In order to meet the challenges of caring for an injured person, caregivers need access to health information. However, caregivers often feel that they lack adequate information. Previous studies of caregivers have primarily focused on either their time and emotional burdens or their health outcomes, but the information needs of caregivers have not been thoroughly investigated.The purpose of this investigation was to identify the preferred sources of health information for caregivers supporting individuals with injuries and to explore how access to this information could be improved.A total of 32 caregivers participated in semistructured interviews, which were used in order to develop a more in-depth understanding of these caregivers’ information needs. Digital audio recordings of the interviews were used for analysis purposes. These audio recordings were analyzed using a thematic analysis or qualitative content analysis. All of participant’s interviews were then coded using the qualitative analysis program, Nvivo 10 for Mac .The caregivers endorsed similar behaviors and preferences when seeking and accessing health information. Medical professionals were the preferred source of information, while ease of access made the Internet the most common avenue to obtain information. The challenges faced by participants were frequently a result of limited support. In describing an ideal health system, participants expressed interest in a comprehensive care website offering support network resources, instructive services about the injury and caregiving, and injury-specific materials.According to the participants, an ideal health information system would include a comprehensive care website that offered supportive network resources, instructive services about the injury and caregiving, and materials specific to the type of patient injury. More than 52 million US residents act as a caregiver to an adult aged 18 years or older . The carCaregivers assume responsibilities that affect their personal lives, financial status, and mental well-being . They ofMany caregivers experience unmet support needs, including insufficient care-related information, unsatisfactory emotional support, and difficulty maintaining relationships -15. The In order to meet the challenges of caring for an injured person, caregivers need access to health information. However, caregivers often feel that they lack adequate information and support ,14. PrevHealth information is critical for caregivers to provide the most effective care for the patients . Family TBI, SCI, and burn injuries are prevalent throughout the United States and are severe in nature -24. AccoSubjects were recruited through a number of different outreach methods. First, National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR)–funded SCI, TBI, and Burn Model Systems grantees were contacted to recruit participants. The grantees were asked to identify potential participants and direct candidates to the recruitment website. Subjects were also solicited through advertisements placed in printed materials, websites, as well as social media sites. Finally, participants were reached by sending recruitment emails provided by TBI, SCI, and burn consumer advocacy groups.Subjects were selected to participate if they self-identified as the primary caregiver of a person with either a TBI, SCI, or burn injury. The number of hours per week spent on caregiving was not an inclusion/exclusion criterion. All caregivers needed to be at least 18 years of age and could care for a recipient of any age. Informed consent was obtained  from all of the participants and assurances of anonymity/confidentiality given. Participant distress and safeguarding protocols were established. The Institutional Review Boards of both the American Institutes of Research and George Mason University approved this investigation.Semistructured interviews were used in order to develop a more in-depth understanding of caregivers’ information needs. A psychologist (AAW) trained all interviewers on the proper techniques in conducting semistructured interviews. These trained interviewers were an occupational therapist and Masters of Public Health graduate students. The interview consisted of three sections. In the first section of the interview, caregivers were asked to discuss the subject’s care background as well as the activities of daily living and instrumental activities of daily living of the person receiving care. The second section used a questionnaire to assess the various types of needs caregivers may have. The final open-ended section of the interview examined the individual’s medical, rehabilitation, and continuing care experience, specifically focusing on information needs assessment . For thiThinking back over the time since the injury, what has been most difficult for you?What has been the most helpful for you since the injury?We had discussed your health earlier in the interview, and I was wondering if you feel that your health has changed since becoming a caregiver?Now, we are going to spend some time focusing on the informational component of your life as a caregiver. So, how do you currently receive information related to ?When you do receive or access information, how, if at all, do you use the information?Has the information that you received or accessed been useful? Pertinent to your needs? Accurate? Understandable? Trustworthy?What are the biggest difficulties you face in accessing the kind of information you want about the patient’s (or loved one if