Desk Set? Besides showcasing the wit and chemistry of Katharine Hepburn and Spencer Tracy, its premise also predicted what has become a reality for many libraries throughout the country. The film takes place in 1957 at a television network’s reference library, which is supervised by Bunny Watson (Katharine Hepburn). The network decides to buy two computers: one for processing payroll and one for answering simple questions in the library. To ease the transition and to observe library functions, the network sends Richard Sumner (Spencer Tracy), the man who invented a computer named EMERAC , to the library. EMERAC sends the librarians into a frenzy because they are certain they will be replaced by this “electric brain” that only errs when “the human element” makes mistakes . However, the purpose of EMERAC is to liberate the librarians’ time for more important work, like research.Who can forget the movie At the end of the film, Bunny proves that “the human element” is just what makes their library successful when EMERAC gets overloaded trying to answer the rapid-fire ready-reference phone calls coming in from patrons and proudly declares to her staff, “Let’s show them what people can do!” Spoiler Alert: the librarians keep their jobs (which they thought were surely lost through a pink slip mix-up caused by the payroll EMERAC), and EMERAC proves helpful in basic tasks after all.The Library Staff Development Handbook by Mary Grace Flaherty is just the book to guide both the seasoned and newbie library supervisor alike.Sound familiar? Regardless if you have seen the film or not, you know the feeling of having to compete against the machines  that help us do our work. But, as Bunny points out to her fellow librarians, “no machine can do our jobs,” especially if we continually work toward improving and developing ourselves and our staff. The book opens with a preface that asserts, “An exceptional library of any time requires exceptional staff, individuals who are enthusiastic, engaged and willing to go the extra mile” (p. xi). The work gives readers different facets of staff development with practical examples, samples, tips, and real-life examples from various libraries. This book includes a table of contents, a list of figures and tables, an index, and a bibliography at the closing of each chapter.The first chapter introduces the reader to the idea that staff development is a continuous and ongoing process that creates a space for personalities to become interwoven into the institution or organization’s culture. To create a culture where fulfilled staff members thrive, the relationships that individuals have with their direct supervisors; the institutional rules, structures, and assets; and individual employees have to be considered. A first step is to look at how effective and inspirational the leaders are, and this chapter does an excellent job breaking down traits and giving useful anecdotes. This chapter contends that “the most important way a supervisor can empower staff is to cultivate an organizational atmosphere that values open communication, support and mutual respect. In practice, envision the ideal workplace and strive to be the supervisor whom you would like to have” (p. 4). Readers know that with technologies (like EMERAC) come the challenges of library staff being tasked to evolve and adapt, but this has been the case since the printing press. Flaherty claims, “When staff are content and fulfilled, it follows that work processes flow more smoothly and the workplace is more pleasant and productive” (p. 7).Desk Set, the staff was left out of the transition process when the “electronic brain” was introduced to and integrated into their workflow. In the second chapter, Flaherty lays out how to draft strategic, tactical, operational, and staffing plans and effectively communicate them to not just the organization, but also, as is the case with public libraries, to the community as well. The chapter provides resources to identify specific keys for strategic planning success, sample job descriptions, and tenure information with reading lists for additional information. The next chapter moves into the hiring and recruitment process, with clear-cut steps to recruit, interview, evaluate, and hire the best and the brightest. There is a helpful section on how to identify and target the different advertising outlets that are appropriate for the organization and an easy-to-use job advertisement format. There are also interview tips, rubrics for evaluating interviewees’ responses, and problem-solving skills.In Once soon-to-be exceptional staff members have been hired, how can they be guaranteed that the mechanical brain doesn’t replace them? Chapter four coaches leaders on the different types of motivation (extrinsic and intrinsic) and less positive interactions, including progressive discipline, appeals processes, and exit interviews. Flaherty explains that “staff who are positively engaged with their work and coworkers will likely be more positive, happy, and motivated and demonstrate a commitment to the workplace” (p. 46). She includes ideas about how to motivate staff, tools and methods for measuring staff engagement (and the key drivers fueling staff motivation), and how to keep staff happy. Examples she includes for keeping staff happy are focusing on individual staff members’ strengths and identifying their preference for work style, schedule, and so on. An easily forgotten tool to achieve workplace happiness is to remember to have fun while at work. Flaherty cites that “Individuals who report greater levels of workplace fun have significantly higher levels of job satisfaction, lower emotional exhaustion, and lower emotional dissonance” (p. 54).The next chapter interprets the term “staff development” to be a continuous, ongoing process that integrates into the overall functions and activities of the institution. Some examples are: education reimbursement, conference participation, allowance for self-directed activities, and ad-hoc workshops. She outlines steps for identifying and determining staff needs for development, such as administering surveys (an example template is provided). She follows with writing a continuing education policy  and looks at self-directing learning through online resources and mentoring opportunities. Chapter six explains in detail how to evaluate staff. She provides numerous and varied approaches to this normally stress-evoking process. This chapter focuses on the objectives-based performance review process, where there is staff interaction and engagement. I like this approach because the expectations are clear, performance is measurable, and staff goals can be linked to institutional goals. There are several helpful tools such as sample performance review forms, sample self-evaluations, sample performance, and a review appeals form.Desk Set who were ill-informed about the changes happening in their library, to be successful we need ongoing communication. To do our jobs successfully, we need to be partial owners of our institutions’ successes. As Flaherty put it, “If staff are aware of problems and any challenges the organization might be facing, they can be involved in identifying and enacting solutions” (p. 126). Communicating our inside perspective with our supervisors and institutions can help inform and influence change, while progressing our profession. As Bunny exclaimed in Desk Set, “Peg, calm down! No machine can do our jobs!” This book inspires me to take “the human element” to the next level and continually develop myself and my staff because Bunny was absolutely right, no machine can do what we do, and I for one, aim to keep it that way.The book wraps up with a chapter on additional funding resources for staff activities and a chapter on how to go forward in a world where “rapidly changing technologies, combined with unprecedented access to all types of information, are causing myriad societal changes” (p. 125). Unlike the characters in


Though foreign body (FB) aspiration or ingestion is not uncommon in children, a straight pin as the culprit FB is rarely seen. The nature of such a FB makes it sometimes difficult to diagnose and deal with, especially in children.Here we present such a case who was initially misdiagnosed with FB ingestion but turned out to be an aspiration case. Moreover, its remote location from the hilum made a more invasive surgical retrieval inevitable. A thoracotomy was finally performed to retrieve the pin. And the postoperative course was uneventful.For pediatric FB cases, especially in such a case, it is very important to diagnose timely and accurately. A multidisciplinary team approach would facilitate prompt and accurate diagnosis and potentially simplify treatment. Foreign bodies, either aspirated or ingested, are very common in children  tract. The patient was admitted to general surgery department for further treatment. The following day after admission, a second chest X-ray found it in its original place. However, with a high index of suspicion, the radiologist performed a fluoroscopy and found the FB, likely a straight pin, was actually in the posterobasal segment of the right lung Fig. . The posA literature search in PubMed was conducted using a word combination of “pin”, “FB” and “child”. We found no cases in the English-language literature of an airway straight pin in the child as the present one we report here. We discuss its diagnosis and management as follows.Foreign bodies, either ingested or aspirated, are very common in children  are shared by aspirated and ingested FB, yet some are unique  (Louie and Bradin Evaluation of a patient suspected of having a FB should generally include plain films covering the whole airway or the GI system. For radiolucent objects, contrasts are to be used for identification. Though, in most cases, a radiographic film can clearly show the location of the FB, it should be carefully interpreted to minimize misdiagnosis. In our case, the pin was lodged deeply in peripheral lung and it looked even below the right diaphragm on the initial posteroanterior abdomen and chest X-ray, as opposed to literature (Ilan et al. As far as the nature of an FB is concerned, the majority of foreign bodies in pediatric patients are toy parts, small pieces of food or others, like nuts, seeds and buttons. (Schneider The literature has reported involvement of interventional cardiologist during recovery for a peripherally lodged airway FB (Thatte et al. Though foreign bodies, either ingested or aspirated, are very common in children, a straight pin in a child is not usually seen in clinical settings. Sometimes a FB could not be easily identified if it is ingested or aspirated. As emergency as such a case is, a team approach can make a faster and more accurate diagnosis and provides best of care for these patients.


