Information and Communications Technologies (ICTs) which enable people to access, use and promote health information through digital technology, promise important health systems innovations which can challenge gatekeepers’ control of information, through processes of disintermediation. College students, in pursuit of sexual and reproductive health (SRH) information, are particularly affected by gatekeeping as strong social and cultural norms restrict their access to information and services. This paper examines mobile phone usage for obtaining health information in Mirzapur, Bangladesh. It contrasts college students’ usage with that of the general population, asks whether students are using digital technologies for health information in innovative ways, and examines how gender affects this.This study relies on two surveys: a 2013–2014 General Survey that randomly sampled 854 households drawn from the general population and a 2015 Student Survey that randomly sampled 436 students from two Mirzapur colleges. Select focus group discussions and in-depth interviews were undertaken with students. Icddr,b’s Ethical Review Board granted ethical clearance.The data show that Mirzapur’s college students are economically relatively well positioned, more likely to own mobile and smart phones, and more aware of the internet than the general population. They are interested in health information and use phones and computers to access information. Moreover, they use digital technology to share previously-discreet information, adding value to that information and bypassing former gatekeepers. But access to health information is not entirely unfettered, affecting male and female students differently, and powerful gatekeepers, both old and new, can still control sources of information.Personal searches for SRH and the resultant online information shared through discrete, personal face-to-face discussions has some potential to challenge social norms. This is particularly so for women students, as sharing information may enable them to bypass gatekeepers and make decisions about reproduction. This suggests that digital health information seeking may be exercising a disruptive effect within the health sector. However, the extent of this disruption may depend, not on students’ mobile phone usage, but on the degree to which powerful new gatekeepers are able to retain control over and market SRH information through students’ peer-to-peer sharing. Innovations in Information and Communications Technologies (ICTs), and especially mobile health, have been predicted to transform provider-patient relationships through the dissemination of health information, and by encouraging patient autonomy, self-management, and self-care . People’College students, as young adults in pursuit of sexual and reproductive health (SRH) information, encounter health system – and other – gatekeepers who control access to information , 54). InThe concept of a ‘digital divide’ captures the relationship between technological innovation, inequality and exclusion along the lines of gender, educational attainment and income . HilbertMobile phones and digital technology offer new ways of bypassing gatekeepers and innovative means of accessing health information, leading to what some commentators have heralded as ‘digitally engaged citizens’ – people accessing, using and promoting health information through digital technology unencumbered by intermediaries, and gatekeepers; a process termed disintermediation , 37. ThiThis liberatory potential and the opening up of previously-controlled information, Eysenbach  hypothesPositive health system innovation extends beyond the public provision of health information through technology and the elimination of those gatekeepers whose access to knowledge and resources inhibits healthy and informed choices. The information provided has to be appropriate and any corresponding treatment efficacious. Health systems must retain the capacity to manage public health, while bearing in mind broader public goods and positive externalities that result from health system delivery. They need to accredit and regulate professional behaviour and ensure that medical providers, who may have their own prejudices and biases, do not exploit unequal power relations . UltimatIn Bangladesh, the health system comprises a complex mix of formal government and private facilities and a large and diverse range of informal providers, resulting in a range of experts and intermediaries , 26, 42.Internet.org which allows people access to ‘25 government and private websites’ through mobile phones  examinations”.“As Anita  explains,Similarly, Poly owned a phone, but her family did not allow her to use it until after her exams. Even when young women owned phones and were allowed to use them, they tended to leave them at home and, when asked, gave the socially-approved response that mobile phones were frivolous whereas they were hard-working students.Table 11mobile browsing’, as it was called, from friends, older brothers or cousins and, in the case of young women, their school teachers. Initially they played games, and downloaded music and videos. Their colleges also used the internet to communicate with them. Facebook (discussed in more detail below) is also a popular form of internet use. In Bangladesh, Facebook is necessary for college study activities as class schedules are posted here and it also offers newsfeeds, a source of jokes or other topics of interest, and ways to make new friends  said if I use Facebook, I would walk in the wrong path’. However, as discussed further below, both male and female students report using mobile phones in ways which demonstrate potential for innovation and disintermediation. This suggests that women college students are able, at least to some extent, to bypass societal controls on their mobile phone usage.Internet usage among college students is gendered. When asked about usage in the past month, men were twice as likely as women to have done so Table . This isto chat to friends’, and as one informant told us, to be “more connected through these. It’s comfortable and a lot of people appreciate it”.When asked how they had used the internet in the past month Table , studenton my Facebook, with my ID there are a lot of health pages. I like them. Whichever comes in front of me, whenever I find this is a health page or treatment page I will ‘like it”. Other students ‘liked’ and read pages on heart attacks, home treatments for coughs, or flu symptoms. One student ‘liked’ the posts his friends ‘liked’. Through Facebook, accessed ‘free’ as part of their credit bundles, they could visit these health-related websites: MAMA,Maya.com.bd,HealthPrior21.comAlthough students are using mobile phones and the internet far more than the general population of Mirzapur, only 12% of students surveyed reported having used the internet specifically to search for health information. Most common usage of the internet was through Facebook and Google Table . AlthougTable problems that we can’t tell in front of others’, not least because: ‘if I ask [health providers or other gatekeepers] something who knows what they’ll think, but the internet won’t think anything. The internet is for giving information’. Using phones and the internet in this manner echoes the privacy provided when medicinal drugs are treated as ‘things’ liberated from medical regulation and specialist oversight and can, as such, be obtained as ‘common commodities … purchased like other daily wares in shops and markets’ . Women college students also mentioned searching for SRH information on menstruation, pregnancy, and contraception; while men students emphasised topics such as HIV, and sexual intercourse. Internet use avoided their embarrassment of ‘arkets’ (: 123). Markets’ ; how to manage menstruation; sexual relations after marriage and how pregnancy happens. College students most common health-related phone activities were to contact informal healers such as village doctors (18%), contact medically-trained doctors (17%) and make appointments with doctors . Amongst the general Mirzapur population, the most common use of mobile phones for health purposes was to contact a doctor (9%) and to get advice on a treatment or condition (8%), although considerably fewer did this than in the student population. College students also used their phones to get advice on a condition or to secure treatment . This suggests that students are interested in using mobiles to access health help lines and new ICT-based government health services.by the time we search for something and the results come up, we could have reached the hospital’, suggesting it was faster to get professional help than to go looking online for health information.Nonetheless, internet usage remains low amongst college students because of the lack of bandwidth, lack of internet-connected computers and laptops, poor network coverage, lack of 3G, and frequent network collapse, all of which undermine the value of online searches. Indeed, as one student commented ‘There is evidence that college students use the internet when they need broader health information. A higher proportion of students who had cause for concern found something on Facebook’ saying that garlic is beneficial for asthma and told his friends and family. ‘Now everyone’s having garlic and getting benefits’ despite not suffering from asthma. In these instances, there is scope to use non-biomedical health information, but this may be less appropriate if faced with more serious health conditions (discussed in more detail below). Both men and women students also browsed for information on sex, and what to eat to keep fit. Women students were interested in understanding reproduction and controlling fertility, while male students looked at pornography and searched for information on prolonging intercourse. As one male informant explained, ‘well I have searched a bit [for SRH information]. Now if you talk about pornography, even people 5 years younger than us watch porn regularly… They’re watching it on the phone, on the laptop, it’s everywhere’.In interviews and FGDs, all college students, both male and female, spoke about their interest in skin care, fitness and diet and how the internet gave them access to this health information. Not all the information received was biomedical. For example, worried about the condition of his hair (slow growth and thinning), Ishrat used Google and followed advice suggesting he apply a mixture of castor and coconut oil. This, he believed, solved his problem. Johnny ‘good’ and ‘well-reputed’ doctors online after his mother’s car accident, and for his grandfather’s kidney problem . Shafwat tried (unsuccessfully) to call a health help line to enquire about his younger cousin’s loss of appetite.everything’. With the exception of Ishrak, none of these students acted on the online information and seldom shared it with their families. As a consequence, online health information did not usually translate into particular health seeking behaviours.Some male students had used the internet for other family members’ serious health problems. Ishrak made an online medical appointment at a hospital in Dhaka for his