appropriate) condition?I want you to imagine that we can start from scratch and develop a new approach for getting information to caregivers. In your dream world, what would this new model look like? Don’t worry about the money required, or whether your idea is logistically feasible.Digital audio recordings of the interviews were used for analysis purposes. These audio recordings were analyzed using the framework approach . This apAll of participant’s interviews were then coded using Nvivo. In some cases, a participant would respond to a question in a way that fell beyond the scope of the developed coding system. In those cases, a new code was added and the remaining research team members were notified of the change. In total, 5 codes were modified during the coding process.The coding system was then used to develop an analytical framework. The codes were grouped together into categories. In order to facilitate this process, the tree map feature was used to visually represent potential categories. The researchers then defined these groupings of codes. The last step was the interpretation of the data. The researchers met many times to discuss the characteristics of and differences between the data.A total of 40 caregivers provided consent and were interviewed. However, 8 of the interview audio files were unable to be read by the Nvivo program. Thus, the analysis was based on the remaining 32 caregiver interviews, of which 16 providing care to a person with a TBI, 10 providing care to a person with a SCI, and 6 providing care to a person with a burn injury. The open-ended response section of interviews lasted 34 min on average, ranging from 12 min to 115 min.Study participants had provided care for 7.0 years (SD 8.4) on average. Details of the study population’s ethnicity, socioeconomic status, and injury type can be found in The majority of subjects (n=30) received injury-related information via the Internet. The most common ways caregivers accessed Web-based information was through sites found using search engines (n=20) and medical websites (n=20). Not all types of Internet resources were widely used; a smaller proportion of caregivers visited government (n=10), support group (n=9), or discussion board (n=5) websites regularly.Caregivers described difficulties that interfered with their ability to access information about treatment, caregiving, and health conditions. When asked to describe their greatest obstacle to accessing information, caregivers most commonly cited challenges simply finding information (n=10), followed by medical/insurance bureaucracy (n=9), unsupportive medical staff (n=7), and lack of support from sources other than medical staff (n=4). The majority of caregivers (n=28) believed that “access to the Internet” did not hinder their ability to access health information. Similarly, difficulty in finding “culturally appropriate” information did not hinder access (n=26). In contrast, caregivers believed that the “accessibility to information (other than the Internet)” (n=15), “time to search” (n=14), the “understandability of information” (n=12), and obtaining “credible information” (n=10) at least partially interfered with their ability to access to injury-related information. Only 8 caregivers indicated that they did not face any difficulties when accessing information. However, finding concrete information still proved to be a challenging task due to the inaccessibility of specialized care or gaps in medical research.There are just so few people that are knowledgeable in our area, and probably in most geographic areas, about the specialized needs of people with spinal cord injury; especially quadriplegics. There are so many systems of the body affected and there aren’t too many  in any one given area who really understand all the ramifications of how the injury’s affecting all the body systems.Interview 2003; SCII think just finding  was the biggest challenge. There’s not a lot known about burns, relatively speaking. There’s a lot of anecdotal stuff from survivors but there’s not a lot publishedresearch on burns and burn recovery.Interview 1002; burnWe’ve chosen doctors who are, who will listen. Who are open to, if they don’t know the answer, taking what we say, and checking it. But last time we looked for a doctor, I actually went and interviewed doctors...because there aren’t a lot of people that know about (patient’s) exact condition.Interview 2011; SCIThemes surrounding the process of gaining health information emerged seeking different types of information, utilizing multiple sources, and making comparisons. The process of locating information involved extensive preparation, persistence, and due diligence.Although there were differences in the types of health information individual caregivers sought, common themes emerged. Caregivers researched information that was directly related to supporting the individual receiving care. “Treatment” (n=14), “rehabilitation” (n=13), and “medication” (n=11) emerged as dominant themes. Due to the inherent chronicity of these serious injuries, many caregivers sought information on “long-term care” (n=15), that is, research on the long-term effects of patient conditions and sequela, and adjustments to disabilities.For caregivers, an important source of health information was seeking information through individuals who had similar experiences. These opportunities for seeking information could be from various outlets including organized support groups designed to share experiences with those in similar situations, informal