A number of programs have been developed to promote the contact between adolescents and mentally-ill patients, in order to break the stigma, improve understanding, promote mental health and prevent substance abuse. The aim of this study was to describe the experience of patients with schizophrenia, high school students, and their social context, participating in a short-term cohousing initiative.A qualitative case-study approach was implemented. Patients with schizophrenia from the San Juan de Dios Psychiatric Hospital, female students from Almen High School, and participants from their social context  were included, using purposeful sampling. Data were collected from 51 participants  via non-participant observation, focus groups, informal interviews, researchers’ field notes and patients’ personal diaries and letters. A thematic analysis was performed.The themes identified included a) learning to live together: students and patients participate and learn together; b) the perception of the illness and the mentally-ill: the barrier between health and disease is very slim, and society tends to avoid contact with those who are ill; c) change: a transformation takes place in students, in their self-perception, based on the real and intense nature of the experience; d) a trial and an opportunity: patients test their ability to live outside the hospital; e) discharge and readmission: discharge is experienced as both a liberation and a difficulty, whereas relapse and readmission are experienced as failures.Our findings can help us to better understand schizophrenia and encourage a more positive approach towards both the illness and those who suffer from it. These results may be used for the development of cohousing programs in controlled environments. Schizophrenia is a psychiatric disorder characterized by delusions and hallucinations (positive symptoms), accompanied by impaired motivation, social withdrawal (negative symptoms), and cognitive impairment ,2. The pSchizophrenia occurs worldwide, with a reported incidence of roughly 15 men and 10 women per 100.000 population per year, and a point prevalence of 4.6 per 1000 individuals . GeneticHowever, according to current psychiatric and medical views, schizophrenia cannot be explained merely by biology or the environment . Other iIndividuals with mental illness may be subjected to prejudice and discrimination from others and, as a result, may internalize feelings of devaluation –25. Prevhttp://sanjuandedios-mondragon.com/], via its program “Meet the Hospital” , with a severe mental disorder , particiStudents from the AH, in their first year of high school baccalaureate (aged between 16–17 years), participating in a “Meet the Hospital” program at the SJPH, signed the informed consent and were granted permission to participate by their parents.bInvolvement of participants from the patients’ context.The social context of the patients included professionals of the SJPH, who were involved in attending the health needs of patients participating in a “Meet the Hospital” program at the SJPH, and who signed the informed consent.cInvolvement of participants from the students’ contextThe students’ social and family context was comprised of: students’ parents who were participating in a “Meet the Hospital” program at the SJPH, and who signed the informed consent, and student’s teachers who were participating in a “Meet the Hospital” program at the SJPH, and who signed the informed consent.The patient exclusion criteria were: a) the presence of cognitive disorders, b) difficulties in comprehension and communication, c) the presence of mental crises and relapses, and d) refusal to participate in the study.A purposeful sampling strategy was employed ,49, whicWe contacted 18 high schools which, at the time of the study, were participating in the “Meet the Hospital” program of the SJPH. Of these, only Almen High school, agreed to participate in this study. In total, 10 teachers and 64 students from the first year of high school baccalaureate studies (aged between 16 and 17 years old) and who had participated in the SJPH program were offered the opportunity to participate in this study. Ultimately, 9 students and 6 teachers agreed to participate. Once the students were incorporated into the study, the parents were contacted and invited to participate. As a result, 11 family members of students were recruited. At the hospital, contact was made with 21 patients who were participating in the “Meet the Hospital” program. Of these, 15 agreed to participate. Once the patients in the study were identified, 17 hospital professionals who had a care relationship with the patients were offered to participate, of whom 11 eventually accepted. Finally, 51 participants were included within the sample and none withdrew from the study .The researchers approached a) the medical director of the SJPH, who acted as an intermediary to facilitate contact with patients and professionals and b) the director of the AH, and the director of studies, to enable contact with the students, the students’ parents and the high school teachers. Subsequently, the researchers explained the purpose and design of the study to the patients during an initial face-to-face contact session. Separate informative sessions were held for the patients, their legal tutors, the health professionals, students, teachers and parents from the AH. Thereafter, another group information session was performed with students, their parents, and high school teachers. During these meetings, the study was described and questions were answered. Finally, the participants were invited to participate in the study. These informative sessions took place at the hospital and at the HA.The research team consisted of six members (three women and three men), three from SJPH , one from the Hospitaller Order of Saint John of God Foundation (EGG), and two from Rey Juan Carlos University . Two members were psychologists, one was a physiotherapist, two were occupational therapists, and one was a nurse. Four members of the team had clinical experience in mental disorders and psychiatry , psychogeriatric (DPC), and rehabilitation (EGG). The remaining authors had no previous contact with any of the participants.Data were acquired over a period spanning seven months to one year, from September 2015 until March 2016. The objective of this case study was to obtain an in-depth multi-perspective holistic enquiry regarding the phenomena of interest, entailing the need for multiple data sources and multiple data collection tools  47]..47].Observational data collection is based on the systematic, detailed observation of people and events in order to explore behaviors and interactions within the participants’ own context . In thisDuring these observation periods, researchers used their field notes to record numerous details, such as: the physical layout of the place, the people involved, the activities that took place, the actions and activities performed, the sequencing of events, and the emotions expressed . During Focus groups (FGs) were conducted to examine different perspectives within the same group, acquire understanding of the problems faced by the group and facilitate the identification of values and norms ,52. In tThe FGs were conducted by a moderator following a uniform structure ,52. The In the patient FG, researchers took into consideration the listening, processing and conversational skills of the individuals with schizophrenia. The researchers asked concise questions, and rephrased or repeated these as necessary . Also, qFocus groups were conducted in Spanish, and were audio recorded. Permission for these recordings was sought before the recordings began.We also collected personal letters and diaries provided by the patients and students, and the researchers’ field notes. The participants’ personal letters and diaries provided a rich source of information as they described personal experiences from the participants’ point of view  See Tab.A thematic, inductive analysis was performed ,53. ThisComplete and literal transcriptions were drafted for each of the FGs, informal interviews, researchers’ field notes, and for the participants’ letters . Thematihttp://www.equator-network.org/) and the recommendations for the design of Case Study Research in health care using the DESCARTE model  were really good with us” (Patients focus group).Another common point raised was that both groups were able to learn from one another. During the cohousing initiative, the students and patients shared time, space and performed activities together that favored the exchange of experiences. Many of the conversations were focused on how they were living, what they did before being hospitalized or before participating in the study, or regarding their past and their family. Together with this exchange, the psychologist performed sessions with the patients and the students, both separately and together, in order to facilitate the adaptation, emotional control and management of conflicts. As a result, they learnt together. On the one hand, most students acknowledged that taking decisions (using drugs) always had consequences and, on the other hand, all the patients described how, on many occasions, they had made mistakes, regarding their behavior with their family and their drug addiction: “I am afraid of making decisions, but I am even more afraid of freezing and doing nothing.” (Letter by a student), “They have seen people who were like them and who have taken the wrong steps, ending up how they are now.” (Parent focus group). Furthermore, they learnt to evaluate their capabilities: “With them, everything is out in the open, you can’t fool yourself, you are what you are, and if you are not prepared, this becomes visible during the cohousing experience, and if you cannot manage a few days, how are you going to live outside on your own?” (Patient focus group)The students described a change in the way they view those who are ill. Before they branded them as being “crazy”, aggressive, doing odd things, trying to grab attention on the street, walking strangely, people who acted clumsier while doing things and while speaking: "… they have transformed from being ill to being normal people.” (Student focus group). The final consequence of this was that they were scared and avoided contact with those affected: “They took care of us much more then we took care of them. They had no problem from the beginning, [they didn’t experience] the rejection that perhaps we have since the beginning.” (Student focus group). Afterwards, the ill individuals were described as: “very good people”, and “not inferior”, or, in the words of one of the students: “they can have difficulties but that doesn’t mean that they do things wrong”. Even the parents described how their daughters had modified their perspective: “When my daughter sees someone who is ill, instead of saying ‘that person is crazy or a madman’, she now says that that the person is ill, in need of treatment and that the person is going to be able to live a normal life like the rest of people.” (Parent focus group). Furthermore, students remarked that mental illness has nothing to do with malice or being bad people: “If those who are ill get aggressive it’s because you have done something to them. It’s unusual for them to do or say something to you for no reason. Also, not just because you are mentally ill are you going to be bad. There are many normal people who are much worse.” (Student focus group).During the different stages of data collection, the