mother’s eye problem. Johnny identified ‘no idea about it’ and said, ‘I knew about it when I first experienced it… I was not informed by anyone [about menstruation]’. Others, like Bithi, researched menstrual pains for herself and pregnancy advice for another. Nisha Googled contraception.Female students (most of whom were unmarried) searched online to find out about their bodies and sexual health. They spoke of their difficulty discussing these issues with doctors  and other adult women. Even though societal norms discouraged young women students from accessing SRH information and from ‘frivolous’ mobile phone usage, these students emphasised their newfound ability to use their phones (often without their parents’ knowledge or permission) to avoid gatekeepers. Some searched for information on menstruation. Fatima for example, had ‘The data show that Mirzapur’s college students are economically relatively well positioned, more likely to own mobile phones, and more aware of the internet than the general population and youth in the general population Tables –4. TheseThe concept of disintermediation imagines a process of unmediated access to information, which enables people to navigate around gatekeepers, retrieving information which is usually controlled by professional interest groups of various kinds. Evidence from Bangladesh, however, points to the importance of social and cultural gatekeeping in a conservative society, with constraints (stricter for women and unmarried men) on young people’s sexual health information. Young people trying to get information on issues such as sexual and reproductive health thus often have to overcome barriers imposed by a wide range of health gatekeepers, including family, elders, guardians of socio-cultural knowledge, health system providers and medical experts, as the keepers of medical knowledge and what it is ‘appropriate’ for them to know, and as decision makers about access to services and treatment. The reality in Mirzapur is therefore far from a utopian world of disintermediation and apomediation. While both male and female students looked for health information online – from how to care for one’s skin to what to do about tumours – and were able to access some information, there were limits to what information they accessed and how they could use it. Lupton, focusing on ‘digitally-engaged patients’, argues that digital technology and disintermediation should provide the means of ‘preserving and promoting their own good health, including accessing relevant information, monitoring their own health and taking responsibility for managing their medical conditions’ (: 857). Ifull or entire analysis’. While access to this information provided Nisha with some reassurance, it may not have been a complete and medically-accurate analysis and there are few guarantees that she will be able to delay pregnancy as a result of this knowledge.Nevertheless, in Mirzapur, access to digital technology offered college students ways to evade some gatekeepers’ social control and, in so doing, to make health and SRH information more freely available to them. Sexual health is an area where gatekeeping is particularly prevalent. Conventionally information about SRH was seldom shared between adults and students, and particularly not between adults and young women There are, of course, potential disadvantages associated with the bypassing health professionals and other traditional gatekeepers. Van der Geest and Reynolds Whyte  examine To date, however, access to the internet, usually through mobiles and occasionally computers, has provided male and female students in Mirzapur with discretion and anonymity, factors which, for youth, may be more important to them than health providers’ qualifications  and biomSuch actions facilitate apomediation, the process by which college students use digital technology and, having become educated about their bodies and health conditions, share knowledge with their peers, and provide information to family members when relevant . ApomediIn theory disintermediation and apomediation provide college students with greater choice as to who might offer health information. Some may continue to use the intermediaries they have always used. Others might look to new intermediaries. The tendency to look for new intermediaries, Eysenbach suggests, is particularly pronounced among young people who, ‘strive to become more autonomous and to reduce the power of intermediaries such as their parents, with peers taking on the role of the former intermediaries’ (: 162). OOur study shows that willingness to engage in disintermediation and apomediation is influenced by age, gender, health condition and by familiarity with digital technology. Despite young men having greater access to digital technology, college students of both genders are using phones and computers to explore sexuality and healthy lifestyle choices. This information is relatively easy to act upon, not requiring significant social and financial resources. Mirzapur’s students found online information to be useful and engaged, to some extent, in peer apomediation, sharing health information in face-to-face discussions with friends and similarly-aged relatives who were not as experienced online, and through ‘likes’ and forwarding posts.Familiarity with technology also influences the extent to which college students use digital technology as a means to bypass intermediaries. Thus, the more intensively students used mobiles, the less likely they were to defer to their parents as the primary health intermediary. There is, as shown above, a dominance of male students among internet users, reflecting both lower levels of familial gatekeeping and their greater access to the internet. This, Eysenbach  suggestsIf you have any problem, you will find a separate page after logging into internet’. So, when Shaninoor was interested to find out more about contraception, she remembered ‘Sir told us that if there are any health or questions like that… Sir gave us an address, so I searched by typing that’. At the time of the interview, Shahinoor had never searched on Google, she had only used the website address given to her by her teacher. Bithi’s teacher, equally embarrassed to teach biology, had said ‘you can find anything if you Google it’ and thus encouraged her to explore health and reproductive information online. Bithi then searched for health information online, finding information and downloading health apps.There are also new intermediaries, such as digital providers and college teachers that – whilst embedded in conventional socio-cultural systems and power relations – allow the possibility of bypassing gatekeepers. College teachers are required to teach SRH in schools . Socio-cDigital service providers in the telecommunications industry also act as new gatekeepers to health information through the types of internet access and bundles they offer. Social network providers such as Facebook provide information to members through, for instance, selected links which direct college students, and other young people, to particular websites. In so doing, Facebook offers an illusion of using the whole internet, but this is limited to particular sites. As indicated in the following quotations, at least some of Mirzapur’s college students, both male and female, do not recognise this distinction and associate internet searching with Facebook:How long have you been using the internet’? Respondent: ‘I’ve basically been connected to the internet because of Facebook. Since 2012, it could be said’.Interviewer: ‘So which medium do you use to get information’? Respondent: ‘… for the exchange of information I use the internet, mainly Facebook browsing’.Interviewer: ‘This limited access undermines the concept of the internet, which is to enable anyone to connect up to anyone else without gatekeepers and without permission. ‘The internet by definition is a vast collection of interlinked sites – over a billion of them, at last count. And Facebook offers about 0.0000002% of this to the user’ , nAlmost two decades ago, Goldsmith predicted that ‘the internet has a greater potential to fundamentally transform both the structure and the core processes of medicine than any new technology we have seen in the past fifty years […] The most important effect of the internet will be to strengthen the consumer’s role in relation to practitioners and health care institutions, and to create a powerful new tool to help people manage their own health risks more effectively’ (: 155–6).Disintermediation has taken place to varying degrees with both male and female students searching online for health information. The ways in which college students share information online, through ‘likes’, forwarding posts etc., is more in keeping with what one might expect in this era of digital innovation. Yet it is perhaps the personal searches for sexual health, undertaken by both women and men, and the information found online but shared through discreet, private and personal face-to-face discussions, that most challenges social norms and is perhaps most innovative. This is perhaps most radical in the case of some young women students because it provides them with information which facilitates decisions about reproduction that were previously in the hands of senior women, men and health service gatekeepers.Using mobile phones to access the internet was something college students were doing in relation to sexual health and lifestyle information, and was an activity which enabled them to bypass intermediaries and gatekeepers; but was not an activity undertaken in critical health situations. To what extent then, does this digital health information seeking portend future innovation and disruption in the health system?The evidence of disintermediation and apomediation suggests that changes in access to health system knowledge and power relations are likely but will still have to contend with the power of social and cultural norms. There is evidence that familiarity with digital technologies enhances the likelihood that conventional gatekeepers will be circumvented and that, even as new intermediaries emerge, new sources of information will be promoted which are less grounded in socio-cultural norms and power relations, but access is still likely to be gendered and to be subject to policing by family members or by other social and political forces. The data suggest that apomediation and experience-based credibility may become increasingly desirable and relevant but that this will raise important questions about the quality and reliability of information and how these are ‘brokered’. Because these college students are likely to continue using digital technology as they age, improvements in their technological skills, in the technology itself, and in access to the technology are to be expected. Ultimately however, large-scale health system innovation may depend not on the innovations used by college students, but rather on the degree to which powerful internet gatekeepers – such as Facebook – are able to dominate control over SRH information while marketing seemingly unmediated health information and treatments in the guise of peer-to-peer apomediation.