sharing, development of coping strategies with professional counselors, doctor relationships, or rehabilitation settings with clinical specialists and organizations centered on TBI, SCI, or burn survivors.When I have actually sought counseling...about... trying to adapt and cope with this kind of new person that I’m dealing with. That’s been very helpful to me to have some support person that I can call.Interview 2009; SCIwe call it the working support group, because it was headed by a neuropsychologist, and he would actually have the survivors worktrying to improve themselves. So that has been very useful. The support group that we go to here in our town is more of a social kind of thingInterview 3015; TBICaregivers utilized a number of different sources to acquire health information. Common sources included “Web-based research” (n=26), “doctor instructions” (n=16), “medical journals” (n=14), and “injury organizations” (n=13). Web-based communication, library visits, clinical trials, and other persons with similar injury experiences were referenced, albeit less frequently. Caregivers often compared information from multiple sources (n=21) to evaluate its quality and corroborate its accuracy.I spent a lot of time, really the first 4 monthsdoing PubMed searches, and reading literature, and reading textbooks on burns, and all that kind of stuff. That was really the first thing I did, was kind of educate myself about burn and the burn process and recovery and healing.Interview 1008; burnEverything and anything I could get my hands on to understand (the injury). I have visited WebMD, the traumatic brain injury model centers...the National Traumatic Brain Injury Association. I’ve been out there on all the websites.Interview 3001; TBIPersonal experience dealing with an injury also served as a reference point for caregivers. Caregivers retrospectively compared their patient’s outcomes with Web-based information they received, enabling them to determine its usefulness, accuracy, and understandability. However, the caregivers faced a steep learning curve when acclimating themselves with injury-related health information early in their transition to a caregiver role.When I did read about the burns and different things like that, we may not have been at the stage that it talked about, but we did get there. And I could remember times where it was like “oh, that is what they said was going to happen.”Interview 1004; burnI did understand it, but after, going, advocating and learning more, and then going back to some of the older documents that I had researched, and rereading it, I understood it more, because I guess I had actually experienced some of it.Interview 3001; TBIKnowledge of various treatment options also influences caregiver actions and their respective patient’s rehabilitative outcomes. Caregivers reported instances of reliance on their own judgment based on independent research. This sometimes led to negotiation or collaboration with medical professionals....there’s very little research on the subject, but there’s some, about the link between things like fish oil and brain injury. And, I had to try that, and noticed a really big improvement in both areas, in terms of clarity of thinking and his skin condition. It’s anecdotal, I have no proof, but I really feel like it’s made a difference. It’s not something I would have considered without looking at websites.Interview 3003; TBIa few years ago I said to his physician, shouldn’t he be tested for osteoporosisI had learned online that quads are at high-risk for osteoporosis. So he agreed to test him, and did test him, and indeed he did have osteoporosis.Interview 2011; SCIIf we’re talking about medications or treatments, or, you know things that I may have read about but no one has suggested. So I kind of throw that out there like neurofeedback, you know, as something that I ran across, you know on the Internet, and benefits for survivors of traumatic brain injury. And so I brought that up to one of his neuropsychologists and we have adopted...getting him involved with neurofeedback.Interview 3017; TBIThe final open-ended interview question asked participants to describe their ideal system for getting health information to caregivers without having to consider practical limitations such as cost. In doing so, respondents offered a variety of potential modifications to health information systems that they felt would be beneficial to caregivers. In conceptualizing model systems, participants often focused on health information, support services, and modes of delivery most applicable to them. As a result, responses diverged from one another, but maintained commonalities in information sought, types of services, and access to information.Support network information (n=26) was the most common response, though again employing a multitudinous definition of support, including organized support groups, information for and from people with shared experiences, resources to access services related to rehabilitation, ongoing care, and daily living.I would want the information probably right after whatever had happened and I wouldwant some positive reinforcement, and just general information, and maybe somesupport right off the bat from other people; other people that have gone through thiswho have experienced the same thing. And it needs to be positive interaction, not negative.Interview 3009; TBICaregivers also expressed a desire for access to updated publications (n=11) as a method of staying well-informed with current