Positive aspects of sexuality remain understudied among young people globally, and consensus is lacking on how to conceptualise different aspects of healthy adolescent sexuality development in order to guide programmes, research, and policy. We propose a conceptual framework that draws on theories and literature related to positive youth development, empowerment, human rights, gender, social-ecological and life-course perspectives. The framework highlights six key competencies for healthy adolescent sexuality development: (1) sexual literacy, (2) gender-equal attitudes, (3) respect for human rights and understanding consent, (4) critical reflection skills, (5) coping skills, and (6) interpersonal skills. These competencies have the potential to strengthen or impede adolescents’ sense of sexual wellbeing in relation to both themselves  and others . Whether adolescents are able to translate competencies into desired actions and achieve a sense of sexual wellbeing depends on the resources available to them, their agency, and on the influence of social-ecological opportunity structures. The framework can provide concrete direction for sexual and reproductive health practitioners and researchers by providing a platform for recognising and operationalising indicators of healthy sexuality development, and serve as a Theory of Change for programmes aiming to improve adolescent sexual and reproductive health and wellbeing. Our assets-based, life-course approach can also be used to make the case to donors and policymakers for why early investments and positive approaches to adolescent sexuality are needed to achieve sexual wellbeing over time. The framework is based on an extensive narrative review of the literature to identify key components, followed by input from over 20 global experts in the field of adolescent SRHR during workshops, conferences and webinars. We begin with a background on adolescent sexuality development and wellbeing based on existing definitions and conceptualisations. We then move on to explain the different components of the framework and discuss its potential implications for medical and public health professionals. We end with reflection on the next steps in terms of refining and validating the framework.Positive aspects of sexuality remain understudied among young people globally,7 Indeed, Tolman and McClelland7 found that 80% of studies on adolescent sexuality in the first decade of the twenty-first century focused on the prevention of negative outcomes. While the latter is not strange from a public health perspective ,2 an exclusive risk focus is problematic in a number of ways.Historically, most research studies and programmes have viewed adolescent sexuality as a problem behaviour or “sickness best prevented” that is both immoral and socially unaccepted – if outside of marriage – and brings both physical  and psychological consequences .a priori problematic, while in fact they are part of a normative developmental process. From a life-course perspective, sexuality development begins at (or even before) birth, and includes various behavioural, relational and normative transitions throughout the life course – with adolescence being one such key transition.11 During puberty, sexual development is accelerated via growth of genitals and hormonal changes, manifesting both physically and emotionally. With growing moral and cognitive development, adolescents increasingly develop abstract reasoning and problem-solving skills, and reflect on their own personal qualities as well as their place in the world – and how they fit in relation to others. Young people gradually develop their sexual orientation, and start to form romantic and sexual relationships and to experiment with different practices.10 Today, sexual initiation during adolescence (within or outside of marriage) is normative in most cultural settings, and the emergence of new contraceptive methods and abortion has further separated sex from pregnancy and childbearing.3 Second, risk and danger-oriented interventions including abstinence-only programmes have been shown not to be effective in preventing sexual risk; and to clash with adolescent’s needs, realities and human rights to explore their sexuality, and to seek and receive SRHR information and services.12 And finally, because sexual activity is almost always conceptualised in terms of penile-vaginal intercourse, and rarely in terms of relationships, pleasure, feelings and other sexual practices, programmes tend to focus on older, heterosexual youth – thereby overlooking what is needed to promote healthy sexuality development among a diversity of adolescents, including sexual minorities and younger age groups.3First, it assumes that adolescent sexuality and related behaviours are 1–7 Such a perspective does not mean that all young people are (or should be) having sex, or that all intimate relations are healthy. It merely implies that adolescent sexuality involves more than (just) avoiding risks and unwanted consequences.4 For example, for some young people sexual abstinence may be the healthiest potential choice at one point in time, and for some it may involve other ways of exploring sexuality than intercourse per se. As such, empowering young people with different skills  that allow them to navigate information and relationships is an essential part of development for all adolescents, irrespective of whether or not they are sexually active.1A growing chorus of voices from scholars and stakeholders are therefore calling for positive or healthy approaches to adolescent SRHR.rights-based approach, which holds that all adolescents have the right to sexual and reproductive health information, self-determination and civil engagement. Rights-based approaches move beyond disease prevention to emphasise healthy sexuality development, empowerment and individuals’ engagement with their surrounding communities. They do this by focusing on issues that are central to the day-to-day lives of adolescents, such as the navigation of gender norms, identity formation, sexual orientation, relationship power, and broader social and cultural messages.14 Rights-based approaches also involve participatory teaching techniques aiming to engage young people in critical thinking.15 There is growing evidence that a rights-based approach can have positive effects on sexual health. For example, a 2015 review found that the most effective sexuality education programmes are those that integrate content on gender and power.17 In addition, evidence from the US shows that a comprehensive sexuality education using a rights-based curriculum also has the potential to affect psychosocial outcomes such as greater knowledge about sexual health, more positive attitudes towards sexual relationship rights, more self-efficacy to mitigate sexual risks in relationships, and greater communication about sexuality and relationships with parents.13Positive views on adolescent sexuality are closely connected to a 7 Such a perspective is rooted in Developmental Systems Theory and Positive Youth Development (PYD), which suggests young people should be seen and nurtured as resources rather than being problematised.19 The premise of PYD is that in order to promote and sustain healthy outcomes in adolescence, programmes should focus on strengthening five central domains of developmental assets, sometimes called the “five Cs” of PYD – Competence , Confidence (e.g. sense of positive self-worth), Character , Connection (e.g. positive bonds with others) and Caring (e.g. sense of sympathy and empathy). These domains are interactive, meaning that adolescents “thrive” when they experience healthy development within each of the five Cs.19 Evidence shows that building on adolescents’ developmental assets in line with PYD can have both immediate and long-term positive effects on their health and wellbeing.20 For example, Blum et al.10 propose four central outcomes of healthy development during early adolescence, including: life and decision-making skills, self-efficacy, emotional and physical safety, and engagement in learning; each of which have been linked with sexual and reproductive health  later in adolescence, and are thus closely connected to healthy sexuality development. Further, a 2016 review found that positive aspects of sexuality are linked not only with sexual health, but with physical and mental health as well overall wellbeing.21Adolescent sexuality development does not occur in isolation, but interacts with other developmental facets , and is shaped by the complex interplay between individuals and their social-ecological environment.2 “a fine line may divide exploratory sexual activity that ultimately contributes to positive sexual identity and competence, and sexual activity that significantly increases risk of harm”. From a PYD perspective, the role of SRHR interventions is to help young people navigate that “fine line” which may divide potentially positive sexual experiences from those that are harmful.2 In order to do so, programmes and research need to include meaningful efforts to understand and strengthen young people’s developmental assets, ultimately affecting their  wellbeing.As noted by Halpern,9 including during the earliest years (ages 10–14) which is a critical period for shaping attitudes and behaviours,10 in order to inform research and practice. Below we take a closer look at existing definitions and frameworks that have attempted to conceptualise healthy sexuality and related constructs.Nonetheless, consensus is lacking around how to define and measure broader, affirmative aspects of adolescent sexuality development,sexuality is a “ … central aspect of being human” that “is experienced and expressed in thoughts, fantasies, desires, beliefs, attitudes, values, behaviours, practices, roles and relationships”. The WHO further defines sexual health as a “state of physical, emotional, mental and social wellbeing in relation to sexuality”, including the possibility of experiencing “pleasurable and safe sexual experiences”, and emphasising individuals’ sexual rights, such as that to equality and non-discrimination, privacy, information and education about sexuality, freedom of opinion and expression, to choose if and with whom to be sexually active, and to make decisions related to marriage, pregnancy and childbirth.22Applying a positive lens towards sexuality is in line with several international definitions. For example, the World Health Organization (WHO) emphasises that sexual and reproductive health and rights (SRHR). This definition draws on already-existing international agreements and documents, emphasising how sexual health is intrinsically linked with sexual rights, reproductive health and reproductive rights. It explicitly mentions that a “positive approach to sexuality and reproduction should recognize the part played by pleasurable sexual relationships, trust and communication in the promotion of self-esteem and overall wellbeing”.23 Similarly, over two decades ago the US National Commission on Adolescent Health defined sexual health as the “ability to develop and maintain meaningful interpersonal relationships; appreciate one’s own body; interact with both genders in respectful ways; and express affection, love and intimacy in ways consistent with one’s own values”.24Such a positive, rights-based view on sexuality is further underscored in the 2018 Guttmacher-Lancet Commission integrated definition of 25 further define sexual wellbeing as distinct from (rather than adjunctive to) sexual health. They do so by placing sexual wellbeing and sexual health alongside sexual pleasure and sexual justice as four intersecting pillars that underlie public health studies and programmes. Sexual wellbeing is conceptualised