Jules Cotard described, in 1880, the case of a patient characterized by delusions of negation, immortality, and guilt as well as melancholic anxiety among other clinical features. Later this constellation of symptoms was given the eponym Cotard's syndrome, going through a series of theoretical vicissitudes, considering itself currently as just the presence of nihilistic delusions. The presentation of the complete clinical features described by Cotard is a rare occurrence, especially in the context of schizophrenia. Here we present the case of a 50-year-old male patient with schizophrenia who developed Cotard's syndrome. The patient was treated with aripiprazole, showing improvement after two weeks of treatment. A review of the literature is performed about this case.  Société Médico-Psychologique entitled Du délire hypocondriaque dans une forme grave de la mélancolie anxieuse, in which he described the case of a 43-year-old woman who claimed to have no brain, nerves, stomach, or soul and whose belief was that neither God or the devil existed, thus avoiding the need to eat and existing eternally until she was burnt [ délire hypocondriaque resulted from a “…delusional interpretation of the pathological sensations experienced by patients suffering from common anxious melancholia” [ lypémanie, whose original features Cotard described as (a) melancholic anxiety, (b) condemnation or possession ideas, (c) suicidal behavior and voluntary mutilation, (d) insensitivity to pain, (e) nonexistence ideas involving the whole body or any of its parts, and (f) delusions of immortality, being these the original clinical features Cotard described [ délire hypocondriaque happened when the délire des negations had been established: “I propose the name of delusions of negation to assign the condition of patients… in which the negative disposition has reached its highest level… have no head, nor stomach, some even have no body; if they are shown any object, a flower, a rose, they reply: it is not a flower, it is not a rose. In some of them, negation is universal, nothing exists anymore, they themselves are nothing,” “When the delusion of negation has been established, it aims at the patient's personality; the external world… adapts a hypochondriac form” [On June 28, 1880, Jules Cotard gave a lecture at theac form” . délire des negations as nihilistic delusion has given the wrong interpretation that it is simply about the alteration of the thought process. Delgado [In 1893 Emil Régis coined the eponym Cotard's syndrome, which was later popularized by Jules Séglas , 6. Did  Delgado  also reaIn order to briefly examine some characteristics of Cotard's syndrome, we present the case of a patient with schizophrenia who concurrently developed this syndrome. We describe the clinical course and response to treatment.It is about a 50-year-old male patient, native of Cajamarca, who had completed high school and lived with his son and daughter-in-law for three months. His family psychiatric background included a mother with bipolar affective disorder, a father who was a heavy drinker, and two sisters with depression diagnoses. None of them had presented Cotard's features in the course of their disorders.Since the age of 13 the patient has presented behavioral changes, with marked isolation due to fearing other people and poor school performance so he repeated third year of high school. The patient completed his studies with difficulties and had no interest in continuing, so he decided to work on his parent's farm. His relatives described him as “strange,” “weird,” of “repressed character,” quiet, very dependent on his parents and as someone who took no initiative, ran no projects, did not bathe, and had no interest in personal hygiene. This behavior persisted and for periods got worse.At age 45 the patient was afraid to leave home, as he thought he would be killed., He said that the police wanted to take him for all the bad things he had done, and he hid in the field, and did not want to stay alone. His relatives sent him to a hospital in Lima, where he was first diagnosed with schizophrenia. He was treated with olanzapine 5 mg/day, but the intake was irregular.At age 49, the patient began to live alone in Cajamarca. He did not care about personal hygiene nor basic needs; he began giving away his belongings. He persisted with the ideas of police persecution. At some point he said that it would be better to surrender and confess all the bad things he had done and also requested a priest to confess his “great sins.” He could not sleep for several nights and was very anxious. At a hospital in Chiclayo, he was treated with olanzapine 10 mg/day and clonazepam 2 mg/day; with this therapy, he showed some improvement, was no longer anxious, and could go off home alone.Three months before the admission to our unit, the patient moved to Lima with his son and started working in the cleaning area of a school. He had however a hard time adapting. He stopped taking olanzapine and clonazepam after fifteen days of treatment. He began to say that he was guilty for all the bad things he had done, as being unfaithful and attempting to rape his niece and sister-in-law. He felt scared and thought his relatives would report him and that he would go to jail.Twenty days before admission to our unit, the patient refused to eat; he said the food was rotten as he was. Again, he was anxious, asked his relatives for help, and said there were people who wanted to kill him. He heard loud noises and began to see others' faces blurred, saying that it was because they were all dead and also said that he was dying because he was not in the “glory of Lord.” For all of these, he was taken to a psychiatric hospital in Lima, where he is treated with fluoxetine 10 mg/day and quetiapine 50 mg/day. He showed no improvement with this therapy.Seven days before admission to our unit, the patient mentioned that he was already dead, his stomach did not work, his liver was decomposed, his brain was paralyzed, and his face lacked blood. He did not eat for fear of dying. The sounds got defined features, becoming imperative voices telling him “to leave this world, he was the devil.” Negativism emphasized, he did not eat, and his body weight diminished 4 kg. He stayed motionless in his bed most of the day and decreased his communication. He expressed his desire of dying to end all his suffering.Four days before admission to our unit, the patient's relatives took him to a psychiatric hospital due to persistence of symptoms. He was again diagnosed with schizophrenia and admission was indicated.The patient remained hospitalized for three days. During this time he received haloperidol 30 mg/day IM and clonazepam 3 mg/day. Since he did not show any improvement, his family decided to bring him to the emergency room of our hospital, before being admitted to the service of General Psychiatry.On physical examination scaly lesions on the scalp were found, generalized rigidity, and short step gait. The rest of the somatic examination did not reveal any pathological findings. During mental examination, the patient was found in a pharaonic position, with narrow consciousness, confusion, paralysis of self, derealization, and depersonalization. He had an altered consciousness of existence and execution; his attention was easily fatigued; he had feelings of strangeness with goal frustration, imperative auditory hallucinations, visual illusions, and cenesthopathic delusions. He displayed precategorical thinking such as mental concretism, delusions of nonexistence, immortality, and condemnation. The speech was characterized by poverty and hypophonia. There was also flat affection, paranoid mood, ambivalence, and feelings of guilt. Finally, the patient displayed decreased vital energy, insomnia, hypokinesia, and waxy flexibility, maintaining persistent positions as well as lack of spontaneity.μg/ml. Upper endoscopy showed esophagitis Los Angeles A. On brain computerized tomography (CT) scan no alterations were found.In lab tests, alterations were found in vitamin B12:190  pg/mL and Dimer-D: 1.45  The next diagnoses were proposed: (a) schizophrenia (295.90), (b) gastroesophageal reflux disease and esophagitis, and (c) seborrheic dermatitis. It was decided to start treatment with aripiprazole 30 mg/day and clonazepam 2 mg/day. The patient was significantly improved after two weeks of treatment. Delusions were diminished and emotional resonance improved.Berrios and Luque , when hiThis syndrome is considered to be rare. Ramirez-Bermudez et al.  reportedAccording to Coltheart et al. , Cotard'(a) Delusions of negation are the most representative symptom of Cotard's syndrome. Negation may affect the somatic constitution of the patient; the metaphysical representations were created on their own as what has happened with our patient. It differs from persecutory delusions, where patients are great ontologists, creating rich worlds and new metaphysical identities . In othe(b) Delusions of immortality: we noticed that our patient mentioned he was dead but was afraid of dying. This situation, apparently paradoxical, was described as a form of delusion of immortality in the original works of Cotard  and Ségl(c) Delusions of condemnation were shown as constant self-accusations in our patient. Everything that happened was a form of divine punishment to atone his “great sins.” Of interest is also the content of verbal hallucinations, according to which our patient was the devil himself. For Séglas , the del(d) Disturbed sensation is considered as one of the most important phenomena in psychopathology due to its role in the development of delusions. Analgesia, hyperalgesia, and paralgesia are found. In addition, disturbances in visceral sensation may be present; for instance, our patient reported generalized malaise related to anatomical and functional conditions of his internal organs (“his liver was rotten”), the delusive perception of a persistent gastric problem, which he said led to his death, and had its origin in gastroesophageal reflux disease. With regard to the circulatory and nervous systems , we did not find any disturbance that could explain these delusive perceptions. In addition, there are several situations concerning organ perception; for example, Séglas  reported(e) Many of the following phenomena were found in our patient: mutism with modifications of language, food refusal, suicidal ideation and suicide, or voluntary mutilation .The theoretical explanations to the delusions in this syndrome vary  and can μg/ml) without any organic cause. As already reported on a catatonic syndrome [μg/ml) may be suggestive of a catatonic diagnosis.Apart from the delusional ideas we found catatonic symptoms in our patient. This combination is very rare and has been reported in only a few cases –26. It isyndrome , some auTreatment for Cotard's syndrome focuses on its clinical origin. Thus, antidepressants can be useful in patients with affective disorders , and theMonotherapy treatment with sulpiride 300 mg/day was reported as successful in a 33-year-old patient with schizophrenia who developed the Cotard's syndrome, and Shiraishi et al.  concludeRegarding the psychotherapeutic treatment of Cotard's syndrome, there are few reported cases since most reports focus on pharmacotherapy. Bott et al.  reportedCotard's syndrome is a rarity in psychiatry. The psychopathology exceeds by far the unique association with the nihilistic delusions that have been emphasized the last years; we can also find delusions of immortality, enormity, guilt, possession, and persecution, with psychopathological alterations of affection and will. Regarding treatment, the combination of antipsychotics and antidepressants is often used, but if this shows no improvement, ECT is suggested.