professionals and parents described the existence of a very fine frontier between being healthy and being ill, and that this can happen to anyone: “Until it happens to you, you aren’t aware of how easy and how common it is to have a mental illness.” . It is not something that can be controlled or avoided: “Any day you can have a bad situation and then, suddenly, bam! They diagnose you and you are now mentally ill.” (Teacher focus group). Participants acknowledged having difficulties trying to recognize who was ill just at a glance: “On the streets, in normal life you cannot distinguish who is normal and who has a mental illness.” (Student focus group).Students mentioned how, in society, contact with those who are ill is avoided, it is generally thought that mental illness “is contagious”. It is said that if you are in contact with ill people, something rubs off, therefore, the solution is to keep a distance from them: “The first thing they told me when they knew I was going to the cohousing project was: ‘let’s see if you come out a bit affected’. I don’t think they really mean it, but that’s what they say to you.” (Student focus group). The society does not provide a real image of patients, they project a distorted and grotesque image: they are always the bad ones, the crazy ones, bringing up thoughts of asylums, or as people who may harm you, etc. This is what is projected in films, in the news etc., however, it is not a reflection of real life: “People, society, they don’t know what they are really like, they have no idea. They just say, “they are mad”, full of complexes… In the end, people talk without knowing.” (Student focus group).Students remarked that a change and a transformation had taken place within them. They felt more self-confident but, at the same time, they had many doubts, questioning everything about their life: “It’s like someone has removed a bandage from in front of my eyes” (Student focus group), “It was like having lived in a bubble. What I thought was life was not truly real…” (Student focus group). The contact with patients has made them reflect on many dimensions of their life: “It has been like an existential stir.” (Teacher focus group), “You couldn’t stop thinking that this was really harsh, everything they have lived through and suffered from. How can I say that my life is difficult? There came a time when I didn’t even know who I was or what I really wanted.” (Student focus group). Furthermore, for these students, living with patients was like seeing themselves in a mirror. Some described how, at times, they felt ridiculous for leading a life with commodities, considering that they had been wasting their life: “I realized that I didn’t recognize myself, as if I were mistaken all this time.” (Student focus group), “You hear so much and you see that you have your whole life ahead of you yet, you waste your time with silly things…” (Student focus group).The parents and teachers described perceiving students as more mature, by discussing their positions, making decisions, and reflecting upon their motivations: “We were talking about going to university, choosing a career and she said she was scared of taking steps forward, but she was even more scared of not taking them”. (Parent focus group). Some parents were surprised by this acquired maturity and the harshness of this new perspective: “My daughter told me… The world is no longer all peaches and cream as we thought, but that does not mean that it is bad”. (Parents focus group). For both the parents and the teachers, the cohousing experience impacted the students to such a great extent because it made them undergo very emotionally intense experiences: “One week after the cohousing experience my daughter came and told me how one of the patients explained to her the correct way to commit suicide, how the arm should be cut longitudinally, not perpendicularly, so that that way they wouldn’t be able to stich and repair the artery… She is 17 years old, she shouldn’t know this…”(Parents focus group),  (Student focus group). This intensity is due to the “real” nature of the experience: “… it’s not a lesson from a book, they have lived with mentally-ill people, they have seen the consequence of making decisions first-hand. The key has been the experience, what they have gone through is etched in their memories forever.” (Teacher focus group).The cohousing experience was perceived as both a test and an opportunity for patients. Thanks to this experience, it was possible to test the patients’ capabilities under controlled conditions while at the same time overcoming barriers.The patients perceived the cohousing experience as an opportunity for demonstrating their ability to live with healthy people, work in a team, and refrain from substance abuse: “It’s an opportunity that they have given us and I don’t plan to waste it, I shall demonstrate to both them and myself that I can do it” . It was a way of demonstrating that they are prepared for discharge. Also, it was perceived as a test to be able to live with others outside the hospital, and discover their limits. In this test, there were risks of failure, and uncertainties, because not everything is controlled : “It’s an opportunity but at the same time a test. A test that you can be successful with or mess up… I was very unsure regarding what would happen… would I be able to do it? (Patient focus group). On the other hand, this enabled them to test themselves under controlled situations, before the “official discharge”. In this manner, if they did not succeed, they knew they could return to hospital, without considering this a readmission or a relapse: “It is like a rehearsal, where you can see for yourself what it can be like to not live in the hospital… it gives you an idea of what it will be like outside, and on top of it all you feel anxious as you know that if you fail, and you get put in again, what will they say about you, the looks and comments you will get from other people.” Patient focus group).Cohousing represents a step closer towards being discharged. However, a flip side to discharge exists. On the one hand, it can signify recovering “the lost freedom”, abandoning the norms and the hospital control: “This is like a jail, only worse. In jail, you know when you get in and when you are getting out, not here…” (Patient focus group). However, at the same time, many patients avoid leaving the hospital, as they are afraid of rejection, using substances again, or that the daily responsibilities may go beyond their capabilities: “…I have fought for discharge, and I wanted it, but then I have gotten out and realized that I no longer want it. Nobody helps me, living outside [the hospital] is very complicated, it’s expensive, you don’t have the benefits that you may have at the hospital…” (Patient focus group).During the cohousing experience, one of the patients suffered a crisis and had to be taken to the hospital and abandon the cohousing program. As a result, patients began to narrate their own past experiences of being admitted to hospital and suffering relapses. Thus, for a patient who has been discharged, readmission due to a relapse is experienced as a failure, as it demonstrates the patient’s inability to live by their own means. Furthermore, together with the feelings of failure, there is a feeling of blame: “You cannot avoid feeling guilty, nobody makes you leave, you do it and you want to get out but you don’t realize that you are unprepared… Guilty for not having foreseen it.” (Patient focus group). Patients acknowledged that, in previous readmissions, they felt they had not done all that was in their hands to remain discharged from hospital, i.e. to avoid relapsing and avoiding substance abuse: “I messed up, after all my efforts, I lost an opportunity, I have done things wrong.” (Patient focus group).The most relevant results of this study include: students and patients participating and learning together; a slim barrier between health and disease, a transformation taking place in students, regarding their self-perception, patients testing their ability to live outside the hospital, and discharge, experienced as both a liberation and a difficulty, whereas relapse and readmission are experienced as a failure.Our results show how, during the cohousing experience, patients and students relate with each other, learning and overcoming barriers together. A number of programs have been developed to promote the contact between adolescents and patients in order to break the stigma, improve the understanding of the mentally ill, promote mental health among the young and prevent substance abuse –32. PrevOur results reveal a change in the female students’ vision of the patient and mental illness. However, with the design used in this study, we cannot describe how this change of perspective has occurred, nor whether this change will be long-lasting. However, these findings do seem to be relevant for participants who have taken part in the experience. The students also perceived that the overall society continues to reject mental illness. In Spain, Muñoz et al.  reportedOur results reveal that the experience of patients living together with students has provided an opportunity to overcome barriers, helping patients to demonstrate their ability to live outside the hospital, relate with healthy people, share, work on common goals, and establish friendships. Anderson  describeOur results showed that patients feel that their discharge is both a source of liberation as well as a risk. The fear of failure, of having a relapse, and facing readmission is very real. At the SJPH, before hospital discharge, patients receive home support, living with other patients in the same apartment under regular supervision. However, there is no intermediate step between being at hospital and receiving supported housing. At the time of the study, patients diagnosed with schizophrenia at the SJPH (n = 200) presented between 32–36 hospitalizations per year, remaining in the community for 33 months, on average, without the need for being readmitted. Previous studies ,73 have It is important to note that, in case studies, different units of analysis are included which enable us to understand the phenomenon in greater depth, as well as serving as a triangulation technique to control the quality of the study and provide information from another perspective that is different to that of the patients ,56,57.In the first place, during the study we were unable to include participants from the patients’ family environment, as they declined to participate in the study. Indeed, prior studies ,77 have Our findings can help us to better understand the relationships and perceptions between people with mental illness and those without. There are different forms of supported housing such as Housing First , PermaneS1 File(DOC)Click here for additional data file.S2 FileHospitaller Order of Saint John of God.(PDF)Click here for additional data file.S3 File(DOC)Click here for additional data file.S4 FileEnglish version.(DOC)Click here for additional data file.S5 FileSpanish version.(DOC)Click here for additional data file.S6 FileEnglish version.(DOC)Click here for additional data file.S7 FileSpanish version.(DOC)Click here for additional data file.S8 File(PDF)Click here for additional data file.S9 File(PDF)Click here for additional data file.S10 File(PDF)Click here for additional data file.S11 File(DOC)Click here for additional data file.S1 Photo(PDF)Click here for additional data file.S1 Fig(DOCX)Click here for additional data file.


