditional news outlets and social media ,208,209,


Narrative medicine (NM) is an approach involving narrative skills and is regarded as a model for medical humanism and effective medical practice. This study aims to explore how NM impacts medical trainees’ learning of professionalism during a clerkship in a Taiwanese clinical setting.A qualitative interview study adopting a purposive sampling method was undertaken. Thirty medical trainees participated in this study, including five fifth-year medical students (MSs), ten sixth-year MSs, nine seventh-year MSs, and six postgraduate year (PGY) trainees. Thematic framework analysis was applied, and a modified realist evaluation approach was further used to analyse the interview data.We identified self-exploration, reflection, and awareness of professional identity as mechanisms explaining how NM impacted professionalism learning in our participants. Furthermore, empathy, communication, doctor-patient relationship and understanding patients were identified as the outcomes of the NM intervention for trainees’ learning of professionalism.NM facilitates medical trainees’ self-exploration, reflection, and awareness of professional identity, thereby affecting their learning of professionalism in clinical settings. Adopting NM as an educational intervention in undergraduate medical education could play an important role in professionalism learning, as trainees can thereby be supported to gradually develop self-exploration and reflection capabilities and heightened awareness of professional identity reflectively through a narrative process.The online version contains supplementary material available at 10.1186/s12909-021-02823-4. Narrative theory is based on the principle that people are inherently storytellers, storytelling being one of the oldest and most common forms of communication. People enter their social world narratively, making decisions and taking action within this narrative framework . Rita Chhttp://www.acgme.org). Professionalism has been defined as a group of attitudes, values, behaviours and interactions that serve as the basis of the health professional’s contract with society  just turn the clinical situation into a story, in which you stay away from your perspective and you observe the parts that are reasonable and worthy of discussion (C6D). I think the purpose of this (NM) curriculum is to change our thinking (to understand) that we are not superior. We need to understand patients’ thinking from a different perspective, and we need to have more practice. Yeah. In this way, we can help the patients communicate… (C6B).[When you] face a difficult situation or difficult person, sometimes your responses and emotions might be affected. At that time, I thought humanistic medicine is like a small garden in your heart, and this unpleasant situation or another, the bad attitude or a difficult family are like the storms trying to smash your garden. And humanistic medicine is like, like the sun, or something else. It reminds you that you still have to … you still have to keep some basics in the medical field, which is your original intention. You are responsible to these people. (…) sometimes they would jump out and shed light on the garden, reminding you to not let the garden be destroyed because of the temporary storm (7D).But values cannot be changed overnight. Values are changed in people’s sub-consciousness. This activity  basically comes with medical humanities. I don’t think it’s possible to change your patients, so I think what we can change is from the side of medical staff or so that medical staff shows their kindness. If (you) want to build a good relationship, there must be one side showing its kindness first. I think what narrative medicine is about is to change the doctor’s values (6B).Speaking of empathy, I think this is a matter of medicine… the training which is given in medical humanities is more like, um, probably the person is empathetic in nature. When he is taking the curriculum, he would feel he can relate to it (to empathy) (5A).Well, because in the process of performing narrative medicine, we have to chat with patients and family members in a very effective way. We must know the patient very well. If we want to understand him, we must use a lot of empathy. It's like a skill or a way that it can break through people's heart. So that it makes strangers want to talk to you, that kind of feeling. (8B)Medicine is about communication among people. It’s not like a repair shop on the street, although what we are doing is more or less like fixing stuff. But what we fix are human bodies. So we have to consider their feelings. We cannot do whatever we like. We have to obtain his (the patient’s) consent because sometimes he would also feel not well, and we also have to take care of his feelings (8F).I mean when you have the other [patient], you would feel familiar with the patient’s illness. I think it’s practical. And another thing is that you can think about the interaction process you have with the patient, which is the way you build a relationship (C7B).