Love Carefully: Use a condom, drawing on methodologies from both the history of emotion and literary analysis. The informative leaflet, produced collaboratively by the sexual health charities Brook and the Family Planning Association, was intended to prevent the spread of HIV among heterosexual adolescents, a group increasingly viewed as ‘at risk’ by adult producers of health education globally. Steeped in British teenage popular culture, it deployed an introduction from well-known teenage agony aunt Melanie McFadyean, a cartoon strip, and statements from celebrities. The cartoon offered a representation of the difficulties experienced by heterosexual teenagers negotiating the prospect of penetrative sex with a new partner, offering a successful example of condom negotiation, while sympathetically examining why some found condom use and AIDS difficult subjects to broach. The article argues the leaflet deployed emotions and authenticity to persuade teenagers to practise safer sex.This article examines the 1987 British AIDS education leaflet  Love Carefully—Use a condom to encourage condom use among heterosexual teenagers. Deploying an introduction from well-known teenage magazines, agony aunt Melanie McFadyean, a cartoon strip, and statements from popular teen celebrities, the leaflet was intended to prevent the spread of HIV amongst heterosexual adolescents, a group increasingly viewed as ‘at risk’ by adult producers of health education nationally and internationally. McFadyean’s informative yet chatty prose introduced the idea that British adolescents were at risk from the ‘AIDS virus’, which could be carried in ‘blood, semen (spunk) and infected vaginal fluids’ but protected against by using a ‘condom ’.In 1987, Brook,The emergence of HIV in the early 1980s presented a new challenge for public health policymakers and front-line health service providers, particularly for those working in sexual health and education. While this moment of urgent policymaking has been the subject of intense scholarly scrutiny, much of this history has been written as an assessment or corrective against the charges of moral panic levelled at the New Right governments of the 1980s and 1990s. It has been argued that the New Right used AIDS as an opportunity to roll back social reforms and attack identity politics in favour of moral conservatism in response to media moral panics.Love Carefully was celebrated by its producers for being the first education intervention of its kind.Love Carefully deployed a combination of techniques to advocate condom use. The leaflet drew on celebrity endorsements, tropes from teenage magazine culture and Brook’s knowledge of adolescent sex and gender politics ‘to specifically address the problems young heterosexual people’ experienced when trying to follow advice ‘on how to protect each other from AIDS’.Launched at an orchestrated press conference on 15 April 1987 at Brook’s central London office, Love Carefully from its inception, production, reprint and reinvention, tracing what was new and old about the leaflet’s representation of AIDS and adolescence. It discusses how it, and its use, changed as the field of AIDS prevention in Britain rapidly evolved and the educational needs of teenagers were reassessed. In doing so, the article deploys the leaflet as a lens through which to explore broader histories of British AIDS representation to adolescents for the purpose of health education in the last decades of the twentieth century. This article adds to an existing body of HIV scholarship that draws on the cultural products associated with the virus to explore its social, cultural and emotional history. The article helps to redress two significant gaps in the literature: the absence of a history of HIV which engages with this disease’s cultural impact upon childhood and adolescence; and the limited scholarship on those non-governmental responses to HIV which specifically addressed sexually active heterosexuals. Though this case study furnishes us with a specifically British, rather than global, history of the virus’ cultural impacts, the methodologies deployed and attention to teen culture argued for here can be applied to cultural histories of AIDS in broader contexts. By drawing out the peculiarities of British youth culture imagined and addressed in Love Carefully, this article sketches how Brook constructed heterosexual youth in the era of AIDS. It demonstrates the fundamental importance of a history, which takes the specifics of age seriously, while adding to the literature on NGOs and communities that played pivotal roles in the early fight against AIDS.This article explores Love Carefully and the first edition of the text itself. Here techniques drawn from Bakhtin’s theories on intertextuality and dialogics are deployed to analyse the ideological and ‘work-like’ constituents of the text—those textual constructions that supplement ‘empirical reality by adding to, and subtracting from’ it.Love Carefully a uniquely innovative and persuasive text, representative of Brook’s place in the wider sexual health education arena, and the institution’s feelings towards teenagers, their sexual health and their identities.The article begins by outlining Brook’s place in the sexual health education of adolescents before the AIDS crisis. This sketches the parameters of the sex education arena, outlining which institutions and policies were influential in the early 1980s. The article then explores how AIDS education provisions were affected by the recognition that teenagers, as an emerging ‘at risk’ group, had specific sexual health education needs requiring dedicated materials and interventions. This locates Brook in its historical, cultural and political contexts, outlining Brook’s initial response to AIDS in relation to other emerging AIDS-related health education provisions for adolescents, its relationship with government and its ties to the Family Planning Association (FPA). The article then offers a close reading of both the production context of Love Carefully, nor will it be possible to discuss Brook’s later forays into AIDS education, except in those cases where Love Carefully was drawn on and redeployed. Similarly, while the article is careful to place this text in the context of the adolescent AIDS education policy and media that influenced its creation, and to which it was a constituent, it is not the intention of this article to revisit the policy or the material cultural history of AIDS, which has already been written.Brook was (and is) a prolific publisher of sex education materials for use with, and by, adolescents. Unfortunately, it is beyond the scope of this article to discuss the precursors to Awareness of AIDS in Britain emerged towards the end of 1981, with the first responses to the disease largely provided by voluntary communities of homosexual men who came together over the course of the 1980s to raise money for research, to provide support to loved ones, and to disseminate information about AIDS.The mid-1980s was also marked by AIDS’ transformation into a public health priority as its spread among heterosexuals was established and the virus isolated and identified. It is often suggested, in both lay and scholarly histories of HIV, that the advent of the AIDS crisis initiated increased openness around sex, especially in discussions with adolescents.Just Seventeen from its launch in 1983. Magazine feature writers and agony aunts took an active interest in the services provided by both the FPA and Brook, advertising their services and contact details whenever relevant.MIZZ magazine and Melanie McFadyean of Just Seventeen played pivotal roles. Agony aunts lent their expertise in sexual health promotion and teenage magazine production to organisations like Brook and the Health Education Authority (HEA), in addition to producing sexual education materials for the magazines themselves. Consequently, the HEA, recognising magazines’ unique ability to reach adolescents, placed health education adverts for five distinct AIDS education campaigns in several leading teenage magazines between 1988 and 1996.Sex sold magazines and thus created opportunities for alliances between Brook, the FPA and sympathetic members of the magazine industry. Indeed, discussions of contraception and visits to Family Planning or Brook clinics formed regular features in Beyond the pages of teenage magazines, childhood, education and teenage sexuality were repeatedly discussed within the public sphere. Sex education policy, and more broadly policy related to the rights and needs of the child,In part the proliferation of legislation around children’s rights and education was a result of, as Durham observes, the New Right’s willingness to opportunistically respond to ‘populist’ demands, which aligned with their intention to restructure the education system and critique the Left.Gillick brought legal proceedings against the DHSS and her Local Health Authority (LHA) in 1982 for refusing to promise to withhold confidential contraceptive advice or treatment to her underage daughters.Love Carefully.The courts ruled against Gillick in 1983, judging that medical professionals were neither in breach of the 1956 Act, nor did parental authority constitute ‘rights’ as they had no protection in law; rather parental authority engendered a responsibility.Outside the clinic and within school walls, legislation bolstered parents’ power, rather than children’s agency. For example, during the 1980s, school governance was restructured through both legislation and non-statutory circulars to ensure more parents were included on governing boards and to reinforce parental powers within the school system generally. Key among such legislation was the 1986 Education (No.2) Act, which transferred the authority to develop a sex education curriculum from LEAs to school governors.Though it is important to consider how and what the government legislated around sex education and children’s rights, a wide variety of actors were able to influence children’s sex education in this period without legislative power. The government’s direct power was diluted by a structure, which had governed sex education in Britain since the 1960s, characterised by a ‘series of sub-contracting operations’, wherein NGOs were paid by government to deliver sex education.In Britain, in the latter half of the twentieth century, formalised sex education remained firmly cast, as it was from its Victorian inception, as ‘a strategy of damage limitation’, the focus fixed on preventing unwanted pregnancies, moral decline, disease or loss of social status, rather than the possibilities of ‘pleasure and empowered choice’.I use the terms optimism and pessimism here to draw attention to the emotional difference that lay behind these disparate visions of the child and childhood: visions of the child as an agentic figure are imbued with hope for the future; those imagining a vulnerable innocent steeped in nostalgia, viewing the future as fearful. These constructions of the child were both generative and indicative of the ideals of adults existing within particular emotional communities. Emotional ties to some degree account for productive relationships between institutions, despite varied levels of judicial and legislative responsibility and power, and in some cases, near-constant clashes over territory and jurisdiction. Here I draw on Barbara Rosenwein’s concept of the ‘emotional community’ to guide my analysis. Analogous to ‘social communities’, their emotional nature is discovered through the attention of the researcher to the ‘systems of feeling’ that govern them. These systems amount to shared definitions of what individual members and the collective community ‘define and assess as valuable or harmful to them’; assumptions about the