The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Epigraph vaccine antigens are functionally similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Epigraph furthermore has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraph was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a  HIV is highly variable, largely as a consequence of immune selection acting on this highly mutable virus during chronic infection12357Mosaics and Epigraphs solve essentially the same optimization problem (PTE coverage), and are thus expected to behave the same way experimentally. Mosaic antigens have already been designed, synthesized, and tested, and have shown promise on a variety of fronts. When expressed, Mosaic antigens have folded well in terms of binding discontinuous antibodies, and are highly immunogenic, eliciting both T-cell and antibody responses81081013148101113Despite the similarities in the overall optimization criteria, Epigraphs provide substantial advantages over our original Mosaic strategy. Mosaics use a genetic algorithmRecently there has been resurgence of interest in T cell-based vaccines. SIV vaccine antigens presented in rhesus macaque cytomegalovirus (RhCMV) vectors generate prolific T-cell responses that enable stringent control and progressive clearance of pathogenic SIV upon infection in over 50% of vaccinated monkeys. These responses violate traditional paradigms of T cell-mediated immunity, and provide new impetus for exploring T-cell vaccine approaches21162324Here we applied Epigraph to provide potential solutions to two outstanding vaccine design problems. First, we describe a Tailored Therapeutic Vaccine (TTV) approach. In contrast to a vaccine that prevents infection, in therapeutic setting it is possible to obtain sequences from the infected person who will be treated, and attempt to match their infecting strain as closely as possible to the vaccine. It is not currently feasible to make a new matched vaccine for every person you treat. The TTV approach enables the design of a small set  vaccine antigens, a practical number for manufacture. Then, for each individual, the best two or three antigen subset of these six can be selected to provide a “tailored” match to viral sequences sampled from the patient to be treated. The Epigraph-based TTV code optimizes the set of vaccine antigens for manufacture, such that the set will sample the diversity of the target population, and enable the best vaccine matches overall for infected individuals in the target population. Here we apply TTV approach to HIV, though the strategy is general. A single TTV design run can loop over more than a thousand basic Epigraph runs, so the computational efficiency is essential to complete the Epigraph design.Filoviradae family, which includes ebolavirus and marburgvirus viruses, as well as other related viruses that can cause fatal hemorrhagic fevers in human and non-human primates. First we used Epigraph to define the most conserved regions of the filovirus proteome, then we used it to design antigens that would best cover the diversity that was found in those regions. We explored dozens of design strategies to finally identify a vaccine solution that met three criteria. First, we felt it was critical that the potential T-cell epitope coverage of the ebola virus species, that has historically seeded most outbreaks, not be compromised. Second, we wanted the design to have the potential to elicit responses against of the full range of known diversity of viruses in the Filoviradae family. Third, we made sure that the conserved regions that were included spanned relatively large stretches of protein, so that epitopes representing a broad spectrum of human leukocyte antigens (HLAs) would be included. Exploring the combinatorics of the many design options we considered to meet these criteria would have been prohibitive using the slower Mosaic code, but through systematic use of Epigraph, we were able to identify a promising design strategy that met our 3 criteria.We next explored the problem of how to design a vaccine that could cover the viral diversity found in the entire known T-cell epitopes are very densely packed in HIVi.e., every k-mer) to be a potential epitope. We usually set k = 9 as the length of potential T-cell epitopes (PTEs), as this is the optimal length of most cytotoxic T-cell Class I presented epitopes5k = 9 are still very good for other common epitope lengths of 8–12 amino acids . The input proteins do not have to be aligned, but they can be, as will be discussed below. Each sequence in the set is decomposed into all possible 9-mers, and the number, n, of recurrences of a particular 9-mer in the sample population is tallied. Each unique 9-mer found at least once in the sample population will be associated with its frequency in the population. For instance, if there are 1000 sequences in the sample population (N = 1000), and a particular 9-mer was found exactly matched in 200 of those sequences (n = 200), then the frequency of that 9-mer is n/N = 0.2. We characterize the potential cross-reactivity of an antigen by the sum of the frequencies of all the 9-mers in the antigen sequence; if we divide this quantity by the sum of frequencies of all the distinct 9-mers in the population, that provides the coverage score.The first step in Epigraph design is to assemble a representative sample of Next, as illustrated in in silico generated recombinants, and then selects those candidates with the best coverage for the next generation from among those poolsk-mer overlap graph . As no and based on this trade-off, select a threshold no to use for a final Epigraph run.While Epigraphs generally disfavor rare epitopes, we can constrain solutions to strictly avoid them. The Epigraph tool suiteno = 1, so that each PTE included in the Epigraph sequences appears more than just once in the sample target population. But users are encouraged to use a larger cutoff, as long as there is negligible cost in terms of coverage. Excluding rare variants also speeds up the computation time , and a sample of a patient’s infecting viral quasispecies sequence is available . Given current technology and costs, it is not feasible to create a de novo vectored vaccine for every subject. It is feasible, however, to sequence a sample of each patient’s virus. Thus the more modest goal addressed here is to manufacture an affordable pool of m distinct vaccine antigens, from which only a subset (n < m) is delivered to each patient, with the subset chosen to maximize PTE coverage of the patient’s viral sequences by the selected Epigraphs.A tailored therapeutic vaccine (TTV) is intended for a treatment situation in which the patient is already infected . Epigraph is separately applied to each cluster to obtain a centroid sequence for that cluster; i.e.,qi is obtained by maximizing the coverage over the sequences in i'th cluster provided by the PTEs in the antigen set {qo, qi}. The process is iterative: the population sequence set is re-clustered by re-assigning each sequence to the qi that maximally covers the PTEs in that sequence, and the new assignments lead to updated qi’s, and so on until convergence. Finally, {qo, q1, …, qm−1} is the set of m antigens that are manufactured.We explored several alternative strategies to achieve better coverage of sequences from the population of interest. The best of these, which is detailed in Algorithm 4, employs a clustering strategy. We start with a single antigen sequence The outcome can be sensitive to the initial conditions , so we perform 100 complete runs using different starting sequences, and retain the best one as our solution. Given the number of iteration cycles in a single run, and the number of repeat runs with different initial conditions, the computational speed of the Epigraph algorithm is critical.We applied TTV to three potential HIV target sequence populations for treatment studies: 189 contemporary B-clade sequences sampled in the United States, 199 contemporary C clade sequences sampled in Southern Africa, and 2015 Los Alamos HIV database 4596 global M-group Gag sequences . Gag was21n, increasing the size of the manufactured pool from m = 2 to m = 6 increases coverage (by over ten percent for the M-group) without increasing the number of extra PTEs. Compared to the full-length Gag, the conserved-region p24 achieves improved coverage and dramatically reduced extras. 2931323132Here we propose an Epigraph solution to a conserved-region pan-filovirus vaccine. The Epigraph tool was used for two purposes: first to define conserved regions within the proteome, and then to design the best combination of antigens within those regions for maximizing PTE coverage. A T-cell based Epigraph design may be particularly useful for viruses in the family Filoviridae family have caused nearly 50 outbreaks in humans since their discovery in 1967, the most recent of which was the devastating 2014 West African epidemic34Ebolavirus genus virus: Ebola virus (EBOV), Sudan virus (SUDV), Reston virus (RESTV), Taï Forest virus (TAFV), and Bundibugyo virus (BDBV)Marburgvirus genus: Marburg virus (MARV) and Ravn virus (RAVV)Cuevavirus, discovered in bats in the Iberian PeninsulaViruses in the Filoviridae species/variantsMost vaccine efforts (reasonably) focus on EBOV, SUDV, and MARV, as these viruses are historically the most frequent causes of these outbreaks30Filoviridae family. This was based on a comprehensive set of full genome sequencesWe first used PTE coverage by full proteome Epigraphs as a means to define the four most conserved regions across all members of the Filoviridae family. More specifically, our criteria are to: Preserve PTE coverage of EBOV, the most common species in human outbreaks Maintain excellent PTE coverage of SUDV and MARV, which also have caused recurrent outbreaks; andgiven the constraints imposed by the first two criteria, provide extensive PTE coverage of all other Filovirus species.Having identified conserved regions, our next step was to design the vaccine. Because a future outbreak is most likely to be the result of a virus from one of the common species, we did not want to compromise the cross-reactive potential for those viruses. But, as discussed above, it is also possible that a future outbreak may more closely resemble rare-in-human, or even as-yet-undiscovered, members of the Filoviridae PTE coverage, and we systematically explored the outcomes of different design strategies, including optimization of Epigraph vaccine antigens using the 34 outbreak sequences simultaneously, as well as combinations that used serial optimization, either starting with a natural sequence, or starting with an Epigraph solution based on the 5 representative sequences selected from members of the Ebolavirus genus, or on a set of 8 representative sequences that sampled filovirus diversity. We compared PTE coverage based on full proteins that have been commonly used in vaccines, to the coverage based on conserved regions. We also explored the impact of optimization on imperfect matches, and exclusion of rare epitopes. A priori, we didn’t know which of these strategies would provide the best solutions, and in these series of comparisons, dozens of Epigraphs runs were conducted and compared; the speed of the Epigraph code enabled a thorough and systematic exploration of design options. In Ebolavirus Epigraph solution; this was fixed  to enforce good coverage of this historically important genus, the cause of many highly lethal outbreaks. Then a second Epigraph sequence was designed that offered maximum complementary coverage of the full 34 sequence outbreak set relative to sequence “a”, for use as a bivalent vaccine. The E solution again started with “a”, and two Epigraphs were simultaneously solved that again offered maximum complementary coverage of the full 34 sequence outbreak set relative to “a”, this time intended for use as a trivalent vaccine.There are many possible paths to achieve good Filoviradae family that have not yet been encountered. In particular, a trivalent conserved-region Epigraph vaccine achieves (>90%) PTE coverage of viruses across the Marburgvirus and Ebolavirus genera, with significant cross-reactive potential against the very distinctive Cuevavirus . This high performance at low cost expands the design space for novel vaccine approaches. Our Epigraph vaccine design tool suiteBy maximizing PTE coverage, polyvalent Epigraphs are markedly more efficient than natural sequences in making use of the sequence space available in antigen inserts. The most common forms of epitopes are favored, while rare type-specific epitopes, which are found in virtually every natural HIV strain, are disfavored, and can be explicitly excluded. If a variant of an epitope is already present in one antigen, other antigens in the set will tend to pick up other common variants. Such epitope complementarity in Mosaic antigen sets has been shown experimentally to extend both the breadth and the depth of the vaccine response in animal models1013i.e., extra) epitopes in a vaccine. The impact of mismatched epitopes on T-cell responses is not understood, but