Ambiguous images such as Rubin’s vase-face can be interpreted in at least two different ways. These interpretations are typically taken to be mutually exclusive, and ambiguous images have thus served as models of perceptual competition. Here, we present data that challenges this view. In an online survey, we found that a large proportion of people within the general population reported that the two percepts were not competing but could be perceived simultaneously. Of those who reported that they could see both percepts simultaneously, we invited 17 participants to take part in a functional magnetic resonance imaging (fMRI) experiment. In the scanner, participants saw images that could be interpreted as either a landscape or a face and reported at every point in time whether they perceived predominantly the face, the landscape, or both simultaneously. We explored behavioral and neurophysiological (with fMRI) correlates of the reported subjective experience of entertaining two percepts simultaneously by comparing them to those of the simple percepts . First, by comparing percept durations, we found that the simultaneous state was as stable as the two other percepts. Second, by measuring blood-oxygen-level-dependent (BOLD) signal levels within the fusiform face area (FFA), occipital face area (OFA) and parahippocampal place area (PPA), we found evidence from objective data that confirmed the subjective reports. While the results in FFA and OFA were not conclusive, in PPA, BOLD signal levels during subjective reports of perceiving both a landscape and a face were lower than the BOLD signal levels associated with reports of perceiving a landscape . In sum, the objective measures suggest that entertaining two percepts simultaneously in mind can be regarded as a distinct (mixed) perceptual state. We argue with these results that a more central role of subjective report in cognitive neuroscience is sometimes warranted. In his book “Sampling Inner Experience in Disturbed Affect” Hurlburt  reported“… I then sketched Rubin’s well-known ambiguous figure of the two faces/vase. What do you see? I see two faces in profile, and a candlestick or vase or something in the middle. Do you see them both at the same time, or alternating, the faces and then the vase and then the faces, etc.? I see them both at the same time. Try to see the faces. Can you do that? Yes, but the vase is there also. […] I then turned my notepad, on which I had sketched the ambiguous figure for Fran, back towards me so that I could record my observations. The unintended result of this was that the faces/vase drawing was now turned obliquely on its side when Fran viewed it. “Oh”, she said, “now I see what you meant! It’s alternating now”, which meant that she experienced herself as focusing first on the faces, then on the vase, etc. After that, she could easily comprehend my questions about change of focus. …”This intriguing report contrasts with the widespread notion that the two percepts in a bistable image are strictly alternating and instead suggests that they can in principle be superimposed in mental space and time.Some previous work has considered situations in which two percepts coexist. A prime example of this situation is the phenomenon of traveling waves in binocular rivalry  should in turn not be followed more often than chance by the other percept .We selected participants that reported to be able to see two percepts simultaneously in an online survey, and asked them to continuously report their subjective experience, while seeing a bistable image. Our assumption was that the phenomenological differences between the alleged perceptual states should manifest in objective measures of behavior and brain activity. Concretely, we assumed that if the simultaneous percept is a distinct stable percept and not just an unstable transient state, its reported duration would be comparable to that of the two main percepts. Instead, if the simultaneous percept were better described as a transitional state, its reported durations would be much shorter than the two main percepts. Further, some studies have shown individual stability in percept duration , suggesting that this could be considered an individual trait , BOLD signal levels in FFA, OFA and PPA would be distinct for the simultaneous percept as compared to the two main ones.Further, we sought to characterize brain activity during the simultaneous perceptual state. We hypothesized that BOLD signal levels in FFA, OFA and PPA would be consistent with subjective reports. Concretely, we expected higher activity in FFA and OFA while participants reported seeing the We first conducted a short online survey with the double aim of: (a) obtaining statistics from a large sample from the population; and (b) identifying potential study participants who reported to be able to see two percepts simultaneously in an ambiguous image. In the survey, we explained that when seeing ambiguous figures, some people have a preference for seeing one or the other percept, and others have no preference at all. As a cover story, and to avoid biasing responses, we simply stated that we were interested in which “perceptual type” each person was. We did not mention in the survey that we would invite participants based on their responses. In the survey, participants saw six bistable images, and answered two questions for each image. The first question asked directly about the preferred percept. Possible answers were “I see the two figures alternating”; “I see the two figures mostly alternating”; “I see the two figures mostly simultaneously” and “I see the two figures simultaneously”. We also included the alternative “I see only one figure” for cases in which participants could not identify the two alternative interpretations. The second question asked about perceptual effort. Possible answers were: “It is easier for me to see the two figures alternating”; “It is mostly easier to see the two figures alternating”; “It is mostly easier to see the two figures simultaneously” and “It is easier for me to see the two figures simultaneously”. Again, we included the alternative “I see only one figure”.mean ± SD: 23 ± 5 years) in this screening stage. The majority of women that responded to our survey mirrors the majority of women registered as Psychology students in the Universities where we distributed the link. We invited only those participants that scored at least 7 out of 12 points to participate in the experiment . Seventeen healthy participants accepted to take part . All participants were right handed and had no recent history of psychiatric or neurological disease. This study was carried out in accordance with the recommendations of Ethics committee of the German Psychological Society (DGPs) with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki.We distributed a link to the screening survey through the mailing lists of Psychology students of two German universities. We received 282 responses  in which the alternating percepts corresponded to faces and landscapes , we compared BOLD signal between all three reported percepts, for each participant and irrespective of the image presented. Because the percept dominance was determined by each participant and not experimentally, we could not ensure an even distribution of all three perceptual durations for each image. Thus, and to prevent any systematic errors due to biases by the low-level properties of any particular image that could have dominated any specific percept, we matched the contrast and luminosity of all rivalry images with the SHINE toolbox  using a 12-channel radiofrequency head coil.We collected structural images using a three-dimensional T1-weighted magnetization prepared gradient-echo sequence (MPRAGE) based on the ADNI protocolWe collected functional images using a T2*-weighted echo planar imaging (EPI) sequence sensitive to BOLD contrast .To localize FFA, OFA and PPA in each participant, we did two localizer scanning runs. In each run we presented eight series of 12 images. Each series of images contained either neutral faces , and held down both keys if they saw the two percepts simultaneously. One or both of the words (“FACE” and/or “LAND”) were highlighted while participants held down the corresponding keys to provide feedback for their responses. We asked participants to avoid focusing on only one of the percepts, and instead to balance the total amount of time across all three percepts. Importantly, we also instructed participants to report as faithfully as possible the percept that they really perceived in that very moment. To increase the rivalrous aspect of the images, we split the 90-s presentation time into two 45-s periods. During the first 2 s of each of these periods, we presented two attentional cues. These cues could not be taken as emphasizing either the face or the landscape interpretation of the image. Instead, as the example in Figure landscape viewing and the eye region for face viewing). We asked participants to focus on these regions, and try to interpret them as any one of three options: exclusively part of the face, exclusively part of the landscape, or as part of both simultaneously. Importantly, the attentional instruction cue was only displayed for 2 s and disappeared afterwards to avoid obstructing the images. Participants were asked to continue focussing on the cued feature of the image even after the attentional cue had disappeared.In total, we presented 14 different bistable images . In the localizer runs, we modeled each stimulus presentation as a discrete event, with a fixed duration given by the duration of each image. In the multi-stable perception task, we modeled each self-reported percept event  as a discrete event, with a duration given by the total trial duration. The resulting vectors were convolved with a canonical hemodynamic response function (HRF) and its temporal derivatives to form the regressors in a design matrix. We used a high-pass filter of 128 s to remove low-frequency drifts in the time series data. We also included in the GLM realignment parameters in all 6 dimensions to account for variance associated with head motion. Statistical parameter estimates were computed separately for each voxel for all columns in the design matrix at the within-participant level.faces > landscapes, for FFA and OFA, and landscapes > faces for PPA), thresholded at p < 0.001 (uncorrected). Finally, we used the Marsbar toolbox (version 0.43We followed the Group-Constrained Subject-Specific (GSS) approach . Multiple sources of variability have been related to individual differences in the properties of bistable perception. Albeit in a different paradigm of gender perception in point-like walkers, Schouten et al. , so we did not consider participants’ gender when selectively inviting them for the fMRI study.Figure n et al.  reportedTaken at face value, these results show that an important part of the student population that we surveyed reported to be able to entertain two percepts