emotions of others outside the community; ‘the nature of the affective bonds between people that they recognize; and the modes of emotional expression that they expect, encourage, tolerate, and deplore’.Love Carefully begins first with the imagining of an audience by the text’s creator(s); the situated but imagined receiver(s) reacting to context and text according to the hopes and fears of the author(s). Reading authorial intent, ideology and emotion off a text like Love Carefully by excavating the audience imagined by it in this manner is a fruitful undertaking, rendering the sub-textual normative narratives of childhood and sexuality underlying such texts available to scrutiny. Love Carefully was a text representative of a particular emotional community; the creation of it a political act born of the desires of one emotional community—Brook and FPA—to intervene in their vision of an emotional community of teenagers. An attempt to intercede in the lives of an imagined audience presumed to be in possession of particular emotional dispositions and governed by certain emotional regimes and consequent behaviours—in this case, the use or rejection of condoms.To excavate these ‘systems of feelings’, I draw on Lacanian literary critique, which maintains that the creation of a text such as Love Carefully among teenagers is not the subject of this article, an awareness of the dialogic and intertextual nature of texts, and so their relation to the ‘ongoing social and political transformations’ that produce and give them meaning, is vital.Approaches that borrow from Lacan, as this one does, can suffer from a degree of myopia, placing authorial intent and emotion in view while losing sight of the audience as a living, varied, fluctuating, agentic and fractured object. The audience is an entity whose context, emotions and experiences render them as much the creator of the text’s meaning as the original producers. An attention to intertextuality—the referential nature of texts, their dialogic quality and their ‘work-like’ aspects—foregrounds the primacy of prior audience knowledge, emotion and context in shaping the reception and meaning of a text.Love Carefully alongside Brook AIDS Concern, to enjoy more freedom. Consequently, OSPG largely avoided embroilment in the territorial clashes, which marked DES dealings with other NGOs operating in schools, and it was less restricted by the evolving obstructive education policies of the 1980s and 1990s.The first Brook centre was opened in London in 1964 by its founder Helen Brook. Two years later, the Birmingham Brook centre was opened, acting as a base in the Midlands but also providing the location where the Education and Publications Unit would later operate.Love Carefully, a leaflet initially paid for and produced at the behest of the DHSS.However, while the OSPG was influenced by, rather than subject to, the rules governing school-based sex education, the group was limited by the requirement to differentiate its work from the FPA’s Publication Unit, lest Brook and the FPA lose Department of Health (DoH) funding due to perceived duplication of services.The need for a specific response to AIDS intended for the consumption of heterosexual adolescents was recognised by front-line Brook workers who were increasingly ‘finding that young people […] picked up a lot of information about AIDS, but […] developed over-bearing fears and worries about the disease’.By 1987 limited consensus about the AIDS education needs of teenagers had evolved, with themes such as myth busting, dismissing bigotry, consent, and condom negotiation appearing across a variety of teenage media, including texts produced by the government. This was in part the result of the collaborative forum in which AIDS policy was written, with organisations like the HEA, BMA and FPA sharing key members and borrowing policy and practice from one another as they attempted to navigate the ideological minefield of sex education and children’s rights without aggravating the DES.The idea of AIDS ‘myths’ reoccurs across both the internal archives of institutions involved in the public health campaigns against AIDS and as an explicitly addressed problem in the materials produced for adults and adolescents.Love Carefully was produced, disseminated, reprinted and repurposed.Ambiguity gave those providing education to adolescents a degree of wriggle-room, allowing them to follow their own agendas. Those who pessimistically felt that sex education was a corrupting influence were left able to provide the bare minimum within curriculum parameters. Meanwhile, more optimistic educators argued for, and produced, more explicit information, believing it held greater protective or empowering potential. This resulted in wide variations in the AIDS education of adolescents in Britain across the late twentieth century, both within and outside the formal education system.Love Carefully explained, ‘By suggesting ways of raising the AIDS issue and discussing condom use with their partners’, the leaflet aimed ‘to help young people, particularly young women, develop the assertion skills they need to protect themselves from AIDS.’As the 1987 press release for Love Carefully from the DHSS and Chief Medical Officer and ‘a grant from the DHSS’ to fund printing.Love Carefully from interested members of both charities and later met with the FPA’s head of publications, Helen Martins, and her team to consult directly.Love Carefully was launched on 9 April 1987, less than 3 months after the FPA was first asked for input—was facilitated by ties between the publication arms of Brook and the FPA made necessary by earlier DHSS stipulations regarding duplication of services.Love Carefully throughout the 1980s and 1990s. Agreements over what should be done about AIDS quickly led to more fraught considerations of how shared aims should be delivered on, by whom, where and when. Indeed, as will now be discussed, precursors to later disagreements and concerns are detectable in the ultimately fruitful collaborative production of the leaflet.Pressed by the DHSS to produce an AIDS education leaflet targeting heterosexual adolescents quickly, Brook ‘by-passed the normal committee consultation’ in deference to ‘the urgency of the situation’, receiving speedy approval for Love Carefully in late January 1987. The first round of comments from the FPA’s AWG included contributions from FPA medical officers and Alastair Service, the FPA General Secretary, former Vice-Chair of the dissolved Health Education Council and the then Vice Chairman of the HEA.The FPA’s AIDS Working Group (AWG) were sent photocopies of Melanie McFadyean’s introduction, cartoon strip script and the proposed layout for catch AIDS. You get HIV which might or might not lead to AIDS eventually. It is simpler to talk about AIDS, but creates misinformation’ .Love Carefully that simpler messages would carry greater persuasive force. However, so too were worries about what meaning might be lost, or worse misapprehended, in seeking this simplicity. Indeed, Belfield later repeated ‘you can’t catch AIDS’ in reference to Love Carefully’s cartoon script, again with emphasis.Concerns expressed by Service regarding what information was present and absent in the first draft of McFadyean’s introduction acknowledge the powerful effect of constructed ignorance. Service complained it ‘says very little about how disease works & what it is’ and wondered charitably ‘is this deliberate to keep it short?’ In a similar but more critical vein, Toni Belfield, a medical information officer for the FPA, argued for greater ‘educational input’, feeling it was vital to make clear ‘you can’t Love Carefully’s producers were concerned the text might make teenagers more fearful by normalising anxieties through depicting them in the cartoon. The cartoon script, which changed little between its first draft and publication, opens with Sylvia discussing both her desire to have sex with Jim and her fear of AIDS with her friend Jane. Jane responds by suggesting they use condoms. Following Jane’s advice, in the next scene, Sylvia broaches condom use and her AIDS fears with Jim. He reacts badly, exclaiming ‘Are you suggesting I’ve got AIDS?’. Sylvia hastily responds ‘No! It’s just that everyone is at risk now, even you and me. We have to use condoms; they help stop the AIDS virus being passed on during sex’. Jim responds dismissively ‘But I couldn’t use one of those things’. While thinking to himself ‘Maybe she’s got a point’. Lines like ‘It’s just everyone is at risk now, even you and me!’ regarding AIDS and ‘But I couldn’t use one of those things. Nobody uses those things anymore!’ regarding condoms attracted criticism. Both these lines were objected to not only on the grounds of accuracy but also in reference to the emotions they would likely elicit in the intended audience. To the idea that ‘everyone is at risk’, one commentator objected ‘no this is not so’, while another queried ‘might this scare people more than is justified?’.Similarly, Herein lay a tension; through authentically depicting familiar teenage anxieties, producers hoped to make the text salient and to address teenage fears, offering a realistic representation of condom negotiation through the cartoon script. But it was also felt that if enough space were not given to vital discussions of condom use, negotiation, and AIDS in the cartoon, then representations of these fears might potentially normalise myths. It was feared that by authentically portraying the mistaken attitudes towards AIDS and condoms circulating within teenage sexual culture, such attitudes would be proliferated. Belfield, annotating the first draft, wrote ‘The script seems to only focus on use of condoms, there is nothing on communication, yet the title suggests talk more’, Belfield repeated these thoughts later with a less expansive ‘how about suggesting more communication?’While ultimately Jim and Sylvia decide they will use a condom if they have sex, this decision takes place with their friends, rather than one another. When Sylvia requests the use of condoms during sex, Jim initially dismisses it, then goes on to discuss condoms with his friend Steve, while Sylvia discusses their use with her friend Jane. Jane and Steve are having safer sex together and so share the knowledge of their sexual relationship and condom use with their friends, but separately, rather than as a group despite this mutual friendship. In the end, it is not Sylvia who convinces Jim to use a condom in the future, but Steve, who appeals to Jim’s sense of masculinity by arguing condom use is ‘the real man thing to do these days’ to persuade him .83you know that’s not true. You’re just taking care .’ This exchange, presenting the responsibility for condom use as shared while sympathetically acknowledging teenage girls’ fears about accusations of promiscuity, is fairly typical of adolescent entertainment media’s representations of condom negotiations. While the DHSS and HEA would favour narratives that accused teenage girls who did not practise safer sex of cowardice and complacency, running adverts with taglines like ‘AIDS – You’re as safe as you want to be’ across the late 1980s, teenage magazines took a more feminist track from as early as 1983.In contrast, when Sylvia explains to Jane ‘Jim doesn’t want to use condoms but I’m not going to have sex with him till he agrees. It’s the only way to be safe’, Jane responds by framing condom use as an act of care—‘He will if he cares enough for you’—not dependent on gender and suggests Sylvia take responsibility for the provision of condoms: ‘You’d better carry a packet of condoms with you just in case’. To this Sylvia responds ‘But he’ll think I’m sleeping around’, so Jane attempts to reassure her, repeating the idea that it is an act of ‘care’ with ‘Well only be achieved safely within a loving relationship and with the ‘right’ person who had to be sought. This was achieved by presenting love as a rare but vital component of safer sex, teenage first-sex as deeply meaningful, and by repeatedly constructing condom use as a care act.Here it is worth unpacking the intent behind the deployment of the concepts of ‘love’ and ‘care’—or loving carefully—in the context of adolescent sexuality and public health education. Positioning condom use as an act of care or love is a reoccurring technique in safer-sex and HIV/AIDS health education initiatives. While the Terrence Higgins Trust and Gay Men Fighting AIDS attempted to normalise condom use between men through eroticising safer sex in their health promotion materials, as well as associating it with care,Love Carefully and their ongoing Men Too campaign,Despite this scene that addressed the fears many young women felt around condom use, the more dominant narrative of condoms as distasteful and somehow connected to masculinity caused consternation among reviewers of the first draft. Indeed, Helen Martins, the FPA’s publications officer, questioned the framing of condom use within the leaflet as a whole, asking ‘will young women feel they are equally a target audience for this …’. The use of appeals to masculinity garnered further criticism later when the FPA flagged similarities between Love Carefully’s introduction and cartoon script were circulated, this time with the accompanying images, FPA commentators framed their annotations with a chastisement ‘Please see all the general and specific comments made on earlier draft: most of these still apply, so have not been repeated here’.When photocopies of the second draft of Similar expressions of distaste frame the suggested image that was proposed to accompany this scene ; the annBoth these lines were changed in the final published version of the cartoon. Jim expressing his ‘love’ (rather than ‘like’) for Sylvia in conversation with Steve, and Steve saying condom use is the only way ‘to protect us all’ rather than merely ‘us’ . These cLove Carefully, especially those making reference to the tone of the cartoon, particularly the proposed final lines. The first draft of the cartoon ended with Sylvia’s enthusiastic final line ‘Oh that’s great Jim, you really do care’ in response to Jim’s agreement to use a condom. To which it was proposed, he brightly respond ‘Nothing’s going to spoil this romance’. Service, pulling no punches in the knowledge that his response would be understood as having humorous intent, underlined this final line and wrote ‘Yuk!’, while another commentator sarcastically wrote ‘Strong stuff!’. We can read sarcasm and humour off the page here by placing these directionless comments in the context of the more sensible actionable criticism discussed earlier, which offered suggestions for additions or changes, drawing attention to elements of the text, which might be problematic or misconstrued.Despite ongoing tensions regarding who should deliver AIDS education to teenagers, particularly where condom use was central in the text, relations between Brook and the FPA were dominated by shared goals, similar visions of teenage identity and mutual respect. This shared vision of the world, and how to change it, is at its most obvious in the traces of humour, which can be found in the archive. It is detectable in the humorous letters sent between Brook and FPA members of the OSPGLove Carefully to imagine a discerning teenage reader finding the line equally sickly and consequently ignoring the safer-sex message in response to the insincerity of the final exchange. In the second draft, an amendment was proposed, ending Sylvia’s line ‘Oh that’s great Jim you really do care. Till then, there’s always kissing and hugging and stroking … ’, which was responded to by one commenter with ‘bit twee?’. The final draft of the cartoon had the line return to the original ‘Yuk!’ formation, the ‘twee’ suggestions of other pleasure-seeking non-penetrative sexual activities left out.It is significant that the lines ‘Oh that’s great Jim, you really do care’ and the responding ‘Nothing’s going to spoil this romance’ were read as too saccharine by commenters. The implication behind the comment directing the producers behind Love Carefully’s shortcomings as a text and to the wider cultural context, which prevented those involved in the sex education of teenagers from delivering texts that had bite. Jokes, even those in-jokes made within an intimate closed circle such as that between Brook’s OSPG and the FPA’s AWG, hold significance beyond the indication of shared humour or the existence of an emotional community. As Mary Douglas argues, jokes are ‘a victorious tilting of uncontrol against control, … the levelling of hierarchy, the triumph of intimacy over formality, of unofficial values over official ones’.other. Brook and the FPA’s shared jokes established them as a group of like-minded peers battling the sex education policy, which would silence their efforts and refute the ideals that they based their interventions on –teenagers as agents, sexual knowledge as a good.This shared sense of humour demonstrates an empathetic relationship between the two organisations, the existence of an emotional community of adults organised around a shared desire to take the needs and experiences of adolescents seriously. The sarcasm and silliness here acts to chastise ‘insincerity, pomposity, stupidity’,The significance of this buoyant emotional community of AIDS educators, intent on the empowerment of adolescents lies in the ways it differs from other communities of AIDS education producers. Those who saw children and adolescents as innocents in need of protection viewed the threat of AIDS with some combination of panic over the potential spread of the disease, and anxiety over the potentially damaging effects of providing sex education to the uninitiated. Theirs was a community of pessimism and reluctance; viewing the sex education of adolescents as at worst a damaging incursion upon the rights of parents and innocence of children, and at best a necessary evil (rather than liberating good). While the DES blocked attempts to include explicit content in school materials and the BMA produced an AIDS board game that avoided discussing sex,Love Carefully.Despite shared ideals, not all criticisms were taken on board, indeed many aspects of the first draft that had caused consternation made it into the final draft. For instance, the term ‘AIDS virus’ rather than ‘HIV’ was used with little clarification despite being flagged several times for its inaccuracy and the narrative of inevitable decline towards AIDS it implied. Here the clarity of the message ‘use a condom’ was favoured over the opportunity to clarify the trajectory of HIV. This change, from AIDS to HIV, would only be made in the second edition of Love Carefully. Oral sex, and the risks it might potentially carry, also went unexamined despite requests on draft two for its inclusion. Given these omissions and shortcomings, we might ask if the triumphant press release produced for Love Carefully can really make the claim that the leaflet adequately suggested ‘ways of raising the AIDS issue and discussing condom use’? Especially we might question if its aim to ‘help young people, particularly young women, develop the assertion skills’ was fulfilled? As Belfield asked, would young women ‘feel they are equally a target audience’ for the finished product?While changes in tone and language were made during the drafting process, the cartoon text maintained its gendered narrative of male reluctance to use condoms and female fear of AIDS. Moreover, the leaflet only mentioned HIV transmission between men and women despite early suggestions for a more inclusive introduction that would discuss same-sex relationships. Moreover, anal sex, which was included in the first and second draft of the introduction, was omitted from the final published edition of Just Seventeen was a hugely popular magazine and McFadyean a recognisable figure, signalling to teenage girls with her presence that the leaflet might be for them. Moreover, the production decisions borrowed heavily from teenage girls’ magazines in visual style, layout and content. The front cover of the pamphlet sported portraits of pop stars Dr Robert and Leslie & Shirlie, deployed as they would be in teen magazines, with short encouraging statements. The little smiling portrait of McFadyean is reminiscent of those which accompanied the problem pages she managed as Agony Aunt to Just Seventeen. All these layout features gave the impression that Love Carefully might be a couple of pages from a Just Seventeen, rather than a Brook production. Combined with the mix of medical and colloquial language in McFadyean’s introduction, added between the second draft and final production stages, the prose read like the health pages that were a weekly feature of Just Seventeen. The final familiar element was the cartoon strip. A mainstay of twentieth-century teen magazines, cartoon strips and photo stories was used to deliver romantic or comedic narratives and health messages in the pages of magazines like MIZZ and Just Seventeen.Penis Pack, a teaching pack on puberty designed for adolescent men with additional educational needs, it was suggested that the cartoon be removed from the context of the leaflet and used on its own, lest male teenagers be alienated by its femininity.As a finished product, shortcomings notwithstanding, the answer to these questions is yes. Penis Pack, Love Carefully enjoyed wide circulation, appearing in a variety of sex education teaching packs and reading lists alongside other publications, as well as finding its way into libraries, youth groups and universities. Such was its popularity that it was reviewed for a second edition in 1990, again with Brook circulating it amongst interested members of the FPA for comment. Again, the term ‘AIDS virus’ was raised as an issue, as was Jim’s apparent reluctance to use condoms despite their growing popularity. As with the first edition, the pressure to produce a second edition quickly was emphasised, Brook gesturing to orders for the leaflets already waiting to be filled. Changes were made to the leaflet for the second edition—the language updated and McFadyean’s biography adjusted—but these changes were limited; Brook and other sex education NGOs instead relied on the use of Love Carefully in combination with other materials to mitigate any perceived shortcomings.Beyond this heavily edited inclusion in the Sex education and adolescent sexuality were topics of fraught and involved discussions among politicians, the media, and adolescents before the AIDS crisis, and the disease catalysed no immediate loosening of tongues on the subject of sex. Policy dictated how AIDS-related media intended for the consumption of children could frame the disease, dictating who could produce it, where such material could be used and by whom. Brook, like other NGOs involved in the fight against AIDS, was subject to these dictates from on high. Brook’s efforts to educate adolescents about AIDS, safer sex and consent were stymied by the bureaucratic politics and jurisdiction battles, which inhibited the government’s own response, while an awareness of what materials, ideas and information would not be allowed within the school gates encouraged the charity to omit explicit information on anything other than heterosexual intercourse. The charity thus anticipated objections from government, parents and governors and attempted to avoid the chagrin of these unintended audiences by avoiding controversial subjects and earmarking the text for use outside schools where the rules governing what teenagers could be told