can now be experimentally evaluated in the context of antigen presentation in RhCMV vectors in NHPs, where the effect of varying these parameters on protective efficacy be tested experimentally.We incorporated Epigraph code into our TTV design algorithm, to use PTE similarity as a foundation for defining clusters of viruses, an immunological perspective, rather than less relevant Hamming or phylogenetic distances. TTVs are therapeutic vaccines that could best cover the population diversity for the purpose of tailoring a vaccine to individual patient’s infecting virus within the context of manufacturing a limited and feasible number of antigens. We also explored the idea that in designing TTVs , the benefits of increased PTE coverage should be balanced with the cost of including mismatched  = n/N.A sample set s. For example, if s = VTSSNMNNADSVWLR…, then sets ∈ s ∈ e appears in multiple sequences, it still appears only once in We will write q is a sequence that resembles a natural protein but contains PTEs that correspond to the most frequently appearing PTEs in the population sample q, we say that an antigen q exhibits good coverage if the f(e)’s are large for the e’s in An artificial antigen q, and the denominator is the sum over all PTEs. This coverage corresponds to the total cross-reactive potential of all the epitopes in the vaccine antigens. We don’t have a detailed model for how reactive each epitope is, or even for which k-mers are true epitopes;The numerator is the sum of the frequencies of PTEs that appear in k-mers equally. For a highly immunogenic protein like HIV-1 Gag, T-cell epitopes have been identified in the literature  if they overlap by k − 1 characters, as illustrated in the k-mer overlap graph, which is closely related to a de Bruijn graph44The main idea in Epigraph is that we can express this formulation as a directed graph . Each nopath through the graph is a connected sequence of nodes e1, e2, …, eL: there is a directed edge from e1 to e2, from e2 to e3, and so on until the last edge connects eL−1 to eL. Such a path corresponds to a sequence of L + k − 1 characters, which defines the artificial antigen q. The coverage associated with that antigen is directly proportional to the sum of the frequencies associated to the nodes in the path: f(e1) + f(e2) + f(eL).A k characters in each sequence. Epigraph (see Algorithm 1) finds a path P from Begin to End that optimizes the total frequency ∑e∈Pf(e) of epitopes in that path. The algorithm for finding the optimal path is straightforwardly equivalent to well-known algorithms in graph theory47F(e) for all the nodes, where F(e) is the maximum total frequency over all paths that end in e. The backward loop builds the path that achieves the maximal score.For computational convenience, we add Begin and End nodes to the graph, connected respectively to the first and last e) be the set of predecessors of node e: that is, the set of nodes e′ for which there exists a directed edge that connects from e′ to e. Then we haveLet e) is empty, then we define F(e) = f(e). In particular, F(Begin) = f(Begin) = 0. If all of the sequences in S contain only amino acid characters, then the Begin node will be the only node with no predecessors. If there is a non-amino-acid character  in any of the sequences, then the PTE immediately after that character might also lack a predecessor. For a directed acyclic graph, there exists a “topological ordering” of the epitopese1, e2, …, with the property that if  is a directed edge, then i < j. By proceeding in this topological order, we can straightforwardly evaluate If the set of predecessors F(e) for all the nodes e, we will start at the node Having evaluated q of p + k − 2 characters that optimizes the epitope coverage by an intact artificial protein that resembles a natural protein. If the argmax operator does not have a unique value, there are multiple solutions, all equivalent and optimal in the sense of coverage.If the set k. For this case, we developed a heuristic scheme to “de-cycle” the graph, by iteratively identifying cycles and then removing low-value edges until no cycles remain (see Algorithm 2 and Methods: De-cycling).If this directed graph has no cycles, then Epigraph finds a path that maximizes F(e) in x(e) for all epitopes in the graph:As an aside, we further remark that the logic that defines ea, eb) is a directed edge in the graph, then x(ea) < x(eb). In particular, if we use x(e) as a horizontal position associated with node e (which we do in If (f(e) ≤ fo = no/N, where fo is a cutoff frequency (and no is a cutoff count), and N is the number of sequences in the population.If a user wishes to exclude rare epitopes, they an do this by selecting a cutoff frequency for exclusion for an Epigraph run. The Epigraph tool suite enables a user to explore of the cost in terms of overall coverage as the cutoff frequency increases , to makek-mer is found directly repeated in the same sequence; this is not common, but it does happen. In the Los Alamos HIV database 2014 alignment, out of N = 4250 HIV Env sequences, 91 of them (2.1%) have at least one 9-mer directly repeated in a sequence. Similarly 0.3% of Nef, 0.8% of Pol, and 1.3% of Gag sequences, carry such repeats. A more common way for cycles to arise, however, comes from effective repeats of an epitope across multiple sequences.The population of sequences gives rise to a directed graph, but this graph may contain cycles, and the Epigraph algorithm requires that the graph be acyclic. One way cycles can arise is when an identical k , the graph is often very nearly acyclic, and can be made acyclic with only a few perturbations to the graph. The optimal solution to this perturbed graph is then taken as a nearly-optimal solution to the original graph. The problem of removing the least number of edges to produce an acyclic graph is equivalent to the NP-hard “minimum feedback arc set” problem49On the other hand, we have found that, particularly for larger values of ea and eb are two nodes in the same component, then the directed path from ea to eb can be merged with the directed path from eb to ea to form a cycle that includes both ea and eb.To eliminate cycles, we first have to find cycles, and to help with this task, we decompose the graph into “strongly connected components”  – a task that can be performed in linear timeea, eb) we define a value, based on f(ea) and f(eb); then we choose the edge with the smallest value and remove it from the graph. A very simple and  effective heuristic is to take the value to be the sum f(ea) + f(eb). In our experiments, we employed a slight modification of this heuristic. If ea is the sole predecessor of eb, then cutting edge  will isolate node eb, so we add a further cost of f(eb). Similarly, if eb is the sole successor to ea, then we add f(ea). See Algorithm 2 for details.Each time a cycle is located in the graph, we choose one of the edges in the cycle to remove from the graph. This choice is heuristic, but since cutting edges has the effect of isolating nodes, we seek cuts that isolate low-value nodes. For each edge -sequence problem, we try to optimize the complementary coverage, and pick up to the extent possible high-frequency PTEs that were not sampled in the first m′ sequences. This is done by setting the f value of the already-covered PTEs to zero. The graph structure is the same, but the update of the cumulative scores is based on these new f values. Although revisiting epitopes from the {q1, …, qm′} sequences is allowed if essential to complete the path, it is discouraged because there is no gain in the coverage score. Specifically, define the modified frequencyTo find a cocktail of and, as in m′ = 1 solution using Epigraph on the original frequencies f(e); then extend to m′ = 2, 3, …, m by optimizing complementary coverage at each stage, using the modified f*(e). The m = 1 + 1 column in Thus, for instance, we can find an q1, q2, …, qm, we can go back and recompute a new solution for q1. This is done by starting with the original frequency values for each of the epitopes, but setting to zero those epitopes that are covered by q2, …, qm. The optimization of this complementary coverage problem leads to a new q1. One can loop through all of the initial solutions this way, each time optimizing the appropriate complementary coverage.Once an initial polyvalent solution has been determined, iterative refinement of sequential solutions can improve the final coverage. Given initial sequences e.g., one can use a consensus, natural or Mosaic solution as an initial sequence. The iterative refinement scheme can also be applied to other initial conditions; m′ = 1 solution, use a random sequence for q1. With this as a starting point, sequentially add new sequences q2, …, qm, followed by iterative refinement until convergence is achieved. We can do this for many random initial sequences, and keep the solution that gives the best coverage. Iterative refinements with multiple trials were used for the m = 2 column in Multiple trials can also be used to improve coverage. Here, instead of using Epigraph to obtain an How to cite this article: Theiler, J. et al. Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci. Rep.6, 33987; doi: 10.1038/srep33987 (2016).


As the life expectancy of people with intellectual disability (ID) has progressed, they have become similarly at risk of cancer as individuals of the general population. Epidemiological studies indicate a reduced incidence and mortality from lung cancer in the total population of persons with ID. However, the pattern is heterogeneous and the risk is strongly correlated with the impairment level; persons with mild intellectual impairment have higher cancer risk, and this subgroup also has the highest tobacco consumption (the major risk factor for lung cancer) compared to individuals with more severe impairment. Clinical presentation of lung cancer in persons with ID is often atypical, with symptoms frequently hidden by the mental state and communication impairments. Treatment can be impeded by incomplete understanding and lack of cooperation on the part of the patient; nevertheless, general principles for treating lung cancer must be applied to persons with ID. Early diagnosis and implementation of an adapted treatment plan may result in lung cancer outcomes similar to those of individuals in the general population. Physicians facing the difficult task of treating lung cancer in persons with ID are called to carry out their mission of care in a responsible, free, and creative way. As the life expectancy of people with intellectual disability (persons with ID) has increased over the last few decades , they haPersons with ID are reported to have a nearly similar risk of developing cancer as individuals in the general population , 5. HoweThe present article focuses on the frequency of lung cancer in persons with ID, its diagnosis, and potential treatment difficulties, seeking to help improve overall clinical care of this important population.A search of the literature was conducted in two phases. First, a regular follow-up search of cancers in persons with intellectual disabilities was conducted for ten years by one author (Daniel Satgé). This search was performed every month on Medline using the words “mental retardation” and “intellectual disability” indexed with “cancer”, “malignancy”, and “tumor”. Second, a more specific search was performed to focus on lung cancer. In PubMed, we searched the terms “mental retardation”, “intellectual disability”, and “learning disability” with each of the terms “lung cancer”, “lung malignancy”, “lung tumor”, “lung carcinoma”, “lung adenocarcinoma”, “lung small cell carcinoma,” “lung carcinoid”, “lung sarcoma”, “lung fibrosarcoma”, “lung lymphoma”, “bronchial carcinoma”, “bronchial adenocarcinoma”, and “pleural mesothelioma”. On Google Scholar we searched the terms “mental retardation”, “intellectual disability”, and “learning disability” with “lung cancer”, “lung malignancy”, and “lung carcinoma”. These searches were not limited in the time of publication or language. Retrieved abstracts were scanned manually, and potentially suitable papers were collected. Cases where cognitive impairment occurred after the age of 18 were excluded, as well as patients with pure psychiatric conditions without intellectual disability. The extracted data were frequency clinical characteristics, treatment, and environmental and genetic risk factors.The search on PubMed provided 144 abstracts, of which 33 were retained. The search on Google Scholar found 23 abstracts, of which 11 were retained. Among these 44 abstracts selected in the second component of the search, 15 were not found in the first general follow-up search. Additional articles were identified through citations and references. In total, 76 articles were included.The frequency of lung cancer in persons with ID has not been evaluated through targeted studies. Nonetheless, data provided in studies based on all cancers in persons with ID provide helpful indications. The two available epidemiological studies on cancer incidence indicate a reduced frequency