‘Cos now there are many medical disputes, and many of them are due to bad doctor-patient relationships. And this (NM course) enables us to help patients and restore relationships with them. In this way, medical disputes might be reduced (C6B).Actually, I think narrative medicine has an advantage, which is you can understand the patient’s medical history and diseases better, because usually we will do the medical interviews in narrative medicine (C7B). [So] I can better understand why he made the choice at that time, because I had a patient who lost his job due to his illness. At that time [I] asked him why he was not working or something else. And you learn that actually this illness had become a burden in his life, and after that, when you are delivering health education to the patients, you can be more understanding of their situation. (You can) be understanding of their worries or pains (C7A).So suppose you were just on duty, and you just met the parents during that time, you would think they were crazy. It was just pneumonia, unnecessary to be that neurotic. But when you tried, tried to understand more details, you would gradually realize the underlying family issues (8A).We identified eight themes and categorized them as the mechanisms of the impact of narrative medicine and the outcomes of narrative medicine in terms of the professionalism of medical trainees. We categorized “self-exploration”, “reflection”, and “awareness of professional identity” as the mechanisms and categorized “empathy”, “communication”, “doctor-patient relationship”, and “understanding patients” as the outcomes of the narrative medicine intervention. The NM intervention enhanced medical trainees’ observation of and interaction with their patients and facilitated a process of self-exploration, reflection, and awareness of professional identity, thereby affecting learning outcomes for professionalism within the clinical environment. Promoting NM learning within undergraduate medical education can influence trainees’ professionalism learning outcomes through a reflective narrative process.Self-exploration is an increasingly aware, imaginative, and enduring practice. It can be used to identify and challenge one’s assumptions and behaviours based on new information generated by exposure to new environments and the passage of time , 23. By In medical education, reflection has been integrated into various training programs  and is rThe significance of our research includes a discussion of the professional identity of budding doctors and the factors that affect their professional development. The identity of a doctor is a self-representation achieved in stages over time. During these stages, the characteristics, values and norms of the medical profession are internalized, resulting in a person who thinks, acts and feels like a doctor . Accordiability to feel empathy is innate, possession of it does not necessarily mean skill in using it. Thus, medical educators have tried to develop exercises and techniques to foster empathy among clinicians [Empathy, one of the core components of professionalism, has been identified as an essential component of the doctor–patient relationship , 42. It inicians , 50. Preinicians . In the body as A machine metaphor (“medicine is not a repair shop” and “what we fix are human bodies”) to express the concept that patients are more than machines and that both doctors and students should handle them with care. Narrative medicine offers opportunities for respectful, empathic, and nourishing medical care by bridging the separation among physicians, patients, colleagues, and society [Good communication skills are an essential component of medical education. Doctors’ interpersonal and communication skills have a significant impact on patient care and correlate with improved healthcare outcomes , 53. In It is widely accepted that the ability to understand the patient is essential to the establishment of good rapport and effective doctor/patient communication . ThroughWe acknowledge several limitations in our study. The research was conducted in a single medical institution in Taiwan, although the research site is the largest training institution in the country. In this study, we focused on qualitatively evaluating the global impact of NM in a clinical clerkship on medical trainees’ learning outcomes with respect to professionalism rather than addressing the impact of the different levels of clinical experience of these participants. For some of the participants , the NM had taken place over 1 year before they were recruited for this study. Thus, the prolonged effect of the NM could vary among participants. A teacher-learner power relationship exists between the researchers and the study participants, and the extent to which this affects the data should be considered in future studies. Moreover, all medical trainees were compulsorily asked to complete one NM writing in this course rather than a voluntary NM writing, which could lead to bias.Narrative medicine facilitates medical trainees’ experiences of self-exploration, reflection, and awareness of professional identity, thereby affecting their outcomes in terms of learning professionalism in the clinical setting. Adopting narrative medicine as an educational intervention in undergraduate medical education could have impacts on professionalism outcomes, as trainees can thereby be supported in gradually embodying their self-exploration, reflection, and awareness of professional identity reflectively through a narrative process.Additional file 1. Semi-structured interview questions for medical trainees.