were less stringent. In creating a leaflet for teenagers on safer sex, Brook imagined a group of adolescents with agency: young people who, given the right information delivered in a respectful tone which valued their relationships, would practise safer sex. The group constructed by the leaflet presented an ideal of good behaviour where relationships were presented as ultimately caring, with strong female friendships guiding girls to challenge boys to use condoms, while male friendships were shown to support a caring performance of masculinity with condom use becoming an act of love and maturity.Love Carefully, in the context of policy and practice, deploying techniques drawn from the history of emotions and literary analysis. By applying a Lacanian critique to both government sex education policy and the internal discussions of Brook and the FPA, in combination with the intertextual analysis of Love Carefully, this article revealed the ideological and emotional communities and contexts behind the text. This methodology could be applied to other didactic texts aimed at fostering positive health outcomes as a way of accessing how texts are changed by production context and authorial intent. Here the analytic traced the shared sense of anxiety, urgency, optimism and humour specific to the creation and content of Love Carefully, ultimately revealing it as representative of a genre without diminishing its unique context and content. These elements were demonstrated by following the Love Carefully leaflet through the drafting process, examining what was included and excluded from the final publication, anxiety about the inauthentic tone and worries about the framing of masculinity and condom use. This highlighted the problems that marred the production process and the awareness of those involved about the possibilities of misapprehension created by over simplification and misplaced emphasis.The article began by situating Brook’s textual response to AIDS, Love Carefully provided an engaging and sophisticated text that aped the successful style of teenage magazines. As the article argued, the production of this varied and informed text was made possible by the supportive, if fractious, emotional community that Brook could draw on. This was a community with a widening pool of knowledge, expertise and content, equipped to produce Love Carefully as a salient document, familiar to teenagers in textual tone and visual design but novel enough to capture interest and deliver its messages of safer sex and consent. Brook and theFPA were a community speaking to, and for, teenagers, agitating for teenage empowerment and self-help through condom use but also dictating that safer sex was a fundamental aspect of care.When assessing the published document,


Older respondents were less likely to answer the items correctly (β = −0.194 (95% CI: −0.333–−0.055), p < 0.01. When educating the public on the proper use of antibiotics and antibiotic resistance, multiple strategies could be considered for people from all walks of life, as well as target different age groups.Antibiotic resistance is occurring widely throughout the world and is affecting people of all ages. Socioeconomic factors, education, use of antibiotics, knowledge of antibiotics, and antibiotic resistance were assessed in four cities in Asia, namely Hong Kong, Shanghai, Hangzhou, and Bangkok. A survey using cluster sampling was used in 2021 to collect data on 642 subjects. Hongkongers used less antibiotics and were knowledgeable about using antibiotics to treat diseases, while Shanghainese were knowledgeable about antibiotic resistance. The multi-linear regression model reported that respondents who lived in Hong Kong (β = 0.744 (95% CI: 0.36–1.128), Shanghai (β = 1.65 (95% CI: 1.267–2.032), and Hangzhou (β = 1.393 (95% CI: 0.011–1.775) (reference group: Bangkok), who had higher scores on antibiotics knowledge (β = 0.161 (95% CI: 0.112–0.21)), higher educational attainment (β = 0.46 (95% CI: 0.296–0.625)), and who were more likely to consult a doctor on using antibiotics (β = 1.102 (95% CI: 0.606–1.598)), were more likely to give correct answers about antibiotic resistance,  In 2015, the World Health Organization (WHO) reported that antibiotic resistance is occurring everywhere in the world and is affecting people of all ages. . There iChina is a country where a large number of respondents reported that they had obtained antibiotics from a friend or family member . A crossIn 2011, a survey revealed that Hong Kong residents who had a low level of education and were over 60 years of age had inadequate knowledge of self-medication; with a majority believing that chronic diseases should be self-managed . LikewisIn Thailand, respondents were recently shown to be frequently unable to distinguish antibiotics from other medicines . During In Sweden, a high-income country within the North European region, 80.7% of the respondents agreed that bacteria could become resistant to antibiotics, only 19.1% had the misconception that common colds could be cured more easily using antibiotics, and most patients trusted doctors to not prescribe antibiotics . In DenmRegarding the determinants of self-medication with antibiotics in Anglo-Saxon European countries, a systematic review reported that these included position at work, employment status, and patient knowledge . AnotherCurrent evidence points out that socioeconomic, policies, and educational factors are known to play an important role in illness behaviours and antibiotics consumption. The profound differences between Eastern and Western cultures are manifested in their political systems, histories, and religions. The findings from previous studies conducted in Western countries cannot be extrapolated to Eastern cultures. The present study is designed to fill this gap in knowledge and to provide a snapshot of the current situation on the prevalence of antibiotic use in Asian countries. It is not only providing an estimate of the magnitude of the problem, but would also allow for an evaluation of the health promotion programmes on antibiotics. The main question in our study is whether demographics and city of residence can predict the knowledge and use of antibiotics in Asian countries.A total of 680 participants were reached in our study. After checking the questionnaires, 38 questionnaires were discarded because more than 10% of the items were found to be invalid. Those items were related to participants choosing more than one option or having nil replies for the questions. A total of 642 valid questionnaires were collected from the four cities. Among the valid questionnaires, 161 were from Hong Kong, 160 from Shanghai, 160 from Hangzhou, and 161 from Bangkok. The percentage of valid questionnaires was 94.4%.p < 0.001. In terms of age, 53.4% of the participants in Hong Kong were 18-30, compared to 22.5–33.8% in the other three cities. Among those in the age group of 41–55, the proportion in Hangzhou was 43.8%, compared to 12.4–23.1% in the other three cities, with p < 0.001. With regard to educational attainment, 75% of the respondents in Shanghai had a sub-degree or bachelor’s degree, compared to 44.7–57.1% in the other cities, with p < 0.001. In terms of marital status, 71.9% of the respondents in Hangzhou were married with children, compared to 25.5–44.1% in the other cities. Moreover, 63.4% of Hongkongers and 47.8% of Thais were never married, compared to 19.4–20.0% of their counterparts, with p < 0.001. For occupation, 38.8% of the Shanghainese were professionals, compared to a lesser percentage in the other three cities. Regarding economic situation, narrative descriptions were used to indicate the current financial situation of the respondents. They are used to examine subjective feeling of the participants about their current economic situation. The descriptors were from very adequate to very inadequate, as non-local readers would find it difficult to interpret monetary amounts. Thailand had the highest proportion of respondents who claimed that their economic situation was adequate, at 78.4%, compared to 23.8–42.2% of the respondents from the other cities. Half of the respondents from Hangzhou claimed that their economic situation was barely adequate, compared to 31.7–41.9% of their counterparts, with p < 0.001. With regard to religion, the majority (93.8%) of Thais were Buddhist, while 21% of the respondents from Hangzhou indicated that they were Christian. As for the number of household members, the median was 4 in Hangzhou and 3 in the other cities, with p < 0.001. Please refer to With regard to gender, the proportion of males in Shanghai was 65.6%, significantly higher than in Hong Kong (46%) and Bangkok (42.2%), with p < 0.001. As for the sources of the antibiotics that they last took, 72.3% of Thais got their antibiotics from a medical store or pharmacy, compared with 29.4–31.8% of the respondents from the other three cities. Only 8.5% of Thais got their antibiotics from a hospital or clinic, p = 0.003. Regarding whether the respondents preferred to consult a doctor who had declared that antibiotics should be used responsibly, 85.7% of Thais gave a positive response compared to less positive responses from the other respondents, with p < 0.001. When the respondents were asked whether they had brought a child aged 15 years old or below to consult a doctor in the past 12 months and asked for antibiotics, 70.6% of Thais responded in the affirmative, compared to 16.7–38.6% of the other respondents, with p < 0.001. Please refer to With regard to the use of antibiotics, nearly half of the respondents in Hangzhou and Shanghai had taken antibiotics in the past 6 months, compared with the Hongkongers and Thais who were using less antibiotics, with The participants were asked which of 12 medical conditions could be treated with antibiotics. Among the list of diseases, only wound infections, gonorrhoea, and urinary tract infections can be treated with antibiotics. The median for items that were answered correctly by Hongkongers was 7, with an interquartile range of 4–9, compared to a median of 5 for the respondents from the other three cities.When the individual items were examined, a large proportion (72.7%) of Thais thought that human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) could be treated with antibiotics. With regard to gonorrhoea, more than 70% of the respondents from Hong Kong and Hangzhou mistakenly answered that the disease could not be treated with antibiotics; while for bladder or urinary tract infection (UTI), the majority of the respondents identified the answer correctly, with the exception being those in Hangzhou, where 53.1% gave the wrong answer. For wound and skin infections, more than 80% of Shanghainese and Hongkongers identified the correct answer, a higher proportion than their counterparts. Please refer to The respondents were asked whether the eight statements about antibiotic resistance were “true” or “false”. Items 2, 3, 4, and 8 were true, while the remaining items were false. A large proportion of respondents from Hong Kong and Shanghai responded correctly to item 2 (“Many infections are becoming increasingly resistant to treatment by antibiotics”) and item 8 . For item 5 (“Antibiotic resistance is an issue in other countries but not here”), 79.4% of the Shanghainese correctly identified this as a false statement compared with a lesser percentage in the other three cities. The median for items that were answered correctly by Shanghainese was 5, with an interquartile range of 4–6, compared to the same median, with an interquartile range of 3–6 for the respondents from Hangzhou, while the Thais and Hongkongers achieved a median of 3 and 4, respectively. Please refer to 2 was 0.282. The model was able to explain 28.2% of the variance in