as spanning seven domains: “sexual safety and security, sexual respect, sexual self-esteem, resilience in relation to past sexual experience, forgiveness of past sexual events, self-determination in one’s sex life, and comfort with one’s sexuality”25 – all of which applies to people regardless of whether they are sexually active or in relationships. The authors points to the need to monitor sexual wellbeing outcomes as important public health indicators in their own right, e.g. as markers of health equity, so as to recognise the role of context, transgenerational trauma, and needs of marginalised populations.In their recent (2021) framework for sexual wellbeing in mid and later life, Mitchell and colleaguesIn addition, a few scholars have focused specifically on conceptualising adolescent sexuality from an affirmative perspective, using overlapping terminologies such as “healthy”, “normative” or “positive” as well as “sexuality”, “sexuality development”, “sexual wellbeing” or “sexual health”.26 conceptualise adolescent sexual health as spanning four domains: “physical” , “mental” (e.g. condom efficacy), “social”  and “emotional” . Using data from a longitudinal cohort of US adolescent girls, the authors found that girls’ sexual health can be measured as a multi-dimensional construct spanning these domains, which in turn is linked with different sexual prevention behaviours such as condom use and sexual abstinence – making sexual health an “important construct for promoting positive sexual development” regardless of adolescents’ experiences.26Hensel and Fortenberry3 define adolescent sexual wellbeing as spanning four key dimensions: “sexual self-esteem” ; “sexual self-efficacy” ; to have “feelings of arousal, satisfaction, and pleasure as well as recognizing that one is entitled to these feelings”; and “freedom from pain, anxiety, and negative effects regarding sexuality” – irrespective of whether or not a young person has engaged in any sexual behaviours. Not engaging in sex (abstinence) could thus reflect a high sense of wellbeing in the form of an active choice, or low levels of wellbeing . Harden argues that these dimensions of sexual wellbeing can be thought of as a type of “sexual subjectivity”, defined by Shalet27 as:“the capacity to be aware of one’s sexual feelings, to enjoy sexual desire and pleasure, to conceive of oneself as the subject [rather than the object] of one’s sexual activities, and to experience a certain amount of control in sexual relationships.”3Harden21 defines positive aspects of sexuality as including sexual self-efficacy, sexual self-esteem, sexual pleasure and sexual satisfaction, pointing to sexual satisfaction as an overarching concept encompassing both pleasure and self-esteem. She conceptualises sexual self-efficacy as overlapping with the concept of sexual subjectivity, or the “capability to act as a subject in one’s sexual life”, for example by asserting preferences and boundaries, whereas sexual self-esteem refers to the “confidence and comfort that one feels with their own sexuality” including to communicate with others.Similarly, Anderson28 further describe healthy adolescent sexual development as having a basic understanding (e.g. of the body) as well as positive attitudes and skills to support sexuality development. They emphasise agency (being in control of one’s own body and decisions) and resilience (learning from bad experiences) as key dimensions, and that a life-course perspective is central where children are “naturally curious about their bodies and sexualities”.28 While the authors highlight the complex, multidimensional nature of sexuality development, the description of each of the 15 domains is not very detailed, and it is not clear exactly how they interact and relate to each other.McKee and colleaguespositive adolescent sexuality development is proposed by Arbeit,1 focused specifically on skills that allow young people to engage positively with their own sexuality, interact with others, and contribute meaningfully to society focus, including: “sexual selfhood”, “sexual negotiation with others”, and “sexual empowerment”, which in turn are linked via personal intimacy, agency and social advocacy. Specifically, Arbeit argues that an individual’s sexual selfhood may shape their personal agency, which in turn determines their ability to negotiate with others (e.g. by obtaining or giving consent). Negotiations in relationships may in turn affect intimacy, which can lead to sexual empowerment of a young person to advocate for personal needs, thereby affecting their sexual selfhood. How and when adolescents develop these skills vary and is shaped by multiple interacting biological, cultural and social influences such as gender, race, class and contexts.1A more elaborated framework for 1 or that more explicitly operationalise sexual wellbeing outcomes (such as Mitchell and colleagues),25 they seem to be (more) applicable to (older) age groups who are already in relationships and/or sexually active, and less so to the earliest years of adolescence. Comprehensive sexuality education, for example, aims not only to prevent traditional public health outcomes but to improve “soft outcomes” such as gender equal norms, consent communication and perceived self-efficacy in relation to different age groups (from early childhood to late adolescence).29 Design and evaluations of such programmes would thus benefit from a framework that more concretely operationalises healthy sexuality development over the course of adolescence and places this in relation to wellbeing outcomes. We also note that all frameworks were primarily developed by Western researchers; and that research on healthy adolescent sexuality in other parts of the world, including low- and middle-income countries, is largely missing.Based on our review of the above definitions and frameworks, we note that most existing models tend to be academic/theoretical rather than application oriented in their nature, thereby limiting the application to programme development and evaluation. And even for those that are more focused on skills (such as Arbeit’s model)themselves and others. Indeed, a recent review found that operational definitions of sexual wellbeing span individual, interpersonal and sociocultural dimensions, and highlighted the need to apply a capability lens that focuses on what young people are “able to be and do” rather than what they “have and do”.9 In essence, this means that healthy sexuality development and wellbeing is intrinsically linked with sexual empowerment, where agency and competencies or resources play a key role in determining adolescents’ ability to navigate their surrounding contexts.Nonetheless, what becomes clear across the frameworks and definitions is that they all emphasise healthy sexuality development as encompassing knowledge, skills and attitudes, which in turn affect individuals’ sense of sexual wellbeing in relation to 31 A key component of empowerment is agency, which refers to the ability to make/influence decisions and assert own interests and opinions.32 Agency is closely connected to the resources available to a person – including both those proximate  as well as surrounding opportunity structures at a more distal level such as norms, laws and policies, physical, cultural and economic environment.32Sexual empowerment can be thought of as the processes of expanding young people’s choice and strengthening their voice related to sexuality through the transformation of power relations, whereby they are able to assert their opinions and desires, influence and make purposeful decisions, and challenge existing norms and structures with respect for consent and the rights of others.33 Similar to a PYD approach, this framework conceptualises “life skills” as the combination of knowledge  and skills (“what one has”) into a “broader set of competencies” that allow young people to “function, thrive and adapt in their lived realities”.33 By focusing on knowledge, attitudes and skills as different but interlinked competencies, the authors aim to broaden the narrow focus on skills (e.g. self-efficacy) and bring attention to how such resources can be used for transformative change. This is where agency and opportunity structures come into play. Whether or not a young person is able to translate competencies into empowered action (towards desires outcomes) depends on their own agency and the agency of others, as well as the degree to which their social context enables change (via opportunity structures).A useful approach to thinking about the role of resources and its interaction with agency is the conceptual framework for gender transformative life skills programming developed by Kwauk and Braga.healthy sexuality development as the process through which young people build competencies in the form of knowledge, skills and attitudes that support sexual wellbeing in relation to themselves and others. Specifically, we propose six interrelated domains of key competencies that are central to healthy adolescent sexuality development, whether or not sexual activities occur. We view healthy sexuality development as being closely linked with sexual empowerment, and not limited to the “normal” biological developmental phases of adolescence. Whether young people are able to translate competencies into desired actions and achieve a sense of sexual wellbeing across the life-course in turn depends on the personal, social, medical and economic resources available to them, on their  agency, and on the influence of social-ecological opportunity structures. Strengthening healthy sexuality development thus involves empowering young people to feel comfortable with the normative physical, emotional, cognitive and social  changes that they are going through, to navigate their surrounding contexts and to form mutually respectful relationships and interactions. For example, it is not only about having (normative) feelings of desire, attraction and arousal, but being able to navigate and understand these feelings.Drawing on the literature, we differentiate between Below we explain the framework components in more detail.multiple, interlinked social-ecological factors shape adolescents’  development and wellbeing, including – but not limited to – opportunity structures at individual ; family ; peers ; school ; neighbourhood , health systems  and wider societal levels .10First, life-course perspective11 is implicit in the framework given that the process of sexuality development is something that occurs from (or even before) birth,7 with adolescence being a key transition point of developmental changes.11Second, a human rights-based, gender-transformative approach to recognise adolescents’ fundamental right to sexual and reproductive health information, services, participation and non-discrimination.23 It recognises gender equality, and particularly equitable gender norms, as central to adolescent development and wellbeing – in line with global evidence that gender transformative programmes can successfully impact health-related knowledge, attitudes and behaviours,34 and that healthy adolescent development thus includes the ability to identify and critically examine rigid gender norms.16Third, it draws on a n empowerment-based approach30–32 and capability lens9 to highlight how adolescents’ assets (in the form of competencies) interact with agency and opportunity structures to affect sexual wellbeing. In essence, is about building and nurturing assets in line with the “five C’s” of PYD, including confidence, character and caring.19Fourth, it uses areciprocal and complex nature of sexuality development,35 shown in how the framework components are not linear, but dynamic and interactive, and by pointing to the interconnection