simultaneously, especially in the case of those images that we included in the “Figure-ground” and in the “Global vs. Local” categories. This was less strongly so when the alternation between the two percepts required a complete reinterpretation of the image.The results of this short online survey do not provide any details about the phenomenology of the simultaneous percept so, to better understand this alleged simultaneous perceptual state, we measured BOLD signal activity in a selected sample of participants while they viewed ambiguous images. In line with the survey results, the ambiguous images that we selected as stimuli depicted one stimulus (a face) when processed globally and a different stimulus (a landscape) when processed locally.face, landscape, or simultaneous). We first considered the behavioral durations of each percept.In the fMRI scanner, participants reported continuously which was the dominant percept  than only the landscape  or only the face  in the pictures. These differences were not statistically significant ;  = 1.38, p = 0.262, partialη2 = 0.08, Greenhouse-Geisser corrected). We also examined the number of occurrences of each percept. Here, participants showed more occurrences of the simultaneous percept  than only the landscape  or the face percepts . A one-way ANOVA revealed that the differences were statistically significant  = 16.63, p < 0.001, partialη2 = 0.51). Follow-up t-tests revealed that this difference was driven by the greater number of occurrences of the simultaneous percept (simultaneous vs. landscape: t(16) = 4.49, p < 0.001, d = 1.09; simultaneous vs. face: t(16) = 5.20, p < 0.001, d = 1.26), but not between the face and landscape percepts (t(16) = 0.68, p = 0.51, d = 0.16).Because percept durations have often shown to be stable and trait-like . We found that the proportion was slightly but reliably above chance level  = 3.415, p = 0.004, d = 0.828). We note however that very short percept durations  were relatively overrepresented in the data  = −0.551, p = 0.589, d = −0.134). This suggests that while short simultaneous percepts were often transitional, this was not necessarily the case for the longer-lasting simultaneous percepts.We then asked if simultaneous percepts are merely transitional. Concretely, we calculated for each participant the proportion of a Figure . We therface and landscape conditions  but we found no evidence for a correlation between the simultaneous and face  or simultaneous and landscape conditions . Further, we did a Fisher r-to-z transformation to statistically test the differences in correlations. We found that the correlation between the mean face and landscape durations differed significantly from both the correlation between face and simultaneous conditions,  and from the correlation between the landscape and simultaneous conditions .When examining the relationship between the percept durations with a Pearson correlation test, there was a clear correlation between the face, landscape and simultaneous) for each of the three ROIs.Finally, we quantified BOLD signal levels in FFA, OFA and PPA, areas known to show selectively stronger BOLD activity with attention to faces or landscapes. We extracted the BOLD signal in each condition relative to baseline in the three ROIs. Figure face and landscape conditions. We ran our statistical analyses on the mean percent signal change over a window of 4–6 s as a summary measure  = 3.148, p = 0.008, d = 0.872). This suggests that participants were able to accurately identify and report their subjective perceptual state. Turning to our main condition of interest, we examined the BOLD signal level for the simultaneous condition. We found that it was significantly lower than for landscape (t(12) = −2.511, p = 0.027, d = −0.696) though not different than the face condition (t(12) = 1.554, p = 0.146, d = 0.431).In a planned comparison and as a positive control, we first examined BOLD signal levels in PPA and FFA associated with the e Figure . The PPAface percept to show the strongest levels of BOLD signal in these face-selective regions. Instead, we found no differences between face and landscape conditions (with t(12) = −1.884, p = 0.084, d = −0.523 for FFA and t(12) = −1.626, p = 0.130, d = −0.451 for OFA). When we compared BOLD signal for simultaneous and face percepts in these regions, we found no differences relative to the face condition (FFA: t(12) = −1.169, p = 0.265, d = −0.324; OFA: t(12) = −1.686, p = 0.118, d = −0.467); but significant differences between the simultaneous and landscape conditions (FFA: t(12) = −4.522, p < 0.001, d = −1.254; OFA: t(12) = −2.898, p = 0.013, d = −0.804).FFA and OFA, instead, did not show the expected pattern. We expected the simultaneously entertain the two percepts; rather than experiencing them in alternation. To better understand these phenomenological reports, we explored the objective correlates of the alleged subjective state. In a group of selected participants we explored the behavioral and physiological bases for the reported simultaneous perceptual state, and compared them to those of the single percepts. As a way to track the brain activity associated with the perception of—and attention to—each of the two percepts, we used bistable images that included a face and a landscape, which were expected to elicit stronger BOLD signals levels in FFA and OFA, and in PPA respectively. In an fMRI task, we asked participants to view these bistable images, and to continuously report their perceptual state. We defined three conditions , based on each participant’s subjective report.The different possible interpretations of ambiguous images are typically taken to be mutually exclusive, as it is assumed that the multiple percepts compete for conscious access. In our survey and the present experiment, we showed that this might not always be the case. In an initial population screening we found that, when prompted, a large proportion of the population (39% of men and 41% of women) reported that they were able —and sometimes found it easier—to simultaneous condition from the other two, supporting the phenomenological reports, which identify it as a distinct perceptual state. We use the fMRI data as objective evidence to back the subjective and phenomenological claims.We sought to identify any potential objective measures that would distinguish the simultaneous percept is at least as stable as the face and landscape percepts, suggesting that it is not just a transitional, short-lived perceptual state. And, while short-lasting reports of the simultaneous percept were more often than chance flanked by two different percepts , this was not the case for the longer-lasting reports of the simultaneous percept. This suggests that the simultaneous state is not necessarily the transition between the other two “simple” percepts. Further, we examined the correlations between the mean duration of each percept, for each participant : BOLD signal levels for face reports were no different than those for landscape. According to our participants’ subjective reports, we explain this result ad hoc: at debriefing all participants spontaneously reported that the faces depicted in the images were very difficult to ignore. Admittedly however, this is a speculation that we cannot support with behavioral data, because we found no evidence to suggest that face percepts occurred more often or lasted longer than landscape percepts. However, we argue that subjective reports are to be trusted, including those at debriefing. Hence, taken together, the subjective reports during the task, at debriefing and the behavioral results during the task suggest that participants may have found it more effortful to attend to the landscape only and completely ignore or suppress the face percept. As a consequence, they might have been only partly successful at doing so. Thus, periods during which landscape percepts were reported could have also included perceived faces. In line with this suggestion, faces are more quickly and more accurately recognized than landscapes or houses, even when presented upside down Diamond and Carey (The levels of activity in FFA and OFA across conditions, on the other hand, were not informative. BOLD signal in these two ROIs did not vary as expected with the reported control conditions (nd Carey . This isnd Carey  and facend Carey . Especiand Carey . This coboth a face and a landscape. No participant spontaneously reported any piecemeal perception as it has been described in, for example, traveling waves of piecemeal perception in binocular rivalry paradigms. We thus take the strong view that the phenomenology that we describe here is different from that reported before in mixed states. Admittedly however, stronger evidence for this view could only come from specifically probing participants to describe the differences between the two ways of simultaneous perception.We argue that the simultaneous state allegedly experienced by our participants is phenomenologically and physiological different from the mixed states or piecemeal perception typically observed in many cases of bistable perception (Knapen et al., The online survey that we first conducted revealed that there is natural variability within the normal population on the properties of bistable perception. This observation goes in line with the literature highlighting differences between individuals in the dynamics of bistability. Inter-individual differences have been related to molecular, structural and functional factors (for reviews see Kleinschmidt et al., Given the multiple levels at which differences in brain structure and function can be translated into overt differences in the properties of bistable perception, it is possible that the ability to entertain two percepts simultaneously is related to measurable properties of brain structure. With this study we highlight the possibility that the perception of simultaneous states might serve as an additional parameter of interest in the understanding of bistable perception.It has been argued that introspection cannot be trusted as a reliable source of information: subjective report can be incomplete and inaccurate (Nisbett and Wilson, simultaneous percept from a quick alternation between the two single percepts. In other words, it is in principle possible that what participants perceive to be the coexistence of two percepts was in fact a very rapid alternation between two single percepts. When asked this question explicitly, our participants consistently maintained that the term “simultaneous” was a more accurate description of their subjective experience. Conducting interviews with participants trained in describing their pristine experience (Hurlburt and Heavey, We should point to several important limitations of these data. Perhaps the strongest limitation is that they do not suffice to distinguish a true Our data are specific in two important ways that limit their generalizability. First, we tested only one kind of bistable stimuli