Loneliness is a public health concern, and increasingly, individuals experiencing loneliness are seeking support on online forums, some of which focus on discussions around loneliness (loneliness forums). Some of these individuals may also seek support around loneliness on online forums not related to loneliness or well-being (nonloneliness forums). Hence, to design and implement appropriate and efficient online loneliness interventions, it is important to understand how individuals who express and seek support around loneliness on online loneliness forums communicate in nonloneliness forums; this could provide further insights into the support needs and concerns of these users.This study aims to explore how users who express the feeling of loneliness and seek support around loneliness on an online loneliness forum communicate in an online nonloneliness forum.valence, arousal, and dominance, the language use differences in posts published in the nonloneliness forum by these users compared to a control group of users who did not belong to any loneliness forum on Reddit were determined.A total of 2401 users who expressed loneliness in posts published on a loneliness forum on Reddit and had published posts in a nonloneliness forum were identified. Using latent Dirichlet allocation ; Linguistic Inquiry and Word Count (a psycholinguistic dictionary); and the word score–based language features d=0.10) and seeking to socialize (Cohen d=0.114), and use words associated with valence (Cohen d=0.364) and dominance (Cohen d=0.117). In addition, they tend to publish posts related to latent Dirichlet allocation topics such as relationships (Cohen d=0.105) and family and friends and mental health (Cohen d=0.10).It was found that in posts published in the nonloneliness forum, users who expressed loneliness tend to use more words associated with the Linguistic Inquiry and Word Count categories on sadness (Cohen There are clear distinctions in language use in nonloneliness forum posts by users who express loneliness compared to a control group of users. These findings can help with the design and implementation of online interventions around loneliness. Loneliness is a public health challenge ; it affeSeveral prior works ,9,10 havUsing natural language processing methods, prior works determined that the language used in posts published on social media platforms and online forums can be used to gain insights into how users communicate on these forums and the types of support they seek and express, as it relates to their health and well-being. For example, language used in posts published on Facebook was used to train a machine learning model to predict patients risk for cardiovascular disease . In addiSimilar to prior works, in this study, using natural language processing methods, language used on posts published on a nonloneliness online forum are analyzed to gain insights into the support needs and concerns of individuals who express loneliness in a loneliness online forum. Potentially, information gleaned from the analyses in this study will provide further insights into the support needs and concerns of individuals expressing loneliness on online loneliness forums, thereby informing loneliness interventions./r/Lonely had more posts and members compared to the other forums, which each had less than 200 published posts during the time period in which the data was collected. Hence, for the analysis in this study, usernames of members of /r/Lonely were used; specifically, the usernames of 9956 users who had published a total of 15,012 posts on the /r/Lonely forum were selected.For the analysis in this study, data from Reddit was used. Reddit is made up of more than 1 million subforums   focused /r/Lonely, all the forums on Reddit were searched to determine the forums in which these /r/Lonely users tend to publish posts. It was observed that the forums with the most number of these users as members are /r/AskReddit (a forum in which users seek advice and ask open-ended questions on various topics) and /r/depression (a forum focused on discussions around depression) with posts by 24% (n=2401) and 20% (n=2031), respectively, of the /r/Lonely users (N=9956) in the data set. Since the focus of this study is to determine how individuals who express loneliness on an online loneliness forum communicate in nonloneliness forums , for all the analysis in this study, data from /r/AskReddit by 2401 users who expressed loneliness in /r/Lonely were used. The author reviewed the posts (N=4001) published on /r/Lonely by these users and observed that these users expressed feeling lonely in their /r/Lonely posts by stating that they were feeling lonely , implied that they were feeling lonely , or sought support as it relates to loneliness .To identify the other Reddit forums in which these users belong to and tend to publish posts, using the usernames from /r/Lonely and had published posts on /r/AskReddit were matched with a control group user who had no published posts on any loneliness forum on Reddit and had published posts on /r/AskReddit between December 2015 and August 2019.Each of the 2401 users who posted on /r/AskReddit posts by users who express loneliness compared to the control group: a topic modeling approach, a dictionary-based approach, and a word score–based approach. Cohen d, which indicates the standardized difference between means, was used to report the effect sizes. In this study, only results with Cohen d greater than or equal to a threshold  and that are significant at Bonferroni-corrected P values <.001 are reported.In this study, the following methods were used to determine language use differences in The topic modeling approach and the dictionary-based approaches were used because prior works used these approaches to gain insights from social media data about the language use differences between individuals in different genders  and age /r/AskReddit posts associated