between different competencies. Similarly, past experiences inform new ones: for example, if young people are subject to bullying, this will likely affect their attitudes and how they go about forming relationships in the future. For this reason, it is important not to view the different framework components as a checklist that one has to achieve, i.e. failure to achieve certain outcomes does not mean that one is “unhealthy”.Finally, it emphasises the The framework is guided by five key principles:knowledge, skills and attitudes: (1) sexual literacy, (2) gender equitable attitudes, (3) respect for human rights and understanding of consent, (4) critical reflection skills, (5) coping skills and stress management, and (6) interpersonal relationship skills. These competencies have been introduced briefly elsewhere,36 and can be thought of as internal resources to support healthy sexuality development irrespective of whether a young person has engaged in any sexual activities. These competencies move beyond mere knowledge about sexual and reproductive health to span aspects such as coping and communication skills, critical consciousness, and developing personal values that support gender equality and human rights. Many of these competencies are similar to those described in Arbeit’s1 skills-based model for adolescent sexuality development and can act as boosters as well as barriers for sexual wellbeing from a personal as well as relational perspective.37 They are also very much in line with the knowledge, attitudinal and skills-based learning objectives laid out in the International Technical Guidelines for Comprehensive Sexuality Education.29Drawing on empowerment theory, the framework highlights six key domains of competencies for healthy sexuality development in the form of Sexual literacy refers to a developmentally and age-appropriate basic knowledge and access to information related to the human body, development, sexuality and SRHR.29 According to the International Technical Guidance for Sexuality Education, the specific content and meaning of basic understanding will vary according to age and developmental stage; for example, in early adolescence this might include an understanding of the human body and development including puberty, emerging feelings and emotions, the meaning of different relationships , and an understanding of gender. Whereas in later adolescence it might expand to knowledge around sexual behaviour, sexual and reproductive health, and where to seek services and support.29 The specific SRHR needs and concerns of adolescents vary within and across regions, countries and communities, and this will affect what is considered both appropriate and relevant information.29Gender equitable attitudes points to the importance of holding views that support gender equality. As young people transition into adolescence, they are increasingly exposed to social and cultural expectations and messages about the roles, responsibilities, values, power and relationships of men and women, boys and girls. While such gendered norms vary across times and cultures, a set of stereotypical norms prevail in most settings that associate sexual prowess with being a “man” while the same is stigmatised for girls and women.41 Evidence shows that agreement with such stereotypical norms has consequences for adolescent SRHR, such as masculinity norms pressuring young men to use violence and take sexual risks,40 and that perceived gender norms in early adolescence are linked with a host of outcomes related to sexuality and wellbeing such as pornography use,42 body satisfaction,43 and mental health.44 Developing attitudes that support gender-equal norms are thus an important part of healthy sexuality development.Respect for human rights and understanding of consent highlights the fundamental connection between sexuality and health with human rights,45 focusing on the ability to demonstrate respect, tolerance and empathy for others irrespective of their characteristics.14 Such skills can involve the application of personal values and moral reasoning to distinguish between right and wrong with regard to how to treat ourselves and the people around us. Similarly, as described earlier, applying a rights-based approach to sexuality education has been found to boost positive attitudes towards sexual relationship rights, sexual self-efficacy and communication about sexuality and relationships.13 Demonstrating respect for human rights is thus closely connected with ethics, and furthermore about understanding the nature and complexity of consent (e.g. what does it mean to say or give consent?).46 Evidence indicates that young people are able to define sexual consent and that both boys and girls consider it to be important, but that communicating and interpreting consent signals in real-life situations can be more ambiguous .56 In the context of our model, respect for human rights might – for example - include positive attitudes towards sexual and reproductive rights, such as the rights of sexual minority groups and to freedom from gender-based violence.Critical reflection skills can be thought of as the ability to recognise and understand how social norms and structures shape one’s own feelings, behaviours and experiences.1 It is not just the cognitive process of reflection, but an understanding of the personal and social world which is shaped via interactions and relationships. Adolescents in most cultural settings are growing up in a context characterised by multiple, and often conflicting, messages and norms related to sexuality and gender – most of them informed by a heteronormative narrative. As a result, adolescents need skills to process different ideas related to what is socially or culturally “ok” (or not) to feel or do , for whom (e.g. only between men and women), and under what circumstances (e.g. only within marriage).49 Critical reflection skills are thus essential to allow adolescents to take a step back, reflect and distance themselves from dominant social-sexual norms in way that is in line with their own values.51 As noted by Bay-Cheng,51 such critical reflection is essential to be able to “plan actions with which to build a world that may better promote their sexuality development and better support sexual thriving”. This involves both the ability to reflect on messages related to one’s own peer group but also to take the perspective of other social groups, e.g. of different gender, ethnicity, social class, sexual orientation.Coping and stress management skills refers to the ability to recognise, manage and adapt to different types of internal or external stressors related to sexuality and development.53 Normative adolescent sexuality development involves multiple and often difficult changes,7 which – whether or not they are positive or negative – can feel overwhelming and stressful.1 Coping is a dynamic process to both manage and adapt to different types of stressful internal or external changes, i.e. it involves skills not only to recognise emotions, but to identity and manage stressors and locate relevant individual or social support.53 Coping skills can help adolescents to learn from and translate negative experiences into new ideas and boundaries, as well as seek support in line with their needs,35 for example from adults who are close to them, whether a teacher, parent or other professional. Such skills can involve being able to interpret and deal with other people's reactions to one's  preferences and desires , and to resist and “deconstruct” dominant social and cultural messages related to gender, sexuality and power.1Interpersonal relationship skills include the ability to communicate and negotiate with others, not only in relation to intimate partners, but with peers, family members and others that influence adolescents’ lives. Such skills can include the capacity both to seek information and assert one’s own preferences, as well as being able to listen to and respect others.1 Doing so involves the skill to ask for and give consent, as well as refusing and being able to accept refusal of consent.46 Interpersonal relationship skills may thus help both to prevent unwanted interactions and sexual assault, and to promote positive, pleasurable intimate relationships.9 Indeed, a recent review of adolescent sexual wellbeing indicates that young people want skills to talk about SRHR; that sexual communication with partners is associated with (greater) sexual pleasure feelings of safety and support; and that talking with friends and family members about sexuality and relationships has been linked with greater sexual assertiveness and other aspects of sexual wellbeing.56personal and relational aspects of sexual wellbeing and give examples of potential outcomes. Our conceptualisation is in line with the sexual wellbeing domains proposed recently by Mitchell and colleagues,25 e.g. comfort with sexuality, sexual self-esteem, and safety and security – albeit with different terminology and adapted specifically for the adolescent population.The framework further shows how each of the interconnected healthy sexuality competencies can contribute to adolescent's sense of sexual wellbeing (or lack thereof). Here, we differentiate between By personal sexual wellbeing, we mean aspects such as having a positive sense of one’s own  self  and body .9 Having a positive sense of self and body is closely linked to the concept of “sexual selfhood” and can include the capacity to be aware of one’s sexual desires,28 recognising that it is fine to enjoy these feelings and to experience pleasure,28 sexual self-esteem (sense of self-worth and attractiveness) and self-efficacy (perceived ability to assert preferences).3 Two central outcomes are self-esteem and self-efficacy related to interpersonal relationships. Self-esteem can be thought of as an individual’s sense of self-worth and attractiveness as well as competence in romantic and sexual situations, whereas self-efficacy refers to the “perceived ability to assert preferences and desires” with a partner, including the desire not to engage in any romantic or sexual activities, and to negotiate condoms and contraceptives to protect against HIV/STIs and unintended pregnancy.3 These constructs interact with feelings and experiences related to the development of the physical body including body image and appreciation, level of comfort in relation to body changes that occur in puberty including menstruation.58relational sexual wellbeing, we refer to a sense of  safety and security via mutually respectful relationships that are characterised by gender equality and free from violence and coercion. For adolescents and especially the youngest age groups, having mutually respectful relationships does not only include those with intimate partners, but – and perhaps more importantly – also those with other people who are relevant to their social contexts and who are part of their sexual socialisation, such as parents, peers, relatives and community members.7 In the context of this conceptual model, outcomes measuring wellbeing in relation to peers might look at experiences of bullying, teasing, harassment and violence related to gender and sexuality, as well as perpetration of psychosocial and physical types of violence against other peers.37 Over time, relational sexual wellbeing can extend into that related to intimate relationships, such as perceived power and communication, self-determination and respect in relation to sexual partners, and resilience related to (past) sexual experiences. 28 As adolescents age and engage in sexual relationships, the links between sexual wellbeing and sexual health  and sexual pleasure also become more apparent and relevant from a public health perspective. 