of lung cancer in the total population of persons with ID , 5. A reMortality data also indicate a lower frequency of lung cancer in persons with ID. A recent evaluation conducted in Leicester County, United Kingdom (UK), revealed that persons with moderate, severe, and profound ID exhibit a standardized mortality ratio (SMR) for all cancers similar to that in the general population, at 0.94. However, the SMR for lung cancer is reduced to 0.62  –9. SimilFurther, the risk for lung cancer in persons with ID strongly correlates with the severity of ID. In the Australian study, 6 of 7 lung cancers occurred in individuals with mild ID . In the Globally, the risk for lung cancer appears, in these studies, to be lower in persons with ID compared to the general population. We do not exclude the possibility of an underestimation of the burden of lung cancer, particularly in older studies. This is possible because, first, persons with ID had a shorter life expectancy only a few decades ago. Similarly, diagnostic tools, particularly medical imaging, were less available and effective during that time. However, digestive tract cancers were frequent in the same studies, indicating that other types of malignancies were not missed. Thus, we believe that significant underevaluation of the frequency of lung cancer is unlikely. Additionally, these works included a high proportion of individuals with moderate and severe ID in whom lung cancer is rare, which may lead to the false assumption that lung cancer is very rare in all persons with ID, including persons with mild ID. On the basis of the current literature, we may say that lung cancer appears less frequent in persons with ID compared to the general population, particularly for the 20% of those with profound, severe, and moderate ID and to a lesser extent for those with mild ID. Targeted studies are needed to assess the real risk of lung cancer in persons with ID. Various histological types have been reported: adenocarcinoma , small cThe major risk factor for lung cancer is tobacco smoking; infrequently, persons with mild ID are exposed to occupational carcinogens such as asbestos and may develop a lung carcinoma . OverallSmoking behavior is also related to the severity of ID; smokers are more common among individuals with mild ID. Further, smoking is more common among group of home residents than among those who live in an institution or those who live in their families, with rates varying from 3.8% to 20.8%. With the closure of long-stay institutions, more persons with ID are living in the community. Drinking alcohol, being sexually active, and having schizophrenia are also significant predictors of smoking among persons with ID .Interventions such as a smoking education course to lower tobacco use have been implemented among persons with mild ID leading to some success . HoweverThe population of persons with ID is highly heterogeneous when considering the cause of ID. In many patients, particularly those with mild ID, the causes remain unknown. For about one-third of patients, ID is attributable to one of nearly 2000 known genetic conditions. Nongenetic causes are perinatal, vascular, postinfectious, toxic, posttraumatic, and environmental . FMRP gene [Some studies have assessed cancer incidence among individuals with specific genetic conditions. An excess of lung cancer has been reported among individuals with Klinefelter syndrome in two epidemiological studies , 28. In MRP gene . FinallyMRP gene . The redChildren and young adults with other genetic conditions, such as Nijmegen syndrome  and ataxs complained of minor chest pain despite bilateral spread of the tumor, but his family did not believe it was a serious problem. The treatment team was surprised that he did not develop pulmonary and cardiovascular symptoms [Little data are available to document the clinical presentation of lung cancer in persons with ID. Presentation may be similar to that of nondisabled persons: cough, dyspnea, hemoptysis, and chest pain. However, symptoms are frequently concealed by the mental state and communication impairments. In particular, because many people with ID communicate pain and unease in unconventional ways that may not be readily understood or may not appear to express pain at all, a tumor may remain undiagnosed for some time. Among eight available reports with clinical history, two bronchial carcinomas were discovered on routine chest radiographs before a surgical procedure for another disease , 16. Onesymptoms . For twosymptoms , 43. Thesymptoms . In a sisymptoms . The sevsymptoms , 46. Thesymptoms .In general, the more severe the disability, the less clear the symptomatology, thereby introducing diagnostic challenges for patients with severe and profound ID. A patient who is unable to express his symptoms may present with mood and behavior modifications. He may behave aggressively, as was described in a 41-year-old man with a brain tumor , or remaAdditionally, families do not have specific knowledge of cancer risk in persons with ID. In residential homes, nursing homes, and supported living arrangements, staff members are less knowledgeable about signs and symptoms of cancer than is optimal , 49. TheIndeed, diagnosis delay is not specific to lung cancer and has been observed in a series of breast carcinomas  and in aGeneral principles for treating lung cancer must be applied to persons with ID. Treating a lung tumor is more difficult in adults with ID as compared with nondisabled persons. This is because, first, for many patients with ID the cancer diagnosis is delayed. When tumors are discovered at a late stage they must be treated with more intense therapeutic regimens , 45, 54.Communication between cancer patients and their caregivers is likely to be poor with persons with ID . In a stThe review examines an important and underrecognized topic that deserves our attention. As the life expectancy of persons with ID has significantly progressed, these people are now at risk of various cancers. We acknowledge that this first review on the subject has a number of limitations linked to the available literature. Although a 10-year follow-up of the literature on cancer in persons with ID in PubMed and in books completed by a systematic search with targeted keywords has been conducted, a limited number of articles were collected. Epidemiological data on cancer incidence and on cancer mortality are not focused on lung cancer. Such a focused study could provide additional data on cancer occurrence according to ID level, to the place of residence, and to associated risk factors. Studies in institutions that were conducted decades ago may result in an underevaluation of cancers, including lung cancers. However, as other cancers such as digestive tract malignancies have been reported in these works, it is likely that the underestimation of lung cancer is not significant. On the other hand, few case reports presenting unusual tumors in rare syndromes may lead to an overestimation of unusual histological types of lung cancer. Further, the few detailed reports do not enable us to draw conclusions on symptoms that lead to diagnosis or on treatment results. These gaps in knowledge show the need for clinical series that document symptoms, tumor histology, treatment compliance, and treatment results.Lung cancer appears to be less frequent in persons with ID compared to the general population, based on available literature. Lung cancer seems even rarer in persons with moderate, severe, and profound ID. As lung cancer is relatively uncommon in persons with ID and since symptoms are often atypical and less noticeable, diagnoses are often delayed. The possibility of a lung malignancy should be considered, particularly for persons with ID who smoke tobacco. Further efforts should be undertaken to lower their tobacco use. Treatment is difficult due to psychological and sometimes biological obstacles, which require adaptations to standard care plans. Two examples of carcinoid tumors show that lung cancer treatment outcomes can be as good among persons with ID as in the general population when the tumor is discovered early, when adapted care is given and if the person is able to cope with treatment.


It was late March 2014, and a small Ebola virus disease (EVD) outbreak had been reported a few weeks earlier in Guinea. The half-read pile of malaria journal articles on my lap provided the flight crew sufficient evidence to conclude there was a “tropical medicine guy” on the flight, just what they needed for their current dilemma. As I walked toward the front of the plane, I had a suspicion what the upcoming topic of discussion would be.“When I told company headquarters I was not flying this plane to Monrovia, they threatened to fire me,” the pilot anxiously greeted me and then added, “You know the first case of Ebola in Liberia was diagnosed a few hours ago. I can have us headed back to the U.S., especially if you agree. Doc, what do you think, should we really be flying to Liberia right now?”With important malaria-related meetings awaiting me in Monrovia and an understanding of the minimal risk a single, unconfirmed case of EVD posed to the pilot and crew, I replied, “I think you have nothing to worry about” and went on to explain the fundamentals (of what was known at the time) of Ebola virus transmission. Our plane was Liberia bound a few minutes later and, although I did not realize it at the time, that would be the first of many instances of Fearbola I would encounter in west Africa.In public health, one of the first rules of managing an outbreak is to communicate early, truthfully, and effectively. For public health workers, this involves conveying appropriate information related to disease manifestations and prevention strategies. During such a time, the press is also in the business of conveying information, but may do so with a different set of principles and objectives.In early Autumn 2014, the word “Fearbola” was popularized as a description of the public's reaction to the intensity and nature of the initial press coverage of a handful of EVD cases in the United States.Throughout sub-Saharan Africa, newspapers remain an important method of communication, with the trend of independent newspapers crowding out government-funded and controlled ones.4In late March and early April 2014, immediately after the announcement of the first case of EVD in Liberia, local newspapers displayed titillating front-page messages: “Ebola Terror Rages” (In addition, faulty public health messages were propagated from some periodicals, such as a front-page picture of a produce stand with the sign, “Please Use Gloves Before Touching Vegetables and Fruits” (Editorialists exploited the situation to convey reproachful religious messages. One declared, “Ebola virus which is almost becoming a national plague…clearly signals the need for caution to Liberians to lead lives that will avoid the wrath of God descending on this nation through plagues like Ebola and judgment like that of the twin cities of Sodom and Gomorrah.” Another article titled, “Liberians need Jesus to combat Ebola,” featured the quotes of a local educator placing blame on the country's sinners and their “total disregard for the Creator.”Such embellishments were not limited just to the initial weeks of the epidemic or to Liberia. In October 2014, one Sierra Leonean paper proclaimed, “Ebola victim rises from the dead,” alongside a dubious photograph probably borrowed from Hollywood (A misinformed, paranoia-driven community may pose danger beyond just disease transmission. In April 2014, EVD control efforts were jeopardized in Macenta, Guinea, when a group attacked a treatment site, alleging that foreign health-care workers had brought the disease.But the press can be used in positive ways and, to be fair, much of the local coverage in west Africa was responsible and accurate. Within a week of the country's first case, one Liberian newspaper page titled, “Fighting Against Ebola We Are Together,” incorporated the Ministry of Health and Social Welfare's messages about modes of disease transmission and provided prevention strategies, including what to do after contact with a potential case and a number to call for those with questions (International groups were also able to partner with the media. During the height of the epidemic, nongovernmental organizations, such as Internews, offered workshops to Liberian journalists who, in turn, used their platforms to educate about EVD. One campaign, which featured the slogan “Ebola Must Go,” was championed by the country's president, Ellen Johnson Sirleaf, and spanned multiple media formats beyond just newspapers, including music videos, radio jingles, billboards, Facebook, and Twitter. Agencies like the U.S. Centers for Disease Control and Prevention worked alongside the Ministry of Information, Cultural Affairs and Tourism of Liberia to ensure scientifically valid information was contained in daily press briefings.Since the waning of the EVD epidemic, efforts remain to provide sub-Saharan journalists skills to better cover scientific stories of public interest.