the outcome by the significant variables. Please refer to A multiple linear regression was applied to identify the predictors of knowledge about antibiotic resistance. The potential determinants were based on previous literature about factors that are causing the associations between antibiotics use and antibiotics resistance. The dependent variable was the total number of correct items on antibiotic resistance, while the independent variables included the total scores for knowledge of antibiotic use, city of residence, educational attainment, economic situation, whether to consult doctors on using antibiotics, to consult a doctor before using antibiotics, accommodation, marital status, and gender. All the above variables were included in the regression analysis. A stepwise elimination procedure was used to eliminate the insignificant variables. There were five variables left in the final model. The model showed that respondents who lived in Hong Kong, Shanghai, Hangzhou (reference group: Bangkok), who had higher scores on antibiotics knowledge, a higher level of educational attainment, and who were more likely to consult a doctor on using antibiotics were more likely to give correct answers about antibiotic resistance. Responders who were elderly were less likely to answer the items correctly. The adjusted RFor the city fixed effects regression model, in Hong Kong the predictors include educational attainment, consulting a doctor about using antibiotics, and the score on knowledge of antibiotics. The adjusted R-square is 0.204. Please refer to In Shanghai, the predictors include educational attainment and total score on knowledge of antibiotics. The adjusted R-square is 0.106. Please refer to For Hangzhou, the predictors include age group, total score on knowledge of antibiotics, consulting a doctor about using antibiotics, and educational attainment. The adjusted R-square is 0.308. Please refer to For Bangkok, the predictors include the total score on knowledge of antibiotics, educational attainment, and consulting a doctor about using antibiotics. The adjusted R-square is 0.249. Please refer to Inappropriate use of antibiotics due to inadequate knowledge and inappropriate behaviours are alarming problems in most countries in the world. Antibiotic resistance is an abstract concept for community dwellers, who may have little knowledge about biology, bacteria, and infection compared to healthcare professionals . Our resIn this study, we classified Shanghai and Hong Kong as high-income cities. According to China Daily, Shanghai was ranked first among cities in China, with the highest per capita GDP in China in 2019 , while HHongkongers used fewer antibiotics in the past six months compared with respondents from the other three cities. According to legislation, in Hong Kong antibiotics can only be obtained from a pharmacy with a doctor’s prescription . In addiRegarding specific knowledge on the conditions or diseases that can be treated with antibiotics, other than Hongkongers most respondents incorrectly believed that antibiotics could be used to treat HIV/AIDS. That the Hong Kong respondents were better informed on this point could be related to their higher level of educational attainment, with 19.3% having attained a bachelor’s degree or above. Antibiotics cannot be used to treat HIV/AIDS; however, with prudent use, antibiotics can reduce early mortality in HIV-infected adults and children on antiretroviral therapy . For theFor antibiotic resistance, the median of the correct answers ranged from 3 to 5 among the respondents in the four cities. Unlike knowledge of antibiotics, antibiotic resistance is considered an abstract issue by people from non-healthcare disciplines. A large proportion of the respondents mistakenly identified the following as a true statement: “Antibiotic resistance occurs when your body becomes resistant to antibiotics and they no longer work as well”. According to the World Health Organization, antimicrobial resistance implies that antibiotics become less effective and infections become increasingly difficult or impossible to treat . The larThe results of the regression analysis in the present study showed that respondents who lived in Hong Kong, Shanghai, and Hangzhou (reference group: Bangkok), who had a higher level of educational attainment, and who consulted doctor about using antibiotics were likely to give more correct answers, while older respondents were less likely to give correct answers on antibiotic resistance. For the city fixed regression model, educational attainment and knowledge on antibiotic use are predictors among the four cities. The above associations imply that socioeconomic status, living cities, and knowledge on antibiotic use are contributing to knowledge about antibiotic resistance. A study conducted in Hong Kong in 2012  showed tConsistent with recent studies conducted in Asia, the US, and Norway ,34,35, oOlder people were less likely to give correct responses on antibiotic resistance. In one Asian country, the majority of the older adults incorrectly believed that antibiotic resistance occurs when the body becomes resistant to antibiotics . About 7There are limitations to this study, which should be taken into account. First, although quota sampling was used in the four cities, non-random sampling was used to recruit subjects in each stratum within the cities. Second, the cross-sectional design of the study made it impossible to determine the cause and effect of the study variables. In future studies, representative samples stratified by region should be collected to further analyse antibiotic use and knowledge in moderate and high-income cities.A quantitative cross-sectional survey was used for the study. The data collection period was from January to August 2021.The participants were recruited from the urban areas of Shanghai and Hangzhou in China, Bangkok in Thailand, and the Hong Kong Special Administrative Region of China. These four cities were selected because they represent high and middle-income populations in Asia. Quota sampling was used in the study to uphold the representativeness of the study sample. The co-investigators of the respective cities identified the population strata , and determined how many participants were to be recruited from each district in the community. Convenience sampling was used in each stratum for subject recruitment. The questionnaires were uploaded to an online survey system. Each computer account could submit the questionnaire only once. The co-investigators of each city were responsible for downloading the questionnaire data. The participants were not compensated for their time in this study.Persons 18–65 years old, who had been taking medicine and using antibiotics in the past 12 months, who had a job, and who were able to read and communicate in the local language were eligible for participation. People who were cognitively impaired and unable to communicate in the local language were excluded.p = 0.50 to produce the most conservative estimate of the sampling error. With a confidence level of 95% and a margin of error of 0.05, a sample size of no less than 385 would be required [It was estimated that a sample size of 601 would be required for this study. This estimate was based on the proportion of the population that was thought to take antibiotics. The standard deviation of the unknown prevalence is required to calculate the size of a sample. As the proportion (p) was unknown, a conservative estimate was set at required . For a lZ = Z statistic for a level of confidenceP = expected prevalence or proportion d = precision Data were collected using a questionnaire. The questionnaires were delivered online, due to the COVID-19 pandemic. The questionnaires that were returned were treated as anonymous.Questionnaire for Data CollectionThere were two sections in the questionnaire. The first section examined the participants’ use of antibiotics, and their knowledge of antibiotics and antibiotic resistance. The second section, which was developed by the researchers, was for collecting data on demographic characteristics.Antibiotic Resistance: Multi-Country Public Awareness SurveyThe questionnaire developed by the WHO for conducting a multi-country public awareness survey on antibiotic resistance was adopted in this study. The survey tool was developed by a specialised research agency, in collaboration with the WHO. A field test was carried out by the research agency before data were actually collected . The oriThe questionnaire used in this study was developed based on the above Cantonese Chinese scale by the Centre for Health Protection, Hong Kong. The scale used in this study was a shorter version of the original questionnaire, incorporating the questions related to the general public’s understanding of the effect of antibiotic use, their attitudes and practices on antibiotic use, and their knowledge and awareness of the problem of antimicrobial resistance. For a test of the content validity test of the scale, five healthcare experts were invited to determine the relevance of the items in the scale. All of the items were considered appropriate for the present study. Cohen’s kappa was calculated for each item to determine the reliability of the scale. Cohen has suggested that inter-rater agreement is substantial if the kappa is between 0.61 and 0.80 . The weiThe newly developed scale was translated into Simplified Chinese and Thai and underwent validity and reliability tests in China and Bangkok before data were collected. Approvals for the adoption of the scales were obtained from the World Health Organization and Centre for Health Protection, Hong Kong.Demographic CharacteristicsData that were collected on the demographic characteristics of the respondents included information on their age group, gender, financial situation, level of education, number of household members, and so on.The study was started in June 2020 and completed in August 2021. It was conducted during the COVID-19 pandemic. Online subject recruitment was used instead of the face-to-face approach. The co-investigators may not be able to explain the questionnaires resulting in some invalid data.p-value of <0.05 was considered statistically significant.A statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 . Data on demographics, the use of antibiotics, knowledge of antibiotics and antibiotic resistance were put through a descriptive analysis. A one-way analysis of variance (ANOVA) or Kruskal–Wallis test was used to determine the statistically significant differences between the participants in the four cities. Multiple linear regression was used to determine the demographic and social predictors of knowledge of antibiotic resistance. A The present study showed that people in middle-income cities such as Hangzhou and Bangkok used more antibiotics. Hong Kong people had more knowledge of antibiotics, which could be related to a higher level of educational attainment. On questions about diseases that can be treated with antibiotics, gonorrhoea was the disease that was least likely to receive a correct answer. In general, people with more knowledge about antibiotic use were more likely to give correct answers about antibiotic resistance. Respondents who lived in Hong Kong, Shanghai, and Hangzhou (reference group: Bangkok), who had a higher level of educational attainment, and who were more likely to have consulted a doctor about using antibiotics were more likely to give correct answers on antibiotic resistance, whilst older respondents were less likely to give correct answers on antibiotic resistance. When educating the public on the proper use of antibiotics and antibiotic resistance, the strategies that are employed should be multifaceted and focus on both long-term and short-term outcomes.


MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution.Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (< 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM.p-value < 0.05).Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC. Approximately one third of head and neck squamous cell carcinoma (HNSCC) originate in the oral cavity (OSCC) . For patth edition of the AJCC that provides a clear definition for DOI  is a strong predictor for occult LNM, this cutoff value is therefore used within the Erasmus MC in making decisions on END , 3, 4. T mm is a  for DOI .In some centers, sentinel lymph node biopsy (SLNB) is being performed to rule out the presence of occult LNM. With detection rates of 95% –12, 0.93It is clear, that there still is a need for reliable preoperative predictors of occult LNM that can further improve the decision making process on END. Ideally, such predictors should be easily incorporated in a routine diagnostic setting.MET orchestrates the program of invasive growth  in early oral tongue SCC (OTSCC). This association was compared with DOI > 4 mm, a known predictor of occult LNM. We further, hypothesized on the potential added value of MET positivity in the clinical decision-making on END.Human tissues and patient data were used according to “The Code of Conduct for Responsible Use” and “The Code of Conduct for Health Research” as stated by the Federation of Dutch Medical Scientific Societies . FurtherInclusion criteria were patients with early OTSCC (pT1-2) treated primary with surgery with a neck dissection, at the Leiden University Medical Center  and the Erasmus MC Cancer Institute .All patient and tumor characteristics, except the DOI, were retrieved from the patient files including: gender, age, tumor diameter (cm), TNM , extranoFollow-up data in respect to OS and DFS were also recorded.A previous history of head and neck cancer was a reason for exclusion.Formalin-fixed paraffin-embedded tissue blocks representative of the included cancers were retrieved from the tissue banks of the departments of pathology from both medical centers. Using a microtome, 3 µm thick whole tissue sections were cut for immunohistochemical analyses.®; Danvers, MA, USA) was used to detect C-terminal MET immunoreactivity according to the method described in our previous publications  is associated with histopathologically proven LNM (cN0/pN+ and cN+/pN+) and occult LNM (cN0/pN+) using receiver operating characteristic (ROC) curve analysis .The DOI cutoff value > 4 mm used in the Erasmus MC as an indication for END, was investigated by assessing the association between DOI > 4 mm and proven as well as occult LNM using ROC curve analysis .The Chi-squared test, non-parametric Fisher’s exact test and independent-Samples T-test were used to compare the patient and tumor characteristics of the LUMC and Erasmus MC cohorts.To calculate the proportion of MET positive cancers within the whole pN+ group (occult and overt LNM), the Chi-squared test was used. The same was done for DOI > 4 mm.To calculate the proportion of MET positive cancers within the occult LNM group (cN0/pN+), the Chi-squared test was used. The same was done for DOI > 4 mm.Binary logistic regression was performed to investigate whether MET positivity and/or DOI have a—joint—effect on LNM.p-value <0.05.Calculations were performed with SPSS Statistics . Unless otherwise mentioned, statistical significance was set at The 102 patients included in this study were treated for primary pT1-2 OTSCC with surgery and—if indicated—postoperative radiotherapy in the LUMC or Erasmus MC across different periods. Twenty-five (24.5%) patients were treated in the LUMC and 77 (75.5%) in the Erasmus MC. Comparison of the patient and tumor characteristics as well as MET positivity shows that there are no differences between the two centers (Hundred and two (102) patients were treated with tumor resection and a neck dissection. Thirty (29.4%) were pN+, of which 20 (66.7%) were cN0 and therefore occult metastases Table 1.ROC curve analyses showed that MET positivity is associated with pN+ and occult LNM and that DOI > 4 mm has a higher sensitivity for pN+ and occult LNM compared to MET positivity (Forty-five (44.1%) of the included cancers were positive for MET Table 2.p-value < 0.05; p-value < 0.05; p-value = 0.15; p-value = 0.19; Univariable binary logistic regression showed that MET positivity is associated with pN+ status in general , depicting the number of cancers either negative (< 10% uniform positivity) or positive for MET versus DOI ≤ or > 4 mm, illustrates that there were 2 (6.67%) MET negative cancers with LNM in the group DOI ≤ 4 mm. Three (10.0%) cancers with LNM were MET positive and had a DOI ≤ 4 mm. Eight (26.7%) cancers with LNM were MET negative and had a DOI > 4 mm. Seventeen (56.7%) cancers with LNM were MET positive and had a DOI > 4 mm Table 6.For patients with early OSCC, END is generally recommended when the chance of occult lymph node metastasis is more than 20% , 24–26. The current study shows that MET positivity is univariably associated with LNM in OTSCC. This result was expected given the established association of MET positivity with OS and DFS in OSCC , 23. TheMET gene product is more sensitive in the detection of occult LNM compared to cytokeratins in OSCC . Although DOI > 4 mm did not significantly contribute to the multivariable model, it showed a strong relation with pN+ LNM  and occult LNM . The lack of significance of DOI > 4 mm can probably be explained by the low number of cases with DOI ≤ 4mm. These results suggest that MET positivity might also be of value in predicting the presence or absence of occult LNM in the preoperative setting, and besides DOI, in the postoperative setting  in early OTSCC.The PPV of MET on occult LNM was 36.8%, which meets the recommendation of performing an END if the risk of occult LNM is 20% (NPV 80%) , in accoWe foresee that performing routine immunohistochemistry using the D1C2 antibody against the C-terminus of MET on biopsies, could be of great value in deciding when and when not to perform an END during the initial OTSCC surgery. This would improve logistics, cost-effectiveness, and would reduce patient morbidity caused by two separate surgeries. This study is performed on whole tissue sections, therefore efforts have to be made to design a future study to extrapolate these results to biopsies. To anticipate for cancer heterogeneity we expect that (preoperative) biopsies will need to be taken from the center and periphery of the cancer .The fact that there were less occult LNMs for cancers negative for MET and with DOI ≤ 4 mm compared to cancers positive for MET and with DOI ≤ 4 mm, illustrates that MET positivity could be of added value to DOI ≤ 4 mm for the clinical decision on the treatment of the cN0 neck i.e., whether regular follow-up, watchful waiting, or END is more appropriate. We can imagine that patients with MET positive cancers and DOI ≤ 4 mm could have more stringent follow-up than patients in the same DOI group but with MET negative cancers. We realize that this statement is based on very low numbers and independent validation is necessary.Taking into account that the obtained results are preliminary and need to be independently validated in a larger and more recent patient cohort incorporating both patients that underwent END and watchful waiting and containing detailed registration of relevant histopathological parameters, we believe that MET positivity could be of added value in pre- and postoperative (after primary tumor resection) decision making on END in early OTSCC.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Human tissues and patient data were used according to “The Code of Conduct for Responsible Use” and “The Code of Conduct for Health Research” as stated by the Federation of Dutch Medical Scientific Societies. Furthermore, The Erasmus MC Medical Ethics Committee approved the research protocol (MEC-2016-751).MD: conceptualization, methodology, software, formal analysis, data curation, writing—original draft, and visualization. BV: investigation, data curation, writing—review and editing, and visualization. QV: data curation and writing—review and editing. YA: data curation and writing—review and editing. SW: writing—review and editing. MW: methodology and writing—review and editing. RB: writing—review and editing. LL: writing—review and editing. SK: conceptualization, methodology, writing—review and editing, and supervision. JH: conceptualization, methodology, writing—review and editing, and supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Perfobond rib (PBL) shear connectors, made up of the perforated steel plates with the penetrating rebars passing through the holes, are extensively adopted in steel-concrete composite structures for their excellent performance. The adequate understanding of mechanical properties for PBL connectors is of great significance for their reasonable design. In this study, a push out experiment, including 12 specimens with the parameters of concrete strength, diameter of penetrating rebars and the number of holes on perforated steel plate, was performed to explore the mechanical behavior of PBL connectors with steel fiber high strength concrete (SFHSC). The experimental results showed that the shear capacity of the PBL connectors increased with the increase in concrete strength, diameter of the penetrating rebars and the number of holes. Furthermore, a general prediction formula for the shear capacity of PBL connectors was developed, which considers the shear contribution of concrete dowels, concrete end-bearing, interfacial bonding between the perforated steel plates and concrete and the penetrating rebars as well as the enhancement effect of steel fibers. The prediction results of the equation are in good agreement with the experimental data and could provide a reference for the design of PBL connectors. The use of steel-concrete composite structures in civil engineering has seen rapid growth in the past decades due to their excellent mechanical properties, convenient construction performance and outstanding economic