25By  Whether or not individuals are able to translate competencies into action depends on their agency or ability to negotiate which intimate and/or solo sexual activities, if any, to engage in. In the context of this framework, sexual agency forms the link between competencies and wellbeing, and can be thought of as adolescents’ ability to realise preferences and choices, express voice and influence and make decisions by drawing on resources at multiple levels.30 We view agency as being relational, with young people’s personal agency being closely shaped by, and shaping, the agency of others in their social contexts.35 As described in Arbeit’s skills-based model, sexual agency forms the connection between skills related to self  and others (negotiation with intimate partners): thus, personal agency is strongly shaped by, and shapes, the agency of intimate partners. It is also linked with the agency of other people in their social networks  as well as the broader societal structures and institutions that surround them.35 Likewise, sexual agency is not something that is equally available to all people – multiple institutional structures restrict individuals’ ability to be their own, autonomous agents, such as laws and policies, social and cultural norms, heteronormativity and inequalities related to race, ethnicity, sex and gender identity.51We further recognise that sexual agency is not always positive from the views of an external observer, but that it includes the ability to “endure, suffer and persist”.Navigation refers to how young people make decisions about their sexuality in light of multiple goals, circumstances, past experiences, feelings, expectations, sense of benefits and risks, where clear-cut right or wrong answers or decisions are not always apparent or available. While a focus on individuals’ freedom to choose is important from a rights-based perspective, it entails that young people are always in control and responsible, which may not be the case. In other words: making healthy choices and exercising agency related to sexuality can entail making the “wrong” choices, if these are the best available options for the individual at a certain timepoint.35 For example in a context of poverty and where transactional sex is the norm, adolescents may choose to have unsafe sex because the benefits  outweigh the risks (of getting pregnant or HIV/STIs) in light of other goals than health, e.g. to bring food back to the family, to get money to start a business, or to strengthen the relationship.30–33 While knowledge, skills and attitudes are important, these can be limited or annihilated by an individual’s family, peers, community and broader societal context,10 such as having a violent partner, lack of support structures, lack of access to contraception, etc. Opportunity structures exist at multiple, interacting levels including the individual , family , peers (e.g. networks and norms), community  and the broader societal level .10 For example, imagine an adolescent girl who is in love with one of her female peers. Whether or not she is able to translate her knowledge (e.g. about different types of romantic attractions), attitudes (that same-sex relationships are fine) and skills (e.g. to form relationships) to act on her feelings depends on her context, such as: whether homosexuality is legal in her country, whether social norms stigmatise rather than accept same-sex relationships, whether her family would be supportive, or whether she knows peers with similar experiences. These opportunity structures thus play a critical role in determining her agency and sense of sexual wellbeing.Finally, the framework highlights the role of the social-ecological opportunity structures in determining if, how and when adolescents are able to translate competencies into desired actions.positive and responsible way with their sexuality” and highlighted young people’s right to comprehensive sexuality education.59 Despite this vision, programmes and research remain largely shaped by a traditional risk approach to adolescent sexuality.60 This includes evaluations of comprehensive sexuality education programmes which tend to focus on measuring outcomes related to two main public health indicators (teenage pregnancy and STIs), despite the increased call for measuring “soft outcomes”  as important in their own right.61 While the past 25 years have seen significant progress in adolescent SRHR, data and evidence on sexual wellbeing outcomes remain scant – especially in low- and middle-income countries.60The importance of investing in adolescent SRHR from a broad perspective was first recognised at the 1994 International Conference on Population and Development (ICPD), which called for “meeting the educational and service needs of adolescents to enable them to deal in a 62In response to the continued push towards positive approaches, this review makes a first attempt at proposing a conceptual framework that can be used to inform both programmes, research and practice. First, the framework can provide concrete direction for designing and evaluating adolescent SRHR initiatives that are rights-based and gender transformative. It can help to articulate a Theory of Change for how CSE programmes, for example, can contribute to sexual wellbeing by strengthening adolescents’ skills to reflect upon and navigate different scenarios, regardless of whether few options are available to them. It shows that merely giving information is not enough, but that adolescents need skills to critically reflect on messages, including those communicated via pornography and media.www.geastudy.org), for example, uses a number of indicators to measure young adolescents’ personal sense of sexual wellbeing , as illustrated in a recent study where we analysed data from the Indonesian arm of the GEAS.63Second, the framework can be used to guide the operationalisation of measures that tap into the complex construct of sexual wellbeing from both personal and relational aspects. The Global Early Adolescent Study .Third, our assets-based, life-course approach can further be used to make the case to donors and policy makers for why early investments are needed to achieve wellbeing over time. There is growing attention on considering the value of non-health outcomes in cost evaluations25 More research is needed to understand sexual wellbeing and what this entails from the perspective of young people themselves according to their social contexts, beyond high-income Western countries where most existing frameworks and data come from today. In light of this, an important next step will be to validate and further refine the framework by engaging with young people, the public and other key stakeholders in different settings globally. Our involvement in the GEAS and partner initiatives such as the Explore4Action programme provides an excellent opportunity to do so, both in relation to empirically testing the framework in relation to a broad range of measures, as well as seeking input from cross-cultural networks of professionals and young people involved in the research and programmes implemented.When using the framework, researchers, donors and programme implementers need to consider carefully the broader experiences and context of adolescents’ lives. Young people’s ability to utilise knowledge, skills and attitudes gained via any intervention depends on the resources available to them, their  agency, and on the influence of opportunity structures. This means that the specific content and framing of many of the domains in the framework will vary depending on the geographical, social, economic and cultural setting where it is being applied, using intersectional approaches and carefully adapting content related to – for example – histories of trauma and marginalisation.4 We hope that the model can serve as a roadmap to realise the ICPD vision of allowing young people to navigate their sexuality in a “positive and responsible” way.59Nonetheless, the framework’s grounding in literature on adolescent development as well as internationally agreed definitions of sexuality suggests that it is both relevant and possible to use across different contexts. In some settings it might serve as a starting point for implementers, researchers and policy makers to set priorities and make the case for viewing adolescent sexuality from a positive perspective. In others, it can help to reaffirm and operationalise what medical and public health professionals across the globe have known for decades: that adolescents’ health and wellbeing, including their sexual wellbeing, is more than just the absence of disease.


The hypothesis was tested with SEM analysis, setting the child’s internalized/externalized problems as dependent variable, maternal depression as independent variable, and stress as a partial mediator. (3) Results: Both depression during pregnancy and recent depression has not only a direct effect on the internalizing and externalizing symptomatology of the child, but also an indirect effect through parental stress. Significant direct and indirect relationships were found. (4) Conclusions: Maternal depression and the presence of parental stress can influence children’s behavioral problems, both internalizing and externalizing. Given the high prevalence of depression in woman, and the fact that this disease also affects three times more women who are raising children , we can In Chile, there is evidence of high prevalence of female’s depression  as well The association between stress and depression has been previously studied ,6. CurreThe relevance of the topic is twofold. It has first a theoretical relevance, which is to identify how parental stress and maternal depressive symptomatology affect socioemotional development and behavioral problems in early childhood. Secondly, it has a practical relevance, which is to validate the importance of caregivers’ wellbeing. Finally, it is also important to generate more local research information, which will help policymakers to design preventive interventions.From this perspective, we seek to answer the following research question: How do mothers’ depressive symptomatology and parental stress influence children’s socioemotional development and behavioral problems in early childhood?We use the term depressive symptomatology to refer to the behavioral manifestations that configure a mood disorder characterized by a depressed state that manifests itself through a loss of pleasure or interest, changes in appetite or weight, sleepiness, low energy, guilt, difficulties in thinking, concentrating, or making decisions, and thoughts about death, among other features appearing during the last two weeks .There is evidence of the effects of depressive symptomatology on children’s upbringing and interactions with their parents, which includes social models, attachment, monitoring, and discipline .There is also evidence that mothers’ depression is related to changes in family functioning through inadequate role models . Mother’According to the attachment theory, when a mother is depressed, the relationship with her child is affected through low sensitivity and availability. Similarly, according to neurobiological theories, in periods of critical growth—such as the first years of life—during which important social, affective, and cognitive information is acquired, maternal failure to provide stimulation will have certain repercussions on the socioemotional area . From thA study of 290 mothers seeking professional advice at primary care centers in Chile estimated that 51.9% of the children of depressed mothers had psychiatric symptoms . Among tFinally, research shows that certain characteristics of children, such as health problems or irritability, could affect a mother’s