Systematic studies on the association between men’s sexual dysfunction  and marital conflict are emerging. However, the coping strategies adopted by wives in such circumstances are not commonly reported in the literature. Male sexual functioning is vital to the marital relationship, lack of it can result in intolerable cohabitation or relationship breakdown, and could also cause infertility, infidelity, and arouse stigma in Nigeria. The understanding of coping strategies by female partners could guide in the counselling and treatment of men’s sexual health problems. Effective coping has the potential to lessen or prevent negative outcomes, and thereby could reduce marital conflict.This study examined the coping strategies adopted by women whose husbands have reproductive health challenges in two of the five states with the highest proportion of divorce/separation in Nigeria.Four focus group discussions were conducted in two local government areas. The women were recruited from a quantitative couple-study for men with sexual health problems. Focus group responses were transcribed and analysed using systematic-content-analysis with thematic organisation of the summaries and systematic typologies of participants’ responses.The results revealed the coping strategies employed by women in this environment: seeking guidance from their religious leaders and family doctors, physical-sexual-therapy, abstinence and concubinage. The participants indicated that they encountered difficulties in discussing their husbands’ sexual health problems with a third party.The study concludes that husband’s sexual ability is crucial to the sustenance of the marital relationship. Religious leaders and family doctors often serve as mediators to husband-wife conflict management. Counselling is recommended in cases of sexual health problems. Husbands should be encouraged to seek treatment and share their sexual challenges with their spouse. The medical officers and religious leaders could also be trained in family-conflict management.The online version of this article (doi:10.1186/s12978-017-0341-2) contains supplementary material, which is available to authorized users. There are many male reproductive health challenges, such as low sexual desire, ejaculation disorders, penile disorders, impotence, and painful erections; these conditions may be associated with negative changes in intimate relationships including marital dissatisfaction and conflict. Male reproductive health challenges also include genital ulcers, testicular disorders, prostate cancer or sexually transmitted infections that could result in infertility or a breakdown of the intimate relationship. Couples facing infertility may experience shame, especially in traditional African settings where the importance of masculinity and patriarchy remain strong and childlessness is greatly stigmatized. Support for reproductive health can be critical to sustaining the marital relationship and the quality of this relationship.This study assessed the coping strategies adopted by women whose husbands have reproductive health challenges in two Nigerian states with some of the highest rate of divorce. Participants were recruited from a quantitative couple-study where their male partners experienced sexual health problems. Four focus group discussions were organised in two local government areas. Respondents were asked about their knowledge of male sexual disorders, the challenges experienced by their husbands, the support they provided, their sex life, their current level of sexual satisfaction, and the strategies used to cope with their husband’s conditions.The results of these discussions revealed that their husbands experienced a range of sexual disorders: low sexual desire, ejaculation disorder, impotence, erectile dysfunction, genital ulcers, testicular disorders and prostate cancer. It also found that participants sought guidance from community/religious leaders and family doctors, received physical-sexual-therapy, abstained from sexual relations and concubinage as strategies to cope with these conditions.The coping strategies adopted by women could be important for marriage counsellors, social workers, and medical personnel. Counselling is recommended for the management of men’s sexual health problems, especially among women as a crucial tool to reduce marital conflict. Men should also be encouraged to seek treatment and to share their sexual challenges with their partners.When the husband suffers from a sexual disease, both the marital partners are affected –3. How tMale reproductive health challenges are a range of disorders that affect the male reproductive system. These include penile disorders, erectile dysfunction, balanitis (swelling of the foreskin or penis), prostate cancer, genital ulcers, testicular disorders, low sperm count, painful or premature ejaculation, loss of libido, urethral discharge, and sexually transmitted infections –15. ThesThere has been a global increase in male sexual disorders , 23, 24,This study is anchored on the way-of-coping theory, as developed by Folkman and Lazarus in 1980s. This theory defines coping as the sum of cognitive and behavioural efforts to handle demands  which are considered taxing, demanding or problematic . In thisSome instances of male sexual dysfunction are not preventable; however, the resulting marital conflict may have solution through effective management. To date, the coping methods of marital conflict or dissatisfaction caused by husband’s sexual problems have not been explored in the literature, especially in Nigeria. This study is, therefore timely, considering the increased rate of divorce, martial conflict and their associated consequences such as multiple sexual networking, ‘concubinage’ and vulnerability to HIV/AIDS and other STIs in sub-Saharan Africa , 38, 39.This study used focus group discussions (FGD) to explore the coping strategies adopted by women whose husbands had reproductive health disorders. Focus group discussions were used to encourage interactions among participants. The focus group discussions offered the opportunity to seek clarifications, raise follow-up questions and probe for more information.Elements of framework analysis were used in data analysis. According to Ritchie and Spencer (1994) and Green and Thorogood (2004), framework analysis involves series of interconnected stages ranging from familiarisation, identifying a thematic framework, indexing, charting, mapping and interpretation , 41. In Grant No: CUCRID-RG/AMOO/PHD/2007; details also indicated at the funding section). The study was conducted in two states (Lagos and Osun), two of those with the highest rate of divorce/separation in the country  deliver you” .“Doctors are held in high esteem in our town, they are highly respected and most people have confidence in them because they are trained to keep secrets” (Woman aged 15–34).Across all discussions, seeking support from family doctors was one of the important steps in coping. Nearly all participants complained to their family doctors of the sexual health problems of their husbands. The general perception among these participants was that the medical doctors and other health personnel were . Women describing this strategy were mostly older women, and the sexual problems ranged from ejaculation problems to low sperm count. Other comments supporting this response showed that “keeping to oneself (on the issue) is the best option”. A woman (aged 40) indicated that “an issue like this is not openly discussed”, hence the need to “remain with it” (to be silent over it). However, another participant (in age 35–50) believed that “If there is a deep affection between [the] couple, come rain and the sun, they must stay together”. Almost one-quarter of all participants indicated they have been ‘holding-on to fate’ in managing these health concerns. Related to this, another woman (aged 35–50) considered a ‘silent posture’ over disagreements on sexual matters as the best option to sustain the marriage: “for me, it is the best option for me, so as to allow tension to reduce”.The results of the analysis revealed a popular coping strategy among the wives, a “resignation to fate approach”, where no effort was made to resolve the health problem, and the situation was considered closed or what they are destined to bearThe next strategy for coping with their husband’s sexual problems was to seek support from community leaders, such as religious leaders . Women in this category had husbands with libido problems and in some cases believed that their husbands’ disorders were the result of a spiritual attack. Seven of every ten participants reported seeking support from their spiritual leaders. Although, responses were not recorded by religious affiliation, remarks were made by more than half of all participants.“the fine could be anything: money, food or sacrifice”. Another woman (age 30), indicated that “it [also] depends on the ‘seriousness’ of the offence or the elders involved”. This was supported by two women (aged 35–50 years), who stated that if it is a sexual matter, the husband will be ordered to have sex with his spouse, unless the husband is impotent. Another woman (age 35–50) indicated that, “elders will know what to do”. Participants described that every decision reached by the elders must be strictly adhered to.In addition to community leaders, support was often sought from relatives. Discussions highlighted that the couple may also be invited by elders in the community. In this context, the husband or wife had the opportunity to express their grievances while the elders intervened to resolve conflict or offer advice. The participants reported that punishments were given to the erring party or the guilty party was warned. A woman, aged 47, reported that “Now tell me, what is marriage without sex? Just to sleep together or be his cook?”.The study further showed that wives adopted behavioural changes when faced with their husband’s sexual dysfunction. Results indicated that there were different strategies adopted in cases of sexual impotence; one out every five women adjusted their ‘sexual appetite’. Almost one-third of the respondents affirmed that they sought relationships outside marriage . Many could not imagine what marriage stands for without sex.Among those who adjusted their sexual behavior, were women whose husbands had sperm problems or those who could not engage in sex. The majority of women who opted for concubinage were those whose husbands had erection problems, many of them were 15–34 years. Two participants, however, believed that their situation did not warrant seeking external sexual partners. These participants believed there was hope, the condition may be temporary and, according to them, seeking help could resolve the problems.“after all, sex is not food”. These women believed the situation gave them the privilege of focusing on other family issues, friends, and their careers. Another woman (aged 35–50) responded: “we are only missing sexual closeness; we are not physically distant”. Only two respondents asserted that they adopted what can be termed “physical sexual therapy intervention” to salvage their relationships. This, according to the respondents, comprised of foreplay and creating fun with their husbands.Few women, aged 35–50, indicated that they have adopted abstinence as a solution. Three of the participating women stated that the situation gave them the opportunity to pursue businesses and work without distorting their marital relationship. These women were older and most had at least one child. Most of the women who claimed they had been abstaining from sex and those who indicated that they diverted their attention to their businesses and spiritual matters described ‘sexual intercourse as a non-primary issue’. A woman (aged 35–50) responded that you will always be feeling you are not a woman or not attractive”. While women in this group affirmed that it was negligence on the part of husband to allow such problems to progress untreated, they also indicated that “there might not be any reason to “endure agony” arising from [any] man’s negligence”. Another woman, aged 15–34, indicated that having children was crucial to marriage, and if the husband could not impregnate her, she would not hesitate to leave. An excerpt from another woman in the same age group shows: “If you want to manage it you can stay. […] If you want a child desperately, you don’t need to wait or announce your departure from his house”.Responses from younger women (aged 15–34 years) favoured separation if the problem persisted. A participant indicated that, “if your husband cannot have sex with you, “If your man is the only bread winner of the family, you would not want to divorce or leave him just because of that [sex]” .