where the two percepts resulted from either local or global processing. We selected these stimuli because they contained faces and landscapes as alternating percepts, both of which have known brain correlates. These stimuli would then allow us to identify objective correlates of the subjectively reported percepts, thus validating the subjective report. Importantly however, these stimuli are not representative of all kinds of bistable perception (as discussed further above, see Hasson et al., simultaneous and the alternative “simple” percepts. It is possible that a different sample of participants for whom entertaining two percepts simultaneously is possible but difficult would have revealed a qualitatively different pattern of the duration subjective reports. Thus, these results could be extended in interesting ways by including a comparison to a control group to explore, for example, whether there are any differences in brain structure that could account for this difference in the available perceptual states.Second, because in this study we were specifically interested in studying the simultaneous percept, we investigated their behavioral and brain correlates only in participants that reported to experience it and did not include a “control group” of participants that did not experience the simultaneous percept. While this comparison would not have been informative in understanding the nature of simultaneous percept alone, it could have informed the interpretation of the fMRI results. As we described above, several studies have reported inter-individual differences in perceptual exclusivity. Hence, it is in principle possible that the putative automatic face processing and accompanying enhanced BOLD activation in the face-selective areas FFA and OFA was not a consequence of the stimulus material but an idiosyncrasy of this preselected subgroup. Finally, our sample of participants, explicitly selected for high levels of simultaneous perception, reported similar durations of the EF, MB, YW and SK designed the experiment; wrote the article. MB and YW did the online survey. EF programmed the experimental task. EF, MB and YW collected the data; analyzed the data.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Statistical Bulletin of the Metropolitan Life Insurance Company concluded, as a final remark, that: “The important lesson taught… is that there is an optimum build with reference to mortality. The average build is not the best build. Those who weigh between 10 and 20 % below average show the optimum condition of longevity at most of the ages after early adult life” [Almost a hundred years ago, back in 1922, when undernutrition was a larger concern than obesity, the authors of the These initial observations in life insurance data, showing that individuals with a normal body weight lived longer than overweight clients, have during the last decade been followed by numerous epidemiological studies on body mass index (BMI) and mortality. The message, that obesity is hazardous to health, initially fell on deaf ears. Today, however, when overweight is more common than underweight, even in low- and middle-income countries, the same message has impacted public perceptions to such a degree that we are bombarded with headlines including expressions like “obesity epidemic”. Meanwhile, research and epidemiologists have moved on. We are now not only studying obesity and adult mortality, but obesity in one generation and mortality of the next.European Journal of Epidemiology, the results of two complementary investigations shed light on a potential window of opportunity for lifestyle intervention—pregnancy. Morales-Suárez-Varela et al. [In this issue of the a et al.  primarila et al.  conductePre-pregnancy overweight and obesity have repeatedly been shown to increase the risk of complications during pregnancy. A meta-analysis including more than 10,000 fetal deaths, revealed that for each 5-unit increase in maternal BMI, the summary adjusted relative risk for fetal death increased with 21 % . FurtherPhysical activity is a modifiable factor that can prevent premature mortality in the general population, but that has not been convincingly documented to be associated with fetal death. This may in part be due to the fact that registers set up for health care commonly do not include behavioral factors such as physical activity, and thus, register-based studies lack this information. Morales-Suárez-Varela et al. solved this issue by putting an astonishing amount of work into conducting telephone interviews with the 87,930 pregnant women in the cohort.Overall, in the study by Morales-Suárez-Varela et al., smoking during pregnancy was associated with a higher hazard ratio (HR) for fetal death if both parents smoked compared to non-smoking parents; HR 1.22 (95 % CI 1.02–1.46). There was also evidence of an additive interaction between smoking and high BMI, suggesting that smoking may increase the negative effect of a high BMI on fetal death. No interaction was observed between smoking and exercise.Despite the impressive effort to assess both exposure and confounders by conducting telephone interviews in this large study, the authors may regret that physical activity was rudimentary assessed with the question: “Do you get any kind of exercise during pregnancy?”. Implicit in epidemiological research is the ability to estimate the strength of an association between exposure and outcome with as little error as possible. Accurate measurement is therefore central. Physical activity is complex to measure as it is a behavior that can take many forms. Exercise is only one type of physical activity behavior and activities in different domains or of different intensities may have different effects.Aune et al. , who conGestational diabetes, i.e. glucose intolerance discovered for the first time during pregnancy, is one of the most common pregnancy complications. It is associated with a number of adverse health outcomes for both the mother and the offspring. Results from previous studies have been conflicting, some suggesting no association and some suggesting that a higher level of physical activity is associated with a lower risk of gestational diabetes. The strengths of associations have spanned a wide range and decreased risks between 10 and 90 % have been shown. Three previous meta-analyses on the topic –8 came tPregnancy is no longer a contraindication for physical activity, but is rather recognized as a window of opportunity for behavior modification. It is safe to continue or start most types of exercise, according to the American College of Obstetricians and Gynecologists (ACOG) which encourages pregnant women with uncomplicated pregnancies to undertake regular physical activity during pregnancy . UnfortuWomen’s and children’s health have undergone immense improvements during the last generation. Nevertheless, the century old advice, to weigh below average, still holds true. The worldwide prevalence of obesity has doubled since 1980 and is not only a high-income country concern, according to WHO . Globall


Many important and rapidly emerging pathogens of humans, livestock and wildlife are ‘vector-borne’. However, the term ‘vector’ has been applied to diverse agents in a broad range of epidemiological systems. In this perspective, we briefly review some common definitions, identify the strengths and weaknesses of each and consider the functional differences between vectors and other hosts from a range of ecological, evolutionary and public health perspectives. We then consider how the use of designations can afford insights into our understanding of epidemiological and evolutionary processes that are not otherwise apparent. We conclude that from a medical and veterinary perspective, a combination of the ‘haematophagous arthropod’ and ‘mobility’ definitions is most useful because it offers important insights into contact structure and control and emphasizes the opportunities for pathogen shifts among taxonomically similar species with similar feeding modes and internal environments. From a population dynamics and evolutionary perspective, we suggest that a combination of the ‘micropredator’ and ‘sequential’ definition is most appropriate because it captures the key aspects of transmission biology and fitness consequences for the pathogen and vector itself. However, we explicitly recognize that the value of a definition always depends on the research question under study.This article is part of the themed issue ‘Opening the black box: re-examining the ecology and evolution of parasite transmission’. This insyringes  and papesyringes . Althoug humans'  , where definitive and intermediate host fitnesses are not directly affected by each other.One of the most obvious definitions is based on the recognition that most organisms we commonly recognize as being ‘vectors’ are hosts that transmit a pathogen while feeding non-lethally upon the internal fluids of another host. Largely this definition overlaps with the  & Kuris , p. 509,haematophagous arthropod definition (definition #4), which defines vectors only as blood-feeding arthropods such as mosquitoes, ticks, sandflies, tsetse flies and biting midges [Rhipicephalus microplus). This definition is used explicitly by several groups including the European Centre for Disease Prevention and Control [Varroa mites). In addition, other large groups of vertebrates, such as rodents, which also spread pathogens through their saliva , and that are often considered vectors, are also excluded.A related definition is the g midges . Such ar Control  and the  Control , and oth Control ,29 or ex Control . A weaknmorbidity-based definition (definition #5) describes a vector as a host within a multi-host transmission cycle for which infection does not significantly reduce that host's fitness. However, while fitness effects of the pathogen on organisms universally accepted as vectors are often not overt, they have been frequently observed experimentally: for example, effects on fecundity [mobility-based definition (definition #6) defines vectors as the most mobile host in a transmission cycle of two or more hosts. This definition frames the distinction in terms of parameters likely to have consequences for epidemiology , offers the advantage of simplicity and fits most disease systems traditionally considered to be vector-borne. However, under this definition, ticks would not be defined as vectors because they are typically less motile than their host. In addition, ‘vector’ identification using this definition may be difficult in practice; for example, insect vectors may occasionally be blown very long distances under certain atmospheric conditions [An alternative perspective for defining vectors is one that emphasizes some functional aspect of the vector's life history, or that of its interaction with the pathogen. For example, the ecundity , feedingecundity  or feediecundity . Alternanditions  but theia. Clearly, each definition emphasizes different