depression. In other words, a mother’s concerns about a difficult or sick infant may affect her state of mind and worsen both her symptomatology and her child’s difficulties . ChildreThe definition of parental stress includes parents’ negative feelings regarding their own parenting skills and also negative feelings towards their offspring , causingChildren of families that cope with continuous distress during children’s first three years of life could be more exposed to develop emotional and behavioral difficulties, but also develop parent-child relationship difficulties . SpecifiAdditionally, there is a relationship between children’s development and parental stress. This evidence is significant for socioemotional development if we consider that “problems detected in school have a marked emotional aspect and only by combining the Intellectual Quotient with the Emotional Quotient can good results be achieved” ,27. MoreOn the other hand, it has been proposed that boys tend to display more externalizing problems than girls ,30,31, wSocioeconomic status (SES) is related to the quality of the family environment, which is poorer in lower-stratum families. Khawaja, Barazi, and Linos  show thaAccording to Rodriguez and Muñoz  who analAs for mental health, The National Health Survey ENS 2009–2011 shows a higher prevalence of depressive symptomatology in women and in people with a lower educational level .Additionally, Ulloa, Cova, and Bustos  analyzedParticipants were 6335 mother/child pairs drawn from the ELPI. The data used are a subsample taken from the first two rounds of the ELPI (2010 and 2012) . The firn = 15,754) of the homes surveyed in the first round (2010) and 98.2% of those surveyed in the second round (2012). Then, we linked the first and second round databases, which yielded a sample of 12,611 cases measured at two points (2010 and 2012). Given that the main aim of this study was to understand how parental depression and stress can influence the child’s internalized and externalized symptomatology, we selected homes where child symptomatology was measured with the Child Behavior Check List 1 (CBCL1). This was achieved by selecting those children who were within the age range of the instrument (18 to 72 months) at each of the two points when it was administered. A total of 7181 cases were identified. Finally, 822 cases, corresponding to mothers who decided not to answer the parental stress instrument, were discarded, and 24 cases were left out because these mothers reported having received no formal education whatsoever.For this paper, we selected homes where the biological mother lives with the child, which represent 98.8% , while their children are between 39 and 72 months old . Like most other surveys in developing countries, the ELPI provides very detailed information on household assets; thus, it is necessary to reduce the dimensionality of the SES information provided to create a SES score which captures the underlying socioeconomic status of the household. To do this, we used a polychoric principal component analysis, following the approach laid out in Kolenikov and Gustavo . This alMaternal depression. Maternal depression was determined through these three questions: “Were you diagnosed with depression during pregnancy”, with 11.5% (n = 730) of affirmative answers; “after pregnancy, were you diagnosed with postpartum depression by a specialist?”, with 12.5% (n = 780) of affirmative answers; and “have you recently been diagnosed with depression by a specialist?”, with 12.0% (n = 758) of affirmative answers. The last question was made only in the year 2012. Using these data, we created three variables: depression during pregnancy, postpartum depression, and current level of depression.Child Externalizing and Internalizing Behavior. Child behavior was measured by The Child Behavior Checklist 1 (CBCL/1 1⁄2–5). This instrument is administered to the child’s caregivers, who were asked to rate the degree to which they believe each item on the CBCL is true about their child’s behavior within the past 2 months on a scale from 0 (not true) to 2 (often true). The CBCL includes two broadband scales, including in total 99 items. The first, labelled “Internalizing” problems (36 items) consists of four syndrome subscales . Examples of these items are: “Clings to adults or too dependent”, “Diarrhea or loose bowels (when not sick)”. The second scale, “Externalizing” problems (24 items), consists of two syndrome subscales (Attention Problems and Aggressive Behavior). Examples of these items are: “Can’t concentrate, can’t pay attention for long”, “Hits others”. Standardized T scores are used to estimate a child’s level of impairment relative to the population and cut points have been prescribed for children with scores falling into the “borderline” (93rd percentile) and “clinical” (98th percentile) ranges.The CBCL/1.5–5 Inventory is an internationally recognized instruments for evaluating maladaptive behaviors that may affect the present and future development of preschool children between 1.5 and 5 years of age  [(PSI-SF) . This in(PSI-SF) . With reThis study uses the PD scale because it has been shown that higher parenting stress is related to caregivers’ depressive emotion . AdditioTo evaluate the presented model, a structural equations model was used, using the lavaan statistical package . The weiThe model uses two measurements of internalized and externalized problems, one of which was done in 2010 and the other in 2012. The purpose of incorporating two measurements is to control for the baseline state of internalized and externalized problems of the child, so that to determine if the other variables of relevance to the study, specifically parental stress and the various forms of depression, are capable of influencing the child’s symptoms once it has been controlled for what appears to be more stable in the child’s development, and therefore less dependent on context. On the other hand, the sociodemographic variables already presented as control variables were used.2 (5870) = 51811.053, p < 0.001, CFI = 0.930, TLI = 0.946, RMSEA = 0.038, SRMR = 0.057. Regarding the hypothesized associations, it is observed that the presence of depression in pregnancy, the presence of a recent depression diagnosis, and the scores of internalized and externalized symptoms measured 2 years earlier, are positively associated with parental stress once sociodemographic variables were controlled for. It is also possible to observe a stability in the scores of externalized problems since the previous score of externalized problems is strongly related to the later externalized problems. Furthermore, it is observed that parental stress, the presence of a diagnosis of depression during pregnancy, and the diagnosis of recent depression are associated with the externalized problems of the child.The explanatory model of externalized problems see  had a goRegarding the mediation hypothesis, it was observed that internalized and externalized problems, as well as depression in pregnancy and recent depression, are associated with externalized problems through parental stress as shown in 2 (7256) = 63739.96, p < 0.001, CFI = 0.895, TLI = 0.916, RMSEA = 0.038, SRMR = 0.060. Since this model shares the same predictors on parental stress from the externalized problems model, the beta coefficients are practically the same  and the difference in R2 is only 0.002, , so the The explanatory model of internalized problems see  had a goRegarding the hypothesized associations, it is observed in Regarding the mediation hypothesis, it was observed that internalized and externalized problems, as well as depression in pregnancy and recent depression, are associated with internalized problems through parental stress as shown in This paper aims to shed light on how maternal depression and the presence of parental stress can influence children’s behavioral problems, both internalizing and externalizing.It was observed that the presence/absence of maternal depression during pregnancy has not only a direct effect on the internalizing and externalizing symptomatology of the child, but also an indirect effect through parental stress. Numerous studies associate depression with difficulties in parenthood, since it generates a distance in the bond of early attachment .Additionally, parental stress and depression during pregnancy is associated with more externalizing and internalizing problems, even when controlling for sociodemographic variables and measurements of behavioral problems made two years earlier. Children of mothers who report having had depression during pregnancy are more likely to display externalizing problems than children of mothers who did not have depression during pregnancy. Furthermore, recent depression is associated with externalizing and internalizing problems. This highlights the relevance of maternal mental health in children’s emotional development.However, depression diagnosed during pregnancy was found to directly affect children’s behavior. This is not surprising, given that numerous studies show an association between depression in the last trimester of pregnancy and regulation problems in children . PregnanRegarding parenthood differences by child gender, it has been shown that mothers are more sensitive to their daughters than to their sons , probablIt is also worth noting that the mother’s SES and educational level were found to have an influence on the child’s internalizing and externalizing problems. This finding can be taken to suggest that these are distal variables whose influence can depend on proximate variables such as upbringing patterns. This is relevant, because it makes it possible to presume that—despite the difficulties and costs of modifying the material and cultural conditions of families—it is possible to adopt strategies aimed at the agents who directly participate in children’s upbringing, at least at the intervention and public policy levels.However, it is important to point out the limitations of this study. First, all the instruments used by ELPI are self-report which could bias the results, especially regarding the reporting of behavioral problems in children when mothers are diagnosed with depression. This is because depressed mothers could perceive their children as being more problematic. Linked to this, it is important to have in mind how hard it may be for a depressive mother to assess her child’s behavior correctly, because this could also affect her perception of the child and in the future. Second, it would be interesting to see in future studies if the behavioral effects on the child are long-term and if they have an impact on their development, by evaluating the child and not just the mother itself. Then, future studies should try to use observational or multi-informants to evaluate child behavior more objectively. Additionally, it would be interesting to analyze in further studies the link between the SES indicator and lower levels of parental stress in women, as it is seen in more traditional cultures/environments that work for women is considered as a limitation to the time dedicated to a child; hence, there could be families with low incomes where women do not work because of that more traditional idea.Finally, it is important to highlight that the results of this research article are useful to encourage new public policies that address the relation between caretakers’ mental health and children’s socioemotional development.Maternal mental health affects children’s socioemotional development and is related to internalizing and externalizing problems in early infancy.It is fundamental to address maternal mental health in public health service during child medical assistance and in educational system.