features . In ordeTo date, the exploration for the mechanical behavior of PBL connectors with conventional concrete have been executed based on push out tests. Oguejiofor and Hosain  reportedIn recent years, various problems have been identified in the service of PBL connectors with conventional concrete. Specifically, it is difficult to ensure the casting quality of coarse aggregate concrete in the joint area during the construction process. In addition, the shrinkage of conventional concrete can result in the segregation between the steel plate and concrete . These pWith the application of UHPC in PBL connectors, some problems have been gradually discovered. The construction process of UHPC materials is complicated, which is not conducive to large-scale preparation at construction sites . In addiEven though numerous studies have been conducted on PBL connectors, there are still many problems to be solved. The experimental studies on the mechanical properties of PBL connectors are mostly focused on the specimens adopting conventional concrete or UHPC ,26, whilTo investigate the mechanical properties of PBL connectors with SFHSC, 12 push out specimens, with the variable parameters of concrete strength, diameter of the penetrating rebars and number of holes, were designed and tested. At first, the failure modes and the characteristics of the load-slip curves of the PBL connectors with SFHSC were analyzed. Afterwards, the influence of each specimen parameter on the mechanical properties of the connectors, include shear capacity, ductility and shear stiffness, was discussed based on the test results. Finally, a general equation for calculating the shear capacity of PBL connectors was established. The proposed equation fully considers the shear contributions of concrete dowels, concrete end-bearing, interface bond between perforated steel plates and concrete and penetrating rebars, as well as the reinforcing effect of the steel fibers. Furthermore, the validation for the accuracy and applicability of the equation was performed.d) includes 12, 16 and 20 mm. The specific labels and parameters of each specimen were summarized in In order to investigate the mechanical properties of PBL connectors with SFHSC in depth, the push out test including 12 specimens was conducted and the variable parameters consist of concrete strength, diameter of penetrating rebars and the number of holes on perforated steel plates. The specimens adopted in this study were designed on the basis of Eurocode 4  as depicfcu) and elastic modulus (Ec) of concrete was determined from concrete cubic tests after the standard 28 day setting as displayed in For all specimens, the Q345D structural steel with a thickness of 10 mm was adopted for the perforated steel plates and H-beams, and had the nominal yield strength, ultimate strength and elastic modulus of 345 MPa, 470 MPa and 209 GPa, respectively. The specimens were reinforced with HRB400 steel bars whose yield strength, ultimate strength and elastic modulus were 400 MPa, 570 MPa and 200 GPa, respectively. At the same time of each specimen was fabricated, three concrete cubic blocks with specifications of 150 mm × 150 mm × 150 mm were poured and cured. The real cubic strength  Plastic stage. The stress in the specimen gradually increased with the increase of load. The cracks in concrete gradually developed, and the stiffness of the connectors decreased, resulting in a reduction in the slope of load-slip curve. At this time, the outer surface of concrete and the junction of H-beam and concrete slab began to crack; (3) Yield strengthening stage. As the load increased, the growth rate of load-slip curve decreased further. Due to the high strength and good ductility of C80 concrete, cracks were almost no longer developed. There was a degree of deformation in the penetrating rebars and perforated steel plates under the action of shear force, and the stiffness of the connector was correspondingly reduced. Furthermore, this stage lasted for a long time due to the good ductility of the penetrating rebars and perforated steel plates, as well as the bonding force between steel fibers and concrete. (4) Failure stage. When the load reached the ultimate value, the PBL connector failed and the load-slip curve decreased rapidly. Corresponding to Specimen C80-D12-N3, the failure mode is the shear fracture of penetrating rebars accompanied by the crushing of concrete dowels.The relative slip between the H-beam and concrete slab was generated as the load increased, which was collected by four LVDTs in this test. Taking the load-slip curve of Specimen C80-D12-N3 displayed in Pmax and Prk denote the maximum load and characteristic load of ductility (Prk = 0.9 Pmax), respectively, and δmax and δrk denote the corresponding relative slip, respectively, in which δrk was the index to reflect the ductility of connectors. In addition, Ks denotes the shear stiffness of the PBL connectors in the initial loading stage. As displayed in Ks is specified as the slope of the connection between the origin and point A that corresponds to a relative slip of 0.2 mm, and points B and C were determined by Pmax and Prk, respectively.The test results of all the specimens in this test were summarized with reference to Eurocode 4  as preseThe load-slip curves of Specimens C50-D12-N2, C80-D12-N2 and C100-D12-N2 are shown in A noteworthy phenomenon observed in this test as shown in The load-slip curves of specimens with C80 concrete and 2/3 holes on perforated steel plates, as depicted in The load-slip curves of Specimens C80-D12-N1, C80-D12-N2 and C80-D12-N3 are shown in The reasonable prediction for the shear capacity of PBL connectors through theoretical calculation is a prerequisite for their rational design in practical engineering. Until now, various scholars have proposed formulas for predicting the shear capacity for PBL connectors. In this section, four representative formulas, respectively, proposed are summarized in Vcu) based on Equations (1)–(4) and the experimental data, as displayed in It can be observed from the comparisons of prediction results .The shear capacity of PBL connectors is mainly contributed by concrete dowels, concrete end-bearing, interface bond between perforated steel plates and concrete and penetrating rebars, in which the effect of steel fibers could be reflected in the former three contributions. Thus, the formula for shear capacity could be generally expressed as:fcs denotes the shear strength of the concrete under multiaxial stresses (MPa) and can be calculated by fcs = 0.25fc, in which fc denotes the prismatic strength of the concrete and can be obtained by fc = 0.8fcu; and Acd denotes the sectional area of the concrete dowel (mm2).When the PBL connector is subjected to shear force, the concrete dowels would be subjected to the pressure of the steel plates, penetrating rebars and adjacent concrete at the same time, causing a quite complex force state . The conψ1 as:The shear strength of the concrete dowels in PBL connector is increased due to the action of external pressure , thus thKf1 which is related to the volume content, length and diameter of fiber [ψ2 is the coefficient to be determined.As mentioned in of fiber .(8)Kf1=Finally, the contribution of the concrete dowels containing steel fibers to the shear capacity can be obtained as:Aeb denotes the contact area between the steel plate and concrete (mm2).The concrete located at the end of perforated steel plates is able to provide a portion of the shear strength of the PBL connectors. The anti-shear contribution is determined by the contact area between the perforated steel plates and concrete, as well as the compressive strength of the concrete. Consequently, the shear resistance of the concrete end-bearing can be expressed as:Veb can be further expressed by adopting the strength enhancement factor as:Similar to the calculation of the shear contribution of concrete dowels, considering the pressure of the surrounding concrete and the strengthening effect of the steel fibers on the strength of concrete end-bearing, here Consequently, the contribution of concrete dowels and concrete end-bearing can be combined as:fb denotes the bond strength between the perforated steel plates and concrete (MPa), which is related to the square root of the concrete compressive strength as [ψ3 is the correlation coefficient to be determined.The perforated steel plates could contribute to the shear capacity of the PBL connector by means of the bond between it and the nearby concrete, and the contribution is related to the contact area and bond strength between the steel plates and concrete, which can be formulated as:ength as :(14)fb=ψKf2 is introduced like Kf1 to reflect the effect as [ψ4 is the coefficient to be determined.Just as the enhancement influence of steel fibers on the shear capacity of concrete dowels, steel fibers also have an enhancement effect on the bond strength between the perforated steel plates and concrete, thus the enhancement factor ffect as :(15)Kf2=In the end, the contribution of the interface bond to the shear capacity of the PBL connector is:Apr denotes the cross-sectional area of penetrating rebar (mm2); and fs denotes the shear strength of penetrating rebar (MPa), which can be expressed by fs = fy/The penetrating rebars are subjected to both bending moment and shear force in the working phase. According to existing studies, the shear resistance of the penetrating rebars is not affected by the concrete strength as well as the steel fibers, and is only related to the shear strength and cross-sectional area of the rebars . Therefoψ5 to be determined to reflect this effect as [Furthermore, there would be shear deformation in the penetrating rebars after the force is applied, and the concrete in the deformation direction of the rebars can prevent their further deformation to enhance the shear capacity of the connectors. It can be speculated that the degree of enhancement to the shear capacity on the penetrating rebars is related to the deformation degree of rebars, hence it is reasonable to introduce a coefficient ffect as :(18)Vpr=ψ1, ψ2, ψ3, ψ4 and ψ5 are the coefficients to be determined by experiment data.Ultimately, the calculation equation for the shear capacity of PBL connectors can be established as follows, where ψ1, ψ2, ψ3, ψ4 and ψ5 can be obtained as 1.205, 0.427, 0.016, 1.056 and 3.037, respectively. Accordingly, the shear capacity of the PBL connectors with SFHSC can be derived as:After the regression analysis was performed, the values of the coefficients The prediction results based on Equation (20) for the shear capacity of each specimen in this study are presented in (1)PBL connectors employing SFHSC primarily experience one or more of the failure modes of concrete dowel crushing, penetration reinforcement fracture and steel plate yielding, while essentially no severe cracking of the concrete slab occurs, which may appear in the PBL connectors employing conventional concrete. Moreover, as shear failure of the penetrating reinforcement occurs, it is often accompanied by failure of the concrete dowel. The full load carrying capacity of the member that does not fail is not fully utilized when the connector fails, and the desirable design is that the concrete dowel, the penetrating rebars, the steel plate and the concrete slab all achieve their full load carrying capacity.