aspects of vector–pathogen-definitive host biology, but there may also be substantial overlaps between them. When, then, is ‘vector’ a useful definition, and under what contexts are different definitions applicable? In what follows, we consider from a variety of perspectives which definitions are most useful, and the key aspects of host–vector–pathogen biology that need to be captured within any meaningful definition of ‘vector’.Some differences in applicability between each of these definitions are illustrated in figure 13.A vector could be considered just another host in a parasite's life cycle, and applying some of the above definitions to multi-host systems can result in the classification of two or more different groups as ‘vectors', implying that it is appropriate to use similar ways to represent them in mathematical models . Here, (a)R0). R0 is the expected number of new infections generated by a single infected individual in a wholly susceptible host population (or multi-host community), and so represents the potential for the pathogen to invade a naïve community, but also under some conditions it can be used to describe the contribution different hosts make to endemic persistence [R0 is given by an expression of the form :R0 is proportional to the sum of the reproduction ratios in hosts and putative vectors . Importantly, however, with a ‘true’ vector, pathogen transmission occurs through sequential, and repeated, feeding of the vector on the ‘other’ host species, which gives rise to an alternative R0 expression of the form:Multi-host–pathogen systems are often described theoretically within the framework of next-generation matrices ,37 or musistence  or pathosistence ; see §4b0R is characteristic of many theoretical models of vector-borne transmission [sequential; definition #7).Now the overall reproductive ratio is proportional to the product of the reproduction ratios in the host and putative vector. Equation (3.1) most closely captures the biology of ‘multi-host’ models, where pathogens have multiple potential transmission routes among hosts, i.e. there may be transmission between multiple host species, but infection of either can be independent of the other –41. A kesmission ,44, wherR0 relationship (equation (3.2)) would rule in many so-called ‘intermediate’ hosts (e.g. snails as hosts for schistosomes) as vectors, if they are an obligatory  host in the pathogen's life cycle. Because they play different roles in parasite life cycles, it seems appropriate that these different host types  should not necessarily be grouped under the same umbrella term. To separate those host types it may therefore be necessary to refine this definition, for example to include aspects of the ‘micropredator’ definition to emphasize the feeding component, and direct contact of the vector with the host, typical of the majority of considered vector species (c). In what follows, we consider additional/alternative aspects of vector–host–pathogen biology that may influence our definition of vectors.Importantly, this distinction arises purely from consideration of the population dynamics of pathogen transmission. As such, it overlooks other aspects of vector–host–pathogen biology that may be relevant in different contexts. For example, a definition purely based on the functional form of the  species c. In wha(b)Ixodes ricinus, which transmits B. burgdorferi and tick-borne encephalitis virus (TBEV) [Timescales are a critical consideration. If there are hosts that move, reproduce and die much more quickly than the other hosts in the system, then it may be useful to consider them separately from other hosts. A standard practice in simplifying complex models of host–parasite systems is to assume that short-lived life-history stages are at ‘quasi-equilibrium’ with the current population sizes of the longer-lived life-history stages . This res (TBEV) . These ts (TBEV) , and thes (TBEV) .B. burgdorferi and TBEV, in many ecosystems, one species of Ixodes tick acts as a nexus transferring infection between a large number of mammalian host species [Toxoplasma gondii infects a very wide variety of mammalian hosts, but continued transmission requires a felid definitive host [Where transmission between different host species funnels through one or a small number of species, then recognizing these differences via a special designation (whether ‘vectors’ or another term) may be helpful. In the case of  species . Here thive host .(c)In terms of classical approaches to modelling infectious diseases, a key component of many models of vector-borne infections is the assumption of frequency-dependent (FD) transmission, as distinct from density-dependent (DD) transmission. In the case of DD transmission, the rate at which an individual contacts other individuals depends on the density of infected individuals; as a consequence, as density increases, transmission rate will increase . On the The dynamics of transmission are very different for these two cases, and certain modes of transmission are more appropriately modelled as one or the other; for example, transmission via droplet or aerosol is density-dependent (high host densities result in more rapid spread), whereas the rate of infective contact via sexual transmission is not. It may be possible to predict the nature of the transmission function for a known system with a reasonable understanding of the biology of the organisms involved ; for exaB. burgdorferi is not is unlikely to satisfy most people. The relationship between population density and transmission is therefore likely to be acceptable as a qualification for defining a vector only in combination with other traits.Clearly, from the perspective of a mathematical epidemiologist, it is not particularly helpful to have a definition of vector that encompasses hosts which exhibit both density- and frequency-dependent rates of potentially infectious contact, because they must be represented differently within modelling frameworks. Furthermore, a definition of ‘vector’ that suggests that HIV is vector-borne but A perhaps more basic problem with using this definition is that it assumes that contact rate functions can be strictly classified as one or the other. In practice, many attempts to characterize natural populations within this paradigm have found results intermediate between these two extremes, and it may be more helpful to think of this distinction as a spectrum rather than a dichotomy . Hence, (d)Bacillus thuringiensis). At the same time, overly broad definitions will not be helpful; most strategies effective at interrupting the spread of malaria or dengue will not be applicable to the control of schistosomiasis or rabies.Defining a class of hosts as a ‘vector’ or otherwise differentiating them on certain criteria may help in predicting patterns of spread or the likely effectiveness of certain control strategies. Here, the ecological definitions (particularly the ‘haematophagous arthropod’ definition 4) are most likely to be useful, as many groups of haematophagous arthropods share characteristics with clear consequences for epidemiology or control, including ectothermy , a relatively short lifespan and high intrinsic rate of reproduction . They may also possess ecological and metabolic similarities such as aquatic juvenile stages , flight, or vulnerability to similar control products such as certain chemicals (e.g. neonicotinoids) or bacteria (e.g. (e)Histomonas meleagridis, is transferred to the egg of the caecal nematode Heterakis gallinae, and passed onwards to birds by the ingestion and subsequent hatching of larvated worm eggs [Heterakis and in that way transfer Histomonas [Wolbachia endo-bacteria in filarial nematodes, for example, appear to be responsible for aspects of filarial disease [Fasciola hepatica modulates host immunity and increases the establishment and persistence of bacteria such as Salmonella [Bordetella [Leaving definitions aside, vector-borne disease theory might be usefully applied to hosts or objects not usually considered as such. Parasitic helminths are responsible for transmitting several economically important pathogens in plants . The strorm eggs . Whereasstomonas , the rol disease , whereaslmonella  and Bordrdetella .Salmonella bacteria were found to survive adverse environmental conditions better when within the free-living nematode Caenorhabditis elegans [A combined micro- and macro-parasite modelling framework has been used to investigate the potential vectoring of bacteria by parasitic nematodes . Results elegans . This in elegans , this raThe study of vector-borne disease has provided theoretical frameworks and insights that can be applied usefully to other systems. Hypodermic needles, for example, might be considered as vectors under definition #1, and pseudo-biological characteristics defined, such as rates of birth (entry of new needles into the population), infection (contamination) and death , whereas the use and reuse of needles is analogous to biting rate. This thought model has been applied to the problem of HIV transmission and supported needle exchange as part of harm reduction approaches to disease control . Thus, d4.(a)R0, of the pathogen. Although primarily an ecological measure of the pathogen's ability to invade a naive host community, it can also be used in an evolutionary context as an operational definition of pathogen fitness [R0, such as those presented above, one can ask how changing a pathogen trait of interest alters R0; hence, one can predict the evolutionary trajectories of those traits under different selection scenarios and trade-offs. In particular, from an evolutionary perspective we suggest that it is important to recognize that the key defining feature of vector transmission is that every pathogen generation (i.e. passing from one infected host to another infected host) involves contact with the vector [0R expressions of the same functional form (e.g. equation (3.2)), they would have very different evolutionary dynamics; this further emphasizes the need to differentiate vectors and intermediate hosts.As described above, theoretical studies of multi-host systems often seek to characterize the functional form of different host species’ contributions to the basic reproduction number,  fitness ,65. Givee vector . As suche vector  A clear and relevant vector definition is potentially very helpful in offering insights into pathogen evolution, as it can illuminate key aspects of epidemiological systems that are critical for pathogen evolutionary processes. Despite this, many evolutionary and ecological models simplify or ignore much of the complexity of vectors. Like in the ecological models discussed in §4a, vectors are often treated as mobile syringes rather than organisms in their own right, and their broader ecology and behaviour are frequently subsumed into a black box described by their biting and mortality rates. Subsuming vector biology into a few vital rates of only the vector is analogous to subsuming or ignoring