This article was initially published with an incomplete table provided by the authors, and an erratum published in anticipation of the corrected version. The authors have not responded to multiple requests, and as a result, the article has been fully retracted.The article, “Tranexamic acid reduces blood cost in long-segment spinal fusion surgery: A randomized controlled study protocol”,


Mol. Biol. Evolut. 2017, 34(8), 1863–1877) attracted a great deal of attention, in particular in conjunction with another paper , 1366–1371), for purporting to discredit the Neutral Theory of Molecular Evolution (Kimura 1968). Here, we address an alleged novelty in Schrider and Kern’s paper, i.e., the claim that their study involved an artificial intelligence technique called supervised machine learning (SML). SML is predicated upon the existence of a training dataset in which the correspondence between the input and output is known empirically to be true. Curiously, Schrider and Kern did not possess a training dataset of genomic segments known a priori to have evolved either neutrally or through soft or hard selective sweeps. Thus, their claim of using SML is thoroughly and utterly misleading. In the absence of legitimate training datasets, Schrider and Kern used: (1) simulations that employ many manipulatable variables and (2) a system of data cherry-picking rivaling the worst excesses in the literature. These two factors, in addition to the lack of negative controls and the irreproducibility of their results due to incomplete methodological detail, lead us to conclude that all evolutionary inferences derived from so-called SML algorithms  should be taken with a huge shovel of salt.In the last 15 years or so, soft selective sweep mechanisms have been catapulted from a curiosity of little evolutionary importance to a ubiquitous mechanism claimed to explain most adaptive evolution and, in some cases, most evolution. This transformation was aided by a series of articles by Daniel Schrider and Andrew Kern. Within this series, a paper entitled “Soft sweeps are the dominant mode of adaptation in the human genome” (Schrider and Kern,  Everyone in the streets said, ‘Oh, how fine are the Emperor’s new clothes! Don’t they fit him to perfection? And see his long train!’ Nobody would confess that he couldn’t see anything, for that would mean that they are fools. No costume the Emperor had worn before was such a complete success.Christian Andersen’s Keiserens Nye Klæder (1837), translated by Jean HersholtHans For most of the history of the population genetics discipline, soft selective sweeps were considered an obscure evolutionary mechanism of little importance in species with large effective population sizes and of no importance at all in species with small effective population sizes, such as human populations. In the last 15 years, however, soft selective sweeps have metamorphosed from a curiosity into a ubiquitous mechanism that has been claimed to explain most adaptive evolution and, in some cases, most evolution in all life forms from viruses to humans (reviewed in Jensen ). A series of articles by Daniel Schrider and Andrew Kern ,4,5,6 weIn this paper, we address a purported novelty in Schrider and Kern’s  paper, iFor purposes of clarity, before further dissecting Schrider and Kern , we outlThe field of machine learning is concerned with the development and application of computer algorithms that improve with experience . Machinea priori, only a posteriori.Unsupervised machine learning methods are designed to identify patterns in the data without training, while supervised machine learning methods, which include support vector machines (SVMs), require a training dataset. Unsupervised machine learning algorithms require only unlabeled input data and the desired number of different labels to assign as input. For example, we may segment the human genome into equal-size segments of length 100,000 nucleotides, collect data on each segment, such as nucleotide composition, mean length of mononucleotide runs, and distance from the centromere, and ask the algorithm to assign each segment to one of five labels or one of 216 labels. We note that none of the labels in unsupervised machine learning can be named Supervised machine learning (SML) algorithms aim to solve two types of problem: (1) the classification problem, whose target is a qualitative variable, e.g., determining whether a gene is expressed or not expressed under certain conditions, and (2) the regression problem, whose target is to predict a numerical value, e.g., the level of gene expression of a gene under certain conditions. In the following, we will only deal with the classification problem. Classification SML algorithms are predicated on the existence of a large set of labeled examples. SML algorithms are trained on labeled examples and are then used to make predictions on unlabeled examples. The set of labeled examples is called the “training dataset”. Classification SML algorithms use what they have learned from the training dataset to make predictions or decisions on a “test dataset”, i.e., a set of unlabeled examples. For example, if we wish to determine whether or not a gene is expressed, we need a “training dataset” of genes for which we have solid empirical evidence on their expression status. We can then unleash the machine learning algorithm on a collection of genes for which expression data is lacking.The immense success that SML techniques have had in the world of e-commerce , as wellWhich type of machine learning should we use? In their influential review of machine learning application in genetics and genomics, Libbrecht and Noble  put forwSML works well when the training data are sufficiently detailed and comprehensive to represent the truth. When the data deviate from this optimum, so will the SML results. When the training dataset does not exist, as is the case in evolutionary studies where the past is unknown, it is impossible to use SML , and unsA hard selective sweep is a process in which a single novel beneficial mutation arises in a population and rises in frequency quickly to fixation. Patterns expected under the hard sweep model mainly include a reduction in variation surrounding the beneficial mutation owing to the fixation of the haplotype in which the beneficial mutation cropped up by chance and well-described effects on the allele frequency spectrum and patterns of linkage disequilibrium. By contrast, a soft selective sweep does not reference a particular population genetic model but rather a collection of many models that may result in similar genomic patterns of variation. Two such models that are banded together within the vague definition of “soft selective sweep” are selection on a preexisting variant in the population that is associated with two or more haplotypes  and selection on multiple new mutations. As far as selection on standing variation is concerned, a selective shift is required, i.e., a variant that was previously neutral or deleterious becomes advantageous. Orr and Betancourt  and HermIn studying the role of adaptation in recent human evolution, Schrider and Kern  claimed Harris et al.  examineda priori to have evolved either neutrally or through soft or hard selective sweeps. Nor can such a dataset ever exist. In the absence of the most crucial ingredient of supervised machine learning, Schrider and Kern [The simplest and most important reason for rejecting Schrider and Kern  is that and Kern  should bOne might, of course, ask what is wrong with simulations? The answer is that there is nothing intrinsically wrong with simulations; they are the bread-and-butter of population genetic research since Francis Galton invented the quincunx or bean machine in 1894. Simulations, however, cannot be used in an SML context because they do not represent data that are known empirically to be true. In other words, simulation results are not true labels. The correct way to use simulated data is to present all the assumptions of the simulation and compare them to the empirical findings. Because of the asymmetry of statistical testing, however, if the empirical values differ from the simulated results, then one or more assumptions used in the simulation can be rejected as unrealistic or untrue; if, on the other hand, the empirical results and the simulated results are identical, the model used in the simulation—especially if it is a complicated model with many variables—can not be said to be true.But, let us assume for a moment (and only for a moment) that simulated data can be used in SML. The appropriate method to test the validity of the results will be to use unsupervised machine learning with five unnamed labels and test whether any of these five unnamed labels coincide with Schrider and Kern’s five genomic classes.delictum, Schrider and Kern piled a large number of sampling transgressions, logical missteps, internal inconsistencies, and corruption of statistical practices, which we present henceforth.The “mortal sin” of using a supervised machine learning algorithm with no training dataset should be enough to invalidate Schrider and Kern’s results and conclusion. However, on top of this Cherry-Picking Population Data. To characterize selection in global human populations, Schrider and Kern [and Kern  had firsK) in the ADMIXTURE analysis [“We see that for most values of K, each of these populations appears to correspond primarily to a single ancestral population rather than displaying multiple clusters of ancestry”.Schrider and Kern  claimed analysis  carried analysis , ExtendeK values, was included, while the more homogeneous British (GBR) and Finnish (FIN) populations were excluded from their analysis. All the three African populations included in the study yield larger and more numerous splits compared to the Esans (ESN), the most homogeneous African population, which was excluded from their study. Finally, the Chinese (CDX) population was excluded despite its genetic homogeneity.An examination of the ADMIXTURE results of Auton et al. shows that Schrider and Kern  frequentK)”, so they “retained this population to have some representation from the Americas”. Oddly, this “exception” clause was not applied to South Asian populations, which represent a considerable fraction of human global genetic diversity. Schrider and Kern  admittedpost hoc to match populations already included in the dbPSHP database [The choice of populations is further questionable on several grounds. First, Schrider and Kern’s  inferencdatabase , which tdatabase : YRI, LWTo summarize, Schrider and Kern  did not Estimating the Parameters of the Demographic Model. To detect sweeps, Schrider and Kern [and Kern  applied and Kern  developeWe emphasize again that unlike in normal SML approaches, where training and testing of the classifier are two separate operations, in Schrider and Kern  the clasEstimating Demographic History from Genomic Data. Before selection can be simulated on the genomic data, Schrider and Kern [discoal to work properly [θ of the population under study  and by the present-day effective population size 0N , and included them in their simulation (the -en parameter)  B. This sand Kern  is robusθ).Estimating The Population Mutation Rate ( The population mutation rate (θ) is a fundamental parameter in evolutionary biology as it measures the average genomic mutation rate of the entire population or, stated differently, it describes the amount of selectively neutral diversity in a population [eN). θ is calculated as 2pNeμtot, where p = 1 or 2 for haploids and diploids, respectively, Ne is the effective population size, and μtot is the mutation rate at the locus of interest. Schrider and Kern [θ ranged from 10 to 250 and was calculated from 4NeμL. Here, μ is the mutation rate per nucleotide, which Schrider and Kern [−8 per base pair per generation as was calculated by Kong et al. [L is the length of the segment.pulation . It is aand Kern  assumed g et al.   were used. In practice, Schrider and Kern [θ values that ranged from 40 to 2200  since they chose “as the final values of θ that for which the sum of the percent deviations of the simulated from the observed means of each statistic was minimized.” By inflating the range of θ, Schrider and Kern [Confusingly, multiple le S5 in ); 2,200,le S5 in  neither ans from , θ shouleN).Estimating the Effective Population Size  and the published L value  yields a remarkable eN range