(2)The shear capacity of PBL connectors increases with the increase in concrete strength, diameter of penetrating reinforcement and number of holes and the influence degree of the change in the number of holes is the most significant. In the design, the increase of these parameters is effective in increasing the shear capacity of the connectors. The continuous growth of these parameters cannot bring a constant and significant increase in the shear capacity of PBL connectors, and the mutual adaptation of the parameters of PBL connectors should be ensured in the design process. Additionally, the random distribution of steel fibers in concrete can effectively inhibit the expansion of old cracks and the formation of new cracks, and then enhance the ductility and shear capacity of the specimens.(3)One general prediction formula for the shear capacity of PBL connectors was established based on regression analysis of test data. The proposed formula accounts for the contribution of concrete dowels, concrete end-bearing, interface bond between perforated steel plates and concrete and penetrating rebars to the shear capacity of the PBL connectors, as well as the reinforcing effect of the steel fibers on the material properties. The comparison of the prediction results obtained using the proposed formula with the experimental results demonstrates the excellent accuracy and applicability of the proposed formula, which can be used for the prediction of the shear capacity and provide a reference for the design of PBL connectors.This paper focuses on the study of the shear performance of PBL connectors applying SFHSC. With concrete strength, diameter of penetrating rebar and number of holes of PBL connectors being considered, 12 specimens were designed and tested, based on which the parameter influence mechanism was explored and the shear capacity equation for PBL connectors with full consideration of each shear contribution is established. The main conclusions drawn from this study are as follows:


To know the expression of Mesenchymal–Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis.we used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis.130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition.Our results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC. In 2018, HER2−) . About 2, HER2−) . TNBC is, HER2−) . Current, HER2−) , 7. PrevMET  is a receptor tyrosine kinase which could be activated by its ligand hepatocyte growth factor (HGF). The activation of MET and its downstream signaling pathway involved in a number of important biological activities, including tumor cells growth, proliferation and metastasis , 9. ReceIn this study, we detect the expression of MET and FASN in TNBC, and analysis the correlation of MET and FASN with clinic pathological characteristics. 130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition. Combined analysis indicated that the TNBC patients with MET and FASN positive expression displayed a worse overall survival. And the AUC was higher than 0.6, which indicated that the combined used of MET and FASN could predict the survival situation more accurately.This study was carried out in accordance with the World Medical Association’s Declaration of Helsinki and approved by the Research Ethics Committee in The Affiliated Tumor Hospital of Xinjiang Medical University. A total of 218 TNBC patients which confirmed by pathological examination in the affiliated tumor hospital of Xinjiang medical university from 2013 to 2015 were collected Table 1.2O. (3) We used hydrogen peroxide solution to block endogenous catalase activity . (4) The primary antibody  was incubated at 4°C overnight. Then washed it with PBS for 5 min and repeated three times. (5) Biotin conjugated secondary antibody was added and incubated at room temperature for 30 min, following with three times wash by PBS for 5 min/time. (6) Add chromogenic reagent for incubation 3 min, hematoxylin dyeing for nuclear staining and dehydration for seal the slide.MET antibody (ZA-0636) was purchased from Beijing Zhong Shan Jin Qiao Biotechnology Company. FASN antibody (FNab-03019) was purchased from Wuhan Enfei Biotechnology Company. The operation of immunohistochemistry was strictly in accordance with the content of quality control. (1) The surgically resected tissue of TNBC patients was treated with 10% formalin fixation and paraffin embedding, and then histological sections were performed (4μm). (2) After routine dewaxing and rehydration, we washed the histopathological sections with PBS (pH =7.4) for three times at 5 min interval. After heat-induced epitope recovery, we washed the histopathological sections with ddHThe expression of MET and FASN protein was observed by two-person use double-blind method. All slides contain multiple tissue sections and set antibody or PBS as positive control and negative control. The results were determined by two-person double-blind observation. The ratio of positive cells and the intensity of cell staining were considered to be the judgment criteria. The score criteria for the ratio of MET positive cells were displayed as follows: negative represented 0, <25% represented 1, 26–50% represented 2, 51–75% represented 3, and >75% represented 4. The score criteria for the dyeing intensity were displayed as follows: negative represented 0, light yellow represented 1, dark yellow represented 2, and brown represented 3. A patient is considered to positive for MET if the sum of those two indexes was greater than 4, and negative if they are not . The scoThe follow-up time of this study was calculated from the postoperative period. The primary survival assessment was disease-free survival (DFS) for five years. DFS time referred to the time from the first day after surgery to local recurrence, regional recurrence, or distant metastasis.We first marked patients with both MET and FASN positive as 2 points, marked patients with MET or FASN positive as 1 point, marked patients with MET and FASN negative as 0 point. After the assignment, we classify the sample as following:①Group 1: 1 and 2 points, Group 2: 0 point. ②Group 1: 2 points, Group 2: 0 and 1 point. After group divided, we carried our univariate Cox hazards regression analysis and time-dependent receiver operating characteristic (ROC) curves analysis.IBM SPSS 22 software was used to carry out univariate and multivariate Cox regression analysis, and chi-square test analysis, Kaplan–Meier analysis. P <0.05 was considered statistically significant.In this present study, we used IHC staining to detect the expression of MET and FASN. We found that 130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. The positive rates were 59.6 and 29.8% Table 2.To know the relationship of MET and FASN with the clinical pathological features, we carried out the correlation analysis and found that the positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, we also found that the positive expression of FASN was significantly correlated with diabetes and body mass index Table 3.2 = 4.726, p = 0.030). For FASN, we also found the ratio of DFS in positive expression group and negative expression group were 70.4 and 84.2% respectively. The positive expression of FASN was significantly correlated with cancer recurrence and metastasis   Table 4.At meanwhile, we carried out univariate Cox regression analysis for MET and FASN. The TNBC patients with negative expression of MET (P = 0.036) and FASN (P = 0.029) displayed a better overall survival. The result of multivariate Cox regression analysis indicated that the expression of MET  and FASN  were still correlated with the overall survival.To know whether MET and FASN could be combined for TNBC diagnostic analysis, we divided the TNBC patients into two groups as following: Group 1: 1 and 2 points, Group 2: 0 point. We carried out univariate Cox regression analysis and found that there was no significantly difference in overall survival between groups 1 and 2. And then, we divided the TNBC patients into two groups as following: Group 1: 2 points, Group 2: 0 and 1 point. We carried out univariate Cox regression analysis and found that group 1 displayed a worse overall survival  was positive for MET in the cancer tissue which were significantly higher than that in adjacent tissues. We also found the positive expression of MET was associated with lymph node metastasis, pathological TNM, and pathological stage in TNBC patients significantly. Our results reinforced the relationship of MET with the development of cancers. In addition, we found that the TNBC patients with positive expression of MET exhibited poorer overall survival. Our results not only enhanced the relationship between MET expression and BC survival rate, but also suggested that MET expression was also closely related to the overall survival of BC subtype TNBC .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.