the mechanistic details of within-host dynamics, and only dealing with among-host processes  for studying pathogen evolution: in both cases, there is no opportunity for reciprocal feedback from the simplified level (within-hosts or within-vectors) to the between-host level . For vecAs an example, one pathogen trait for which interactions in the host and vector are likely to be influencing pathogen evolution is the production of transmission stages by malaria parasites. Because one infected red blood cell in a vertebrate host can produce multiple asexual parasites (capable only of infecting other red blood cells) or one transmissible parasite (required for infecting a mosquito vector), the proportion of infected cells that produce the transmissible stages is a ‘trait’ that is expressed in a host. Because, all else being equal, the more transmissible stages are produced in a given cohort of infected cells, the fewer red blood cell-destroying asexual parasites are produced, it is also a trait with clinical significance. A few theoretical studies have explored the evolution of this trait –75 but iIntuition might suggest that a trait like the production of transmissible stages would influence transmission to vectors and performance in vectors, but for some other traits of interest it might not be so clear if interactions in the vector will modify or constrain evolution. Unexpected genetic correlations may invisibly influence the evolution of important pathogen traits. Malaria parasites, for example, are evolving resistance to current front line antimalarial drugs, and the putative mutations responsible appear to be in close proximity to a gene that is associated with evasion of mosquito immunity –80, lead(c)A high proportion of individuals within a population that are exposed to a potentially infectious dose of a pathogen may fail to develop a fully disseminated, transmissible dose under ‘typical’ infection conditions ,84. Simi5.b). However, from a population dynamics perspective, there is a clear mathematical difference between vector and non-vector multi-host systems: host species contribute either multiplicatively or additively to the pathogen's basic reproductive ratio. This suggests that the ‘sequential’ definition (#7) is most appropriate in this context, although that would also mean including intermediate hosts (e.g. snails for schistosome parasites) as vectors; hence a more appropriate population dynamics definition may be the intersection of the sequential (#7) and micropredator (#3) definitions (figure 1c). From an epidemiology and control perspective, it is important to clearly define what a vector is and why that is important before attempting activities such as vector incrimination. The criteria most used for this are those of Barnett [As we have seen above, and summarized in figure 1 Barnett , which aHaving a clear definition of a vector is also important from an evolutionary perspective. As we show above, the sequential feeding aspect of vector transmission is clearly a key point, resulting in different pathogen evolutionary dynamics from those seen under more general multi-host models . It is lMore generally, given the plurality of definitions in regular use, we suggest that authors writing about ‘vector-borne diseases’ give careful consideration to whether defining a vector within their system of interest is more likely to help or hinder understanding, and that wherever the term is used the authors clearly define it, and ideally justify the definition chosen. To paraphrase Box's  famous c


Precision medicine is a new and important topic in psychiatry. Psychiatry has not yet benefited from the advanced diagnostic and therapeutic technologies that form an integral part of other clinical specialties. Thus, the vision of precision medicine as applied to psychiatry – ‘precision psychiatry’ – promises to be even more transformative than in other fields of medicine, which have already lessened the translational gap.Herein, we describe ‘precision psychiatry’ and how its several implications promise to transform the psychiatric landscape. We pay particular attention to biomarkers and to how the development of new technologies now makes their discovery possible and timely. The adoption of the term ‘precision psychiatry’ will help propel the field, since the current term ‘precision medicine’, as applied to psychiatry, is impractical and does not appropriately distinguish the field. Naming the field ‘precision psychiatry’ will help establish a stronger, unique identity to what promises to be the most important area in psychiatry in years to come.In summary, we provide a wide-angle lens overview of what this new field is, suggest how to propel the field forward, and provide a vision of the near future, with ‘precision psychiatry’ representing a paradigm shift that promises to change the landscape of how psychiatry is currently conceived. Me. Me15]. .This is a very ambitious endeavour. However, the timing for successfully carrying out this task has never been more propitious. The odds of turning this ideal into reality have considerably increased with the development of powerful biological tools, methods, brain imaging and physiological techniques, as well as assessment of behaviours and life experiences, to characterise patients along with the advanced computational tools capable of analysing large datasets. The availability of massive information – ‘big data’ – provided by the acquisition of biological data on scale and by incorporating data from electronic devices such as smartphones is unprecedented, and is one of the multiple factors that now allows the analysis of diverse patient characteristics to be considered .Fig. 1Da defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions” [An interdisciplinary approach offers the potential to identify ‘biomarkers’ – “entions”  – as indentions” , 20, 21,Arguably, the most logical way of obtaining hypothesis-free and data-driven approaches in the neurobiology of psychiatric disorders is making use of ‘omics’ techniques. Genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics and lipidomics are capable of independently providing valuable information about the neurobiology of these psychiatric conditions. Further, when combined with a multi-omics approach, in what is called panomics, and analysed using system biology computations, they might unveil the underlying biological pathways involved in psychiatric disorders.Implications of systems understandings include the principles of redundancy, whereby multiple elements with overlapping functions are present for backup, of modularity, such that failure of one element does not lead to system-wide failure, and of structural stability, in which intrinsic mechanisms exist to enhance systemic stability. This implies that network-wide omics approaches are needed to capture the interactivity of these multiple overlapping elements . This nethe quality, condition, or fact of being exact and accurate” and “refinement in a measurement, calculation, or specification” [The noun ‘precision’ in the term precision psychiatry is, grammatically, a modifier to the word ‘psychiatry’. Its dictionary definition is “ication” . Thus, aAn analogy can be made using cardiology, a specialty far more advanced than psychiatry; 70 years ago tools to measure the un-observable aspects of heart structure and function were not available, now, these are taken for granted. Physicians would have endeavoured to personalise their assessments to each patient, yet they were not able to observe the heart’s behaviour or how it related to observable symptoms prior to the incorporation of measurements. The Framingham study, for example, spawned the assessment of standard vitals, along with a subsequent range of imaging techniques to determine whether the underlying biological problem is one of function (requiring perhaps a pacemaker or medication) or one of structure (requiring perhaps surgery). It would be routine to take serial images to provide a baseline from which to assess each individuals’ recovery and their subsequent risk for another acute problem. These measurements would also inform the importance of a personalised plan that considers the whole individual, from observables to non-observables, including lifestyle, diet and other techniques. The major challenge that precision psychiatry faces is that psychiatry does not yet use measurement to track the equivalent of vitals and images of the organs of interest, namely the brain and alterations in peripheral measures such as blood.the best way to predict the future is to create it” [A maxim of management is that “eate it” . By havieate it”  – will aeate it” . AlthougThe development of the field of precision psychiatry in its full totality is a gigantic but addressable enterprise that will most likely require synergy between academia, industry and government . Each ofAn entrepreneurial disposition is also needed for commercialisation of the developed technologies. This is a task suitable for a partnership of scientists with industry . FurtherFinally, all of the above steps will mean nothing if they are not applied. To apply precision psychiatry, clinical scientists will have to develop clinical guidelines specifying how the new developed technologies should be employed and clinically evaluated. This last step is crucial; since psychiatrists are not used to relying on instruments such as medical tests, the introduction of clinical guidelines, clearly informing how such new technologies should be employed and evaluated in clinical practice, will be necessary to guarantee the last translational step. Only when precision psychiatry is realised in ‘real life’ will it keep its promises –36.The ultimate goal of precision medicine as applied to psychiatry – ‘precision psychiatry’ – is to seek better lives for those suffering from mental illness. This will only be accomplished with the development of tools capable of providing better and more accurate diagnosis, of ascertaining prognosis, guiding treatment and predicting response to treatment, and aiding the development of new and better pharmacological and non-pharmacological treatments. If achieved and applied, ‘precision psychiatry’ will be of great consequence and will redesign the current landscape of mental illness.Art is I; Science is We”. Hopefully, the day will come when science is fully incorporated into psychiatry – a medical specialty deemed as highly subjective; then, we will collectively change from ‘I do’ to ‘We do’ and we will be practicing precision psychiatry. Paraphrasing Claude Bernard, whose goal in life was to establish the use of the scientific method in medicine, “Annotations: Rectangles indicate specific components; circles indicate domains; agglomerate of persons in grey indicates different individuals grouped together that, after precision psychiatry, will be better recognised. Bi-directional arrows, bi-directional relationships; uni-directional arrows, uni-directional relationships.