of 8333 < eN < 458,333, i.e., values similar to those of Plasmodium falciparum  and Drosophila melanogaster  [L value   results in an extreme range for eN 757 < eN < 41,666, compared to the eN calculated by Auton et al. (1500 < eN < 4250) [eN < 10,000) , excepting Central chimpanzee  [eN, Schrider and Kern [150,000) . Even us < 4250)    . By inflρ).Estimation of the Population Recombination Rate  indicates, again, that different values of ρ were used . According to that table, the mean of the exponential distribution ranged from 183 to 1008. d Kern’s  analysesof 10−4  and the subdivision into windows is part of a different package, called S/HIC . To understand whether these numbers are reasonable, we downloaded the CEU data from the 1000 Genomes Phase 3 (v5) [discoal simulations. In other words, the number of SNPs in the simulated discoal sequences is less than half than in reality.To name a few examples, Schrider and Kern  wrote thdiscoal  to simule 3 (v5) . We samp“we simulated additional test sets of 1000 genomic windows 1.1 Mb in length with varying arrangements of selected sites”, without telling the reader which simulation tool they used. In another place in the article, the authors wrote, −8 [“The simulation program discoal requires some of these parameters to be scaled by the present-day effective population size; we did this by taking the mean value of θ and dividing by 4 uL, where u was set to 1.2 × 10−8 . The ful This section describes the use of at least three tools with only discoal referenced explicitly. It remains unclear how many regions were simulated since parts of the manuscript mention 100 kb and other parts mention 1.1 Mb. Adding to the confusion is that the code (their Table S5) simulates 200 kb regions but employs parameters calculated for 1.1 Mb regions. Another typical paragraph reads: Bypassing Training Data by Importing Random Annotations. Since Schrider and Kern [and Kern  lacked aInnovatively, the authors devised the following quick fix to this seemingly intractable problem. They randomly selected 1.1 Mb regions from the human genome and used public datasets, such as phastCons, to annotate them. In the next stage, they generated a random sequence and copied the annotation of the real sequence onto the simulated one. For example, if the authors selected the region chr1:55000000–56100000 and if there was a conserved phastCons element at chr1:55000000–55000009, then the first ten bp of the simulated region would be marked as negatively selected . At no time were actual nucleotides from the human genome considered. Classifying the Simulated Sequences into Five Classes. Schrider and Kern [and Kern  applied The authors are very unclear about how the classifier’s decisions were made. For instance, they write: “For our classifications we simply took the class that S/HIC’s classifier inferred to be the most likely one, but we also used S/HIC’s posterior class membership probability estimates in order to experiment with different confidence thresholds”. We interpret this statement to mean that irrespective of the class inferred by the S/HIC classifier, the authors chose any threshold they fancied to make the final class determination. Schrider and Kern  argued tThere are other problems with the S/HIC classifications, one of which is that “adjacent windows are especially likely to receive identical annotations . To overTo summarize, Schrider and Kern’s classification of genomic regions into classes required not only an SML classifier but also a human intervention in the form of setting subjective thresholds that ranged widely in value. These thresholds, in turn, generated preconceived results that lack any scientific merit.Identifying Genetic-Element Enrichment in Selective Sweeps. To complete their study that rests entirely on imaginary sequences onto which random annotations were thrust upon, Schrider and Kern [and Kern  ask whicand Kern , which, and Kern . Anotherand Kern . Admitteand Kern  came to and Kern , with a One such example of functional futility involves Schrider and Kern’s  “dramatiprima facie seem remarkable. For example, of the 19 annotated features, the CEU population (Utah residents with Northern and Western European Ancestry) showed no significant enrichment for any annotation except “enhancers lost in humans since splitting with rhesus.” By contrast, all the other populations showed significant enrichment of more than 50% of the annotated features . The aule S3 in ). As in “unfounded enthusiasm for soft selective sweeps in the evolutionary literature.” In particular, Jensen [Ns < 50,000), the correct model is identified in fewer than 5% of simulated replicates, while hard sweeps were incorrectly classified as soft sweeps in nearly 50% of the replicates, as linked soft sweeps in 16% of the replicates, and as neutrally evolved sequences in 31% of replicates. In other words, under their own estimated demographic history, Schrider and Kern’s [Jesnsen  and Harr, Jensen  noted th, Jensen  carried , Jensen . They fi, Jensen , alreadyd Kern’s  found thThe distribution of fitness also affects S/HIC’s predictions. When the selection in the training set is stronger than in reality, S/HIC overwhelmingly classifies hard sweep windows as soft. When the range of selection  is weaker than in Schrider and Kern , 47% of hard sweeps are misclassified as soft, and 46% of hard-linked sweeps are misclassified as soft-linked [Here, we have shown that SML is inherently inapplicable to exploratory studies on evolutionary questions related to the driving forces of evolution for the simple reason that true empirical training datasets do not exist. As far as the study by Schrider and Kern  is conce“an excellent example of how cutting-edge methods from computer science and statistics can be successfully brought to bear on long-standing questions in evolutionary biology” [Despite claims to the contrary, Schrider and Kern  have notbiology” . What thbiology”  predictebiology”  study co“the growing tendency of invoking parameter-heavy, assumption-laden models of pervasive positive selection, and neglecting best practices regarding the construction of proper demographic null models.” The purpose of Schrider and Kern’s “machine learning” is to create the appearance of sophistication, of doing something extraordinarily clever and original, so that anyone who challenges their work can be cowed into submission or be labeled stupid. Fortunately, the authors of this note are familiar with the parable in The Emperor’s New Clothes.Our findings are similar to those of Harris et al. , who war


Having a life partner significantly extends survival for most cancer patients. The label given to the partners of cancer patients may, however, influence the health of not just the patients but their partners. “Caregiver” is an increasingly common label for the partners of patients, but it carries an implicit burden. Referring to partners as “caregivers” may be detrimental to the partnerships, as it implies that the individuals are no longer able to be co-supportive. Recognizing this, there has been some effort to relabel cancer dyads as “co-survivors”. However, many cancer patients are not comfortable being called a “survivor”, and the same may apply to their partners. Cancer survivorship, we argue, could be enhanced by helping keep the bond between patients and their partners strong. This includes educating patients and partners about diverse coping strategies that individuals use when facing challenges to their health and wellbeing. We suggest that preemptive couples’ counselling in cancer centers may benefit both patients and their partners. One of the most established facts in cancer epidemiology—and, for that matter, most of medicine—is that having a long-term and stable spousal relationship means better outcomes for the patient. This was documented for 10 major cancers by Aizer et al. back in 2013, in his study of married patients ,5,6,7,8.Here, we review labels that have been given to the partners of cancer patients and explore the idea that the labels themselves could impact the partners, the patients, and their partnership. We focus on what may be implicit but unstated messages in those labels. We suggest that healthcare providers be cautious about the labels they use in referring to the partners of patients and be attentive to the terms that are most helpful not just for the patient, but also for the dyad. We also offer strategies for helping couples maintain co-supportive partnerships in the face of cancer.Clearly, many partners positively benefit from supporting their loved ones , howeverIt should be noted that we are not referring to healthcare providers, nor to parents or guardians, who can all be caregivers under the broad umbrella of “support providers”. Rather, we are referring specifically to the long-term  partners of cancer patients.The orange line in Recognizing the great emotional burden to spousal partners brought on by their partner’s cancer diagnosis, some authors have suggested replacing the couplets “patient and partner” and “patient and caregiver” with the term “co-survivors”. The term “co-survivor” used in this context is relatively new; it shows up in the oncological literature less than a half-dozen times before 2000.The term, however, has not gained much popularity in this century. A Google Scholar search for “cancer” paired with the word “co-survivor(s)” (with or without the hyphen and with or without the “s”) yielded < 250 results as of October 2021. This pales in comparison to the 197,000 hits acquired with the search combination “cancer” and “caregiver(s)” .Many cancer patients are themselves not comfortable with the label “survivor” ,11,12. ISimply labelling a couple as “co-survivors” fails for three reasons. First, the term has never been in common use. Secondly, patients themselves may not be comfortable being labelled “survivors” and it is reasonable to suppose that that discomfort would carry over to their partners. Lastly, patients and partners may understand the word “survivor” to imply that a cancer that was life-threatening is being cured, and they may reject the term if they have different perspectives on those matters.Labels that are used for any dyad can variously reflect similarities or differences between the individuals in the dyad. On one hand, the term “co-survivors” focuses on the equality and similarity of the individuals so labelled. On the other hand, “patient and caregiver” flags the inequality and dissimilarity between the individuals. “Patient and partner” is a more neutral term.We favor the label “patient and partner” for its neutrality, but we recognize that serious illnesses and their treatments are stressful for both patients and their partners. As such, dealing with cancer can accentuate a couple’s shared concerns and bring partners closer together. Alternatively, though, major stressors can bring to the surface differences in how partners handle stress… and drive them apart.How cancer and its treatments affect a couple’s dynamics often rests on how the individuals cope with stress. Recognizing and respecting differences in coping styles can be key to keeping a patient and partner co-supportive of each other and, thus, a strong dyad.Several studies have documented that the stress of a cancer diagnosis can be greater on the partner than the patient, particularly for female partners . Women rPartners may have divergent and even conflicting adaptive strategies for dealing with illness, and this can challenge their partnership . For exaIn the worst of situations, a partnership that was unstable before the cancer diagnosis can become unbearable for the patient, the partner, or both. This stress can lead to separation or divorce. That, in turn, has further negative consequences on the survival and quality of life for the patient. This has been documented in another Aizer-coauthored paper, which found that recently divorced cancer patients had lower cancer-specific survival than long-term married patients .Aizer et al. 2013) pointed out that being married  has more of a survival benefit than chemotherapy for five of the ten major cancers they examined  pre-existing relationship[s] through the terminology they use” . That stAlthough many spousal partnerships will end up as patient-and-caregiver partnerships, treating patients and the partners as co-supportive spouses is good cancer care because strong dyads mean better outcomes overall.


A consensual definition of occupational burnout is currently lacking. We aimed to harmonize the definition of occupational burnout as a health outcome in medical research and reach a consensus on this definition within the Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET).First, we performed a systematic review in MEDLINE, PsycINFO and Embase (January 1990 to August 2018) and a semantic analysis of the available definitions. We used the definitions of burnout and burnout-related concepts from the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to formulate a consistent harmonized definition of the concept. Second, we sought to obtain the Delphi consensus on the proposed definition.In a worker, occupational burnout or occupational physical AND emotional exhaustion stateis an exhaustion due to prolonged exposure to work-related problems”. A panel of 50 experts  reached consensus on this proposal at the second round of the Delphi, with 82% of experts agreeing on it.We identified 88 unique definitions of burnout and assigned each of them to 1 of the 11 original definitions. The semantic analysis yielded a first proposal, further reformulated according to SNOMED-CT and the panelists’ comments as follows: “This study resulted in a harmonized definition of occupational burnout approved by experts from 29 countries within OMEGA-NET. Future research should address the reproducibility of the Delphi consensus in a larger panel of experts, representing more countries, and examine the practicability of the definition. Despite more than half a century of research on occupational burnout, little is known about its prevalence, etiology, treatment, or prevention. The lack of consensus on the nature of burnout has led to a proliferation of definitions and measures of the construct . This stburn-out” was introduced in the 10th revision of ICD (ICD-10) without any definition  should be considered as synonymous with another, already known term or expression (the definiens) . In fact, the term burnout was originally introduced using an ostensive definition  . The onlfinition , and onlfinition  and manyGiven this situation, we aimed to  formulatWe conducted this research in two parts. First, we performed a systematic review of all existing definitions of occupational burnout and a semantic analysis of the 11 original definitions. We used Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) definitions of burnout and burnout-related concepts to propose the terms and a definition of the concept. Secondly, we sought to obtain consensus on our proposal using the Delphi technique , 18.Search strategy and selection criteria. The search was conducted within the context of a broader systematic review, aimed at addressing all causative predictors of burnout in workers (PROSPERO CRD42018105901) (8105901) . We searWe included original research focused on workers, published in European languages between 1990–2018 in peer-reviewed journals. Among them, we selected studies which (i) examined the relationship between exposure to any kind of factors  and the onset of burnout; (ii) used a longitudinal design, (iii) assessed exposure before the onset of burnout, and (iv) had a minimum of 50 participants per exposed group. When multiple publications described the same study, we included the publication with the most complete reporting of study results. We conducted a double screening of relevant studies: the first screening was based on the title and abstract of all publications identified through the literature search. All studies which met the inclusion criteria, or for which it was not possible to check these criteria, were included in the second screening, which was based on reading the full text. The literature corpus was equally allocated between the 14 OMEGA-NET reviewers. In parallel, the second reviewer independently read all the studies. Therefore, two independent reviewers conducted both screenings. A third reviewer helped resolving disagreements.For this study, OMEGA-NET reviewers extracted for each study: the reference, year of publication, definition of burnout as formulated by the authors  and the source(s) of this definition ) using a standardized data extraction form (MS Excel). The first and second authors double-checked all extracted data.The referenced and used definitions were split between original definitions  and secondary definitions . All definitions  constituted the corpus of our semantic research. However, the analytical sub-corpus only included the original definitions and two additional definitions published after the completion of the literature search , 21.We conducted the semantic analysis in three phases: In phase 1, we examined the concepts and their expressions in terms of hyponymy and hyperonymy, corresponding to the lower (more specific) and upper  levels in the concept’s semantic hierarchy, respectively. We selected hyponyms and hyperonyms occurring/recurring in at least three different definitions. The choice of this number is arbitrary, but justified, as the choice of a low number prevents the loss of potentially interesting information. We considered that the (hyponymic or hyperonymic) terms that appeared only once or twice were too specific and hence not worth taking into account. Definitions of burnout were all structured in a heterogeneous way and described in the form of (i) a list of simple terms , (ii) a list of nominalizations with some specifications , but also (iii) in a more discursive way . We also considered discursive descriptions as lists of elements, so that, for example, “they lose all concern” can be interpreted and evaluated as “loss of all concern”. In this way, single terms and multi-word expressions can be considered as isolated semantic elements, independently from a specific and actualizing syntactic context.In phase 2, we reorganized the results of phase 1 into the ideal structure for the medical description of burnout as a syndrome, ie, a multi-level conceptual framework based on symptoms. To enhance the precision of the level to which symptoms should be attributed, we excluded all information about the context of burnout development and the specific population prone to burnout, which were in the definitions.In phase 3, we calculated the effective presence of each element on each level, in each definition. We deduced a semantic proposal of a definition of occupational burnout based on shared elements .Furthermore, we consulted the last release (July 2019) of SNOMED-CT International Edition for the terms “burnout”, “exhaustion”, and “occupation” and extracted their definitions and the definitions of their hyperonyms and hyponyms. We summarized the extracted information and formulated a definition proposal based on SNOMED-CT’s terminology, following the fundamentals of medical concept formation .We considered as experts all members of OMEGA-NET and external experienced health practitioners with ≥10 years of practice and knowledge of occupational burnout. We used purposive sampling among OMEGA-NET members and snowball sampling with the external health practitioners. The latter method was implemented through the national focal points of the European Agency for Safety and Health at Work (EU-OSHA)  and OMEGa priori defined the consensus valid if at least 75% of participants rated the definition ≥7 on a 9-point Likert scale  and ’occupational burnout’ (term 2). We defined it as follows: ““In a worker, occupational burnout or occupational physical AND emotional exhaustion state is an exhaustion due to prolonged exposure to work-related problems”. This definition received 82% of grades ≥7, and was consensually approved in the second round.Among the 100 experts invited, 60 formally agreed to participate. A high participation rate in the first and second rounds  maintained the panel composition stable in terms of the characteristics considered . The proThe harmonized definition of occupational burnout that emerged from this study looks extraordinarily simple but responds to the fundamentals of definition formation. It is a conditional definition because the application of the concept introduced by the definition is conditional on specific circumstances, such as having an occupational activity, as indicated in the definition by the expression ’in a worker’. In general, a term introduced by a conditional definition cannot be replaced by its definiens in all contexts . TherefoThe term ’work-related problems’ deserves discussion, as it was strongly debated among panelists. The challenge was to find a well-defined term that would cover most, if not all, work-related stressors or risk factors. In this respect, the concept ’problems at work’, defined in SNOMED-CT as an attribute of ’work and retirement-related problems’, was considered the best option. The concept ’problems at work’ has 12 hyponyms and involves 7 additional, more specific concepts, including ’discord in the workplace’, ’uncongenial work environment’, ’stressful work schedule’, and ’difficulty adjusting to work situation’ . Not allRegarding the meaning of the word ’problem’, we consulted three dictionaries to consider possible negative cultural perceptions associated with it. The Oxford English Dictionary (OED) defines a problem as “a difficult or demanding question; a matter or situation regarded as unwelcome, harmful, or wrong and needing to be overcome; a difficulty.” The Webster dictionary, defines a problem as “1a: a question raised for inquiry, consideration, or solution; b: a proposition in mathematics or physics stating something to be done; 2a: an intricate unsettled question; 2b: a source of perplexity, distress, or vexation; 2c: difficulty in understanding or accepting.” Finally, Cambridge Academic Content Dictionary, defines a problem as “a1: a situation, person, or thing that needs attention and needs to be dealt with or solved.” These three definitions, and in particular Webster’s definitions 2b and 2c seemed to fit pretty well the ’concerns’, ’constraints’, ’issues’ and ’situations’, mentioned by some of the experts, which could be all summarized using the term ’problems’. None of the other terms better fits our context as they are not well-defined terms within the SNOMED-CT and are subject to a wide interpretation according to the cited dictionaries. Therefore, the terms ’problems at work’ and ’work-related problems’ appeared to be the most convenient and clearest terms available. Indeed, they cover a large set of situations and have an extensible list of hyponyms, allowing for the introduction of new concepts corresponding to the additional work-related risk factors, if necessary. Finally, the term ’prolonged’ was added to the final definition as all the panelists agreed that it is important to specify the duration of exposure as part of necessary causal condition. The choice between the qualifiers ’chronic’ or ’prolonged’ to the term ’exposure’ was debated. According to SNOMED-CT, the terms ’prolonged’ and ’chronic’ are not synonyms. The term ’prolonged’ is defined as a qualifier value of duration and has no synonyms, while the term ’chronic’ is defined as a qualifier value of courses and has an acceptable synonym ’chronic course - prolonged duration’. In the OED, ’chronic’ is defined as “Lasting a long time, long-continued, lingering, inveterate; opposed to acute. Continuous or constant.” While ’prolonged’ is defined as “Of extended duration; protracted. Frequently with negative connotation. Extended, lengthened in space.” As exposure should not necessary be constant to result in a burnout, it appeared preferable to use the term ’prolonged’ to complete the definition. The timespan of ’prolonged’ still remains to be addressed. We believe that it would be possible, at least partially, in the systematic review of burnout predictors (in progress) and in the near future.If accepted more generally, this definition may reduce the semantic chaos surrounding the concept of occupational burnout and improve medical research, treatment and prevention of this outcome. It may also clarify whether burnout should be classified as a disease , 46. In This study has at least three limitations. First, in order to select only studies of the highest quality with a documented definition of burnout in workers, our semantic research corpus excluded cross-sectional studies, studies published in other databases, and the grey literature, We identified 88 unique definitions in 248 studies. On the other hand, Rosenstein et al  reviewedSecond, our expert panel only represented countries that are part of OMEGA-NET. Therefore, we cannot speculate on the reproducibility of the experts’ selection and the representativeness of our panel in other countries. The use of a randomized sampling method for expert selection was not possible, but all EU-OSHA national focal points have a network to provide input to the EU-OSHA’s work and to disseminate products and information to national stakeholders. They presumably used this network to identify experts and assess their eligibility. External experts represented 45% of the panel and our statistical analysis showed that Delphi results were independent of the OMEGA-NET membership and other characteristics of the experts. Lastly, the size of our expert panel was not very large. This can affect the stability of the results. However, few Delphi studies on mental health had >50 experts .Third, we conducted our literature review up to 2018. Although no new definition of burnout has been introduced in the scientific literature since then, several factor-analytic studies have recently concluded that burnout—and most notably, exhaustion—was reflective of a depressive condition , 48. BecFuture research should address the reproducibility of our results in a larger expert panel, representing more countries, and examine the utility of the formulated definition of burnout for researchers and practitioners.