“If kids have been there before the problem comes, what do you do, would you leave your children? No, you just have to stay for the sake of your children” .Among women who preferred to stay married, they explained this choice based on the desire for children and economic reasons.“for better and for worst”.“If there is deep loving affection between couple, come rain and the sun, they stay together” .Few respondents believed that marriage becomes sacrosanct the moment it is solemnised and the party should stay together “husbands are well-respected as the head, authority over the spouse and whatever issues pertaining to them (i.e. the husband) can only be uttered by them alone”.“It is a painful situation”. “[…] It has never been a subject of open discussion since ages”..“Most men you see around have so much under their clothes, I mean, they hide so many problems to themselves”.In addition to the primary themes identified, findings indicated that wives encountered challenges in reporting or discussing their husband’s sexual problem. The majority of participants indicated that when a problem is discovered; the wife cannot easily report their concerns. The general impression was that “You remain silent over it”, “[…] it is not a subject of discussion with your neighbours”..“If the man hears you tell anyone, he might scrape off your head” .There was consensus, especially among older participants, that sexual problems cannot be easily reported, not only due to tradition, but also because of the manner the husband may interpret this act. Few of their responses are as follows:“Coping with an impotent man is dangerous; they are always nervous, worry, aggressive and ill-tempered” .A few women indicated that it is dangerous to remain married to an impotent man: “action speaks louder than voice”. Some suggestions offered by participants include, spiritual assistance, ‘mandating’ the family doctor to perform medical tests and reducing the consumption of certain food or alcohol.Participants were asked whether they had recently discussed with their husbands the need to seek a solution. Almost half of the participants affirmed they have indirectly done so stating that This study provides evidence of coping strategies used by women whose husbands have sexual health problems. These findings extend beyond existing studies on husband-wife communication and wives coping with alcoholic spouses –7 or sexAmong the important contributions of this study, is the development of a thematic framework demonstrating the coping strategies of women with husbands that have reproductive health problems. Several of the primary themes suggested that the conjugal relationship could be sustained in spite of these sexual health problems. It also highlighted that rather than resigning to fate alone, seeking guidance from health practitioners, especially family doctors and discussion between the spouses (husband-wife communication) could help. This finding is in concordance with coping mechanisms that suggest that appropriate responses could deal with external stressors in a manner to avoid conflict , 33, 35.The patterns of responses indicated two groups: (1) situations in which women may separate, divorce or engage in concubinage, and (2) situations in which women would endure sexual problems and maintain the marriage. The majority in the first group had husbands with erectile problem or suffered from premature ejaculation. Women in the second group had children and husbands with genital ulcers or testicular cancer. The second group also included women whose husbands were the breadwinners, women that resigned to fate or believed there was hope for the problem to be solved. The finding that women might not want to divorce or separate if children are involved, is similar to findings from Botha and Booysen (2012) and D’Souza, Karkada, Somayaji & Venkatesaperumal (2013). If the couple already had children, the wife might consider the future challenges children would face if they divorced , 28. ManA number of participants opted for separation or sexual relationships outside the marriage which may increase transmission of HIV/AIDS and other sexual transmitted infections , 39. SinThere are limitations of this study, which include the use of a convenience sample of health facilities which limits generalizability of the findings. The sexual health problems were self-reported and were not confirmed through medical testing. The small number of FGDs could also be a limitation to the scope of the study. Finally, the combination of all male sexual health problems together may hide the variations inherent in different sexual challenges. This study only established responses by husband’s reproductive health problems and ages, other characteristics such as year of marriage were not collected.This study has added to the body of knowledge on coping strategies for sexual challenges. This study concludes that husband’s sexual health is crucial to the sustenance of the marital relationship and that religious leaders, as well as family doctors, may be indispensable mediators in husband-wife conflict management. However, the fact that the wives cannot easily discuss or report sexual health dysfunctions can be an obstacle to a healthy relationship. This work is essential for planning couple sexual health services in Nigeria, and where appropriate, couples should be encouraged to attend clinic together for counselling and treatment. Counselling on the management of men’s sexual health problems, especially among the wives, is recommended. Men should also be encouraged to seek treatment and share their sexual challenges with their partners (Additional file


In clinical practice, diagnostic hysteroscopy (DH) videos are recorded in full which are stored in long-term video libraries for later inspection of previous diagnosis, research and training, and as an evidence for patients’ complaints. However, a limited number of frames are required for actual diagnosis, which can be extracted using video summarization (VS). Unfortunately, the general-purpose VS methods are not much effective for DH videos due to their significant level of similarity in terms of color and texture, unedited contents, and lack of shot boundaries. Therefore, in this paper, we investigate visual saliency models for effective abstraction of DH videos by extracting the diagnostically important frames. The objective of this study is to analyze the performance of various visual saliency models with consideration of domain knowledge and nominate the best saliency model for DH video summarization in healthcare systems. Our experimental results indicate that a hybrid saliency model, comprising of motion, contrast, texture, and curvature saliency, is the more suitable saliency model for summarization of DH videos in terms of extracted keyframes and accuracy. The recent advancement in modern technology has shown promising results in human reproductive healthcare. One of the popular method of ensuring reproductive health is diagnostic hysteroscopy (DH), where the sensitive regions of female reproductive system (FRS) are assessed and visualized to diagnose uterine abnormalities  for the frame “DHF”. “l” refers to the scale of contrast and “N(p)” shows the neighborhood of the pixel “P”, which is 5 × 5. The value of ɳ is set to 3, indicating the levels of Gaussian pyramid (Liu et al. Contrast map is an effective measurement for finding the uniqueness of a region in a video frame, which has been widely used in computer vision algorithms (Ejaz et al. During DH examination, the gynecologists move the hysteroscope with a certain orientation to effectively visualize the areas of interests. The previously mentioned saliency detection models are less effective in handling DH frames with such abnormalities. In this context, curvature map is comparatively more effective due to its rotational-invariant property in finding the keyframes with abnormalities, which are captured from different orientations. Furthermore, the neuroscience and psychophysical research also dictates that curvature is an important factor in determining the saliency and improving the decision of gynecologists in selection of keyframes. The curvature map “CM” for a DH frame “DHF” can be calculated using Eqs. After computing the numerous saliencies for each frame, it is important to combine them to generate a fused saliency map for keyframes extraction. There are several ways to fuse the different saliencies such as linear fusion, linear weighted fusion, max fusion, and non-linear weighted fusion (Ejaz et al. After calculating the attention curve, the user/gynecologist is asked to specify the number of keyframes “NKF” for a given DH video. Accordingly, the video is divided into “NKF” number of shots. Within each shot, the frame with highest saliency score is determined as keyframe. By only changing the value of “NKF”, a different set of keyframes can be extracted, enabling gynecologists to analyze the DH video at different summarization levels.This sub-section illustrates the performance evaluation of various saliency detection models and general-purpose VS methods for DH videos abstraction. Experiments were performed on a set of DH videos according to Ejaz et al. , each ofTable Table Figure The general-purpose video summarization schemes are less suitable for hysteroscopic videos due to their significant similarity in color and texture, and absence of shot boundaries.Among the evaluated visual saliency models, a hybrid saliency detection model comprising of motion, texture, multi-scale contrast, and curvature is found as the best combination of visual saliencies for hysteroscopic video abstraction, considering its accuracy and extracted keyframes.During the process of diagnostic hysteroscopy, several hysteroscopic sessions are conducted for a single patient per day. Due to the large number of patients and their multiple hysteroscopic sessions, an enormous amount of hysteroscopic videos are collected. However, a limited number of frames are required for actual diagnosis process, whose manual extraction by gynecologists is comparatively difficult and time consuming due to large-sized hysteroscopic videos. To facilitate the gynecologists in browsing for desired diagnostically important contents, video summarization schemes are used. In this work, we have conducted a comprehensive study of numerous generic and domain-specific video summarization schemes for hysteroscopic videos. Further, we have investigated the performance of various visual attention models combined with domain knowledge for summarization of DH videos. Our findings based on numerous experiments are reported as follows:In future, we have intension to focus on minimizing the computational complexity of the system by extracting light-weight features from DH videos. Another possible future direction is to combine data hiding [watermarking (Liu et al.