research. Guides covering treatment, recovery, and rehabilitation, via the Internet (n=5) or in hard-copy form (n=9), were suggested as well. Those guides would serve as an educational tool to help prepare caregivers and thus mitigate their risk of feeling overwhelmed following the injury event.I think it would be great to have a manual on burn injury and recovery that is categorized by subject matter and is in both print and online form and easily available to all patients and family members. That has put together in one place, all known and accurate current research and has weeded out anything that has either old and has been proven inaccurate, or irrelevant, or whatever. So it’s done all the librarian work for us, so that we have it all in one place.Interview 1002; burnThere’s no good, central clearinghouse. It’d be great if there was one place on the Web you could go that had links to all these places. That had the government links, that had care-cure forums, that had Avery biomedical, every place that, that can help you. Every place that can help you, like with durable medical supplies, a place that can help you with...hooking up with caregivers. Places that could help you connect with other people in your situation.Interview 2011; SCIAs respondents discussed the services that they believed should be available in a model health system, two themes emerged. The first was caregiver support services. Specifically, resources such as “support groups” (n=22), “care coordinators” (n=15), “caregiver training” (n=14), and “classes on injury condition, treatment, and life” (n=14) were frequently suggested to prepare caregivers and their families for the rigors of caring for someone with TBI, SCI, or burn.Everybody needs to be professionally trainedwhether it be education, legal, medical, or whatever, that the proper people are trained and are able to explain, or tell the caregivers and the survivor, what to expect, where they can go, and so forth. So I think the training is very much needed.Interview 3001; TBISeveral respondents recommended support group sessions with people that had similar experiences for patients and their caregivers, while they are still in the hospital.A support group led by a professional, but run by, and taken over by the people who are the caregivers, or the family membersthe one paid person would actually get the real information and give it to the family members, and the family members in turn could be providing things that they learned, which in turn could be coordinated and disseminated as information.Interview 2010; SCII wish there was somebody like myselfthat could come into a burn survivor and their family’s room and make that connection and answer their personal questionsif I would have had somebody like me or my other SOAR (Survivors Offering Assistance in Recovery) volunteer members come into my room, even that first week, I feel like my life would have been so much easier. I felt so lost.Interview 3016; burnThe second theme that emerged was medical care services. Respondents expressed their desire for “rehabilitation services” (n=19), “medical specialists” (n=13), and “financial services” (n=6). In many cases, respondents expressed their desire for their local health care provider to recreate the services offered at state-of-the-art facilities. Physical access to specialized treatment facilities can be a substantial barrier; therefore, caregivers prioritized proximity and transportation to health care facilities.Caregivers most frequently recommended that an ideal health information system be accessed through in-person communication (n=20) or via the Internet (n=18). A combination of these two methods, such as a “livechat” feature (n=7), was cited to allow for interactive question and answer sessions. Printed materials (n=9), phone systems (n=8), and television programs (n=3) were also recommended as resources for sharing information or to serve as learning materials for caregivers. In the context of comprehensive Web-based information, the user-friendliness of the Web page and an effective search function emerged as critical features.At least if you have that human, that person-to-person dialogue going, you can sometimes get answers to things that are specific to your own situation, instead of reading through a Q&A or something that’s posted.Interview 1004; burnThe Internet, of course, is the easiest and fastest way for me to get information besides talking to actual doctors in the hospital.Interview 3001; TBIIt would be nice if there was a hotline you could call if you were in a situation where you needed somebody to talk to right away. There are a lot of urgent situations when you are dealing with disability and I wish there was some kind of caregiver hotline that would not only support you emotionally, but maybe help alleviate some of the stress when you feel like you’re dealing with something completely alone. Interview 2003; SCIThis study offers insights into the challenges faced by individuals caring for persons with TBI, SCI, and burn injuries. Participants revealed the obstacles that they faced, including gaps in formal and informal support systems, emotional strain, and a limited ability to access health services and health information resources. The interviews further revealed patterns and preferences for seeking health information among those caring for individuals with TBI, SCI, and burn injuries.Although previous research has examined the burden experienced by individuals caring for elderly persons or degenerative conditions