with /r/Lonely users and the control group users; to determine the number of LDA topics, the number of topics varied between 5 and 50 topics by starting with 5 topics and incrementing by 2 topics up to 50 topics. A total of 20 topics had the most coherent topic themes when reviewed by the author. With the generated topics, using the Dlatk package [/r/AskReddit posts by /r/Lonely users when compared with the control group users were identified.In this section, the natural language processing topic modeling method latent Dirichlet allocation (LDA)  was used package , the top/r/AskReddit posts associated with the /r/Lonely users and the control group users were used to determine the prevalence of Linguistic Inquiry and Word Count (LIWC) [/r/AskReddit posts , the proportion of token words associated with LIWC categories were determined.In this approach, language from t (LIWC)  dictionat (LIWC) ,22,27. Ut (LIWC) , for eacalence, arousal, and dominance have been used by prior works to study communication strategies in an online forum [Valence indicates the measure of the positive or negative denotation of a word; for example, “enjoyable” is a high valence word and “nightmare” is a low valence word. Arousal measures the emotional intensity expressed in a word; an example of a high arousal word is “exhilarated,” and an example of a low arousal word is “siesta.” Dominance indicates the measure of the locus of control expressed in a word; for example “powerful” is a high dominance word, and “weak” is a low dominance word. Mohammad [valence, arousal, and dominance for 20,000 words in English; using this lexicon, for each post in the data set, the average ratings of all content words in each of these word categories  was computed.The word score–based features vne forum ,28. Vale/r/Askreddit posts by /r/Lonely users compared to the control group./r/AskReddit posts most associated with /r/Lonely users compared to the control group users.d, the effect size between the features that represent the average valence, arousal, and dominance scores for posts in the data set and a feature that represents if a /r/AskReddit post was by a /r/Lonely user or a control group user was determined, as shown in Using Cohen Using natural language processing methods, this study shows the distinction in language use in posts published on a nonloneliness forum by users who express and seek support around loneliness in an online loneliness forum compared to a control group of users. These language use differences reflect the support needs and concerns of these users. The findings from this study are summarized in this section./r/Lonely tend to seek advice and ask questions about relationships on /r/AskReddit (This study determined that users who express the feeling of loneliness in skReddit  compared/r/AskReddit posts (rephrased) by /r/Lonely users seeking advice as it relates to their relationships with family members and friends:In addition, this study has findings that were not in prior work; specifically, it was observed that individuals who express loneliness in a loneliness forum tend to seek advice and ask questions about mental health concerns as it relates to their family members and friends; for example, the following are examples of I need advice on how to deal with a family member / friend who keeps criticizing me.I need help, if one is struggling with mental health, what is the best way to explain it to family members and friends?Using LIWC, it was observed that users who expressed loneliness in the loneliness forum tended to use more words associated with sadness and wanting to socialize in the nonloneliness forum.alence, arousal, and dominance, it was determined that the average valence and dominance scores in /r/AskReddit posts are more associated with posts by users who express loneliness on /r/Lonely. A potential explanation for dominance being more associated with /r/AskReddit posts by /r/Lonely users is that some of these users seek support and express vulnerability in these posts; low dominance words suggest vulnerability, hence the association. Additionally, a potential explanation for valence being more associated with /r/AskReddit posts by /r/Lonely users is that these users tend to use low valence words in these posts, hence the association.Using the word score–based language features vThis study shows that users who express loneliness in a loneliness forum seek support and communicate differently from a control group of users in a nonloneliness forum. The findings from this study can aid in the design and implementation of online loneliness interventions; for example, given that users who express loneliness in the loneliness forum ask questions and seek advice as it relates to their relationships (with family and friends) and use more words associated with seeking to socialize and sadness , online From this study’s findings, when designing and implementing online loneliness interventions, it is important to not only focus on user communication in loneliness forums but also look into how these users communicate in nonloneliness forums.In this study, data from Reddit users was used and may not be representative of all individuals (some of whom may not publish posts on online forums expressing their feeling of loneliness) who feel lonely./r/Lonely) was contacted. In addition, besides the usernames of /r/Lonely users, no other information from user profiles was used or accessed.The data set used for this study is publicly available. For all the analyses in this study, no user or moderator of any loneliness forum on Reddit (including , it was determined that users who express loneliness in an online loneliness forum communicated differently in a nonloneliness forum when compared to a control group of users. The findings from this study can aid with the design and implementation of online loneliness interventions.In this study, using natural language processing methods