associated with aging, such as dementia, relatively few studies have compared the burden experienced by those caring for life-long injuries. This study finds that medical professionals are the preferred method of receiving health information among TBI, SCI, and burn caregivers, similar to the preference of those caring for other conditions . NeverthWhen TBI, SCI, and burn caregivers sought health information, it was commonly related to medical care for the injured person. Caregivers are often required to perform medical tasks despite rarely having clinical training ,18. ThisThe obstacles and preferences that caregivers discussed indicate a pronounced need for access to Web-based resources that provide synthesized care information and access to support resources. Features that combine the utility of the Internet with the expertise of medical professionals, including care-support hotlines, have been shown to reduce caregiver burden and therefore may improve their ability to provide care . Thus, uThe in-depth, semistructured interviews allowed each participant to provide thorough insights into the health information issues related to their experience. Common experiences emerged, denoting the transferability of responses. Still, there were limitations. This study focused on individual interviews. A focus group study involving caregivers of individuals with these injury types may provide additional information because of the group interaction that is inherent in focus groups. Given the retrospective nature of the questions, there is a risk of recall bias from participants. In addition, this study had a small sample size and an uneven distribution of caregivers for each injury type. Study participants were predominantly recruited using the Internet which may have biased our sample in terms of preferences for Internet resources. The number of caregivers for each injury type was different, impacting the relative weight of responses from each study participant. Due to technical limitations, eight of the interview audio files had to be excluded from analysis. Caregivers were not asked if they were the only individuals who were caring for the recipient, which could have impacted their information needs.The codebook itself could have been simplified by combining codes. Interrater reliability measures, percentage agreement, and kappa coefficient, indicated that both coders applied codes consistently, most likely due to the shared creation of the codebook, and follow-ups on interpretation of each code. However, IRR was not 100%, therefore minor discrepancies in code placement may be assumed.The detailed interviews conducted with TBI, SCI, and burn caregivers revealed the methods and resources that were used to acquire health information. Medical professionals were the preferred source of information, while ease of access made the Internet the most common. The challenges faced by participants were frequently a result of limited professional and social support. In describing an ideal health system, study participants expressed interest in a comprehensive care website that offered support network resources, instructive services about the injury and caregiving, and materials specific to their injury. An ideal health information system should incorporate methods of communicating directly with health professionals.


With this informal guide, we try to assist both new and experienced phage researchers through two important stages that follow phage discovery; that is, naming and classification. Providing an appropriate name for a bacteriophage is not as trivial as it sounds, and the effects might be long-lasting in databases and in official taxon names. Phage classification is the responsibility of the Bacterial and Archaeal Viruses Subcommittee (BAVS) of the International Committee on the Taxonomy of Viruses (ICTV). While the BAVS aims at providing a holistic approach to phage taxonomy, for individual researchers who have isolated and sequenced a new phage, this can be a little overwhelming. We are now providing these researchers with an informal guide to phage naming and classification, taking a “bottom-up” approach from the phage isolate level.  Virus taxonomy is currently the responsibility of the International Committee on the Taxonomy of Viruses , which Bacterial virus taxonomy has undergone a number of changes since the discovery of bacteriophages in the early 20th century. Electron microscopy—which led to the recognition of different phage morphologies—and nucleic acid content provided the basis for the first classification scheme ,4. SinceMyoviridae, Podoviridae, and Siphoviridae [For many years, the grouping of prokaryotic viruses in lower rank taxa such as genus and subfamily happened at a minimal pace. Taking the tailed phage families as an example, the 5th Report of ICTV (1991) described one genus in each of the families oviridae  and 18 goviridae . As nuclThe availability of genome sequence data also gave rise to a range of potential classification or grouping schemes, such as the Phage Proteomic Tree , phage nIn this paper, we provide a naming and classification guide for researchers who have isolated and sequenced a novel bacteriophage isolate specifically; however, these guidelines can also be applied to archaeal viruses. The guide will follow a “bottom-up” approach , rather than the “top-down” approach which was used in the past to assign isolates to a family based on morphology.You have just isolated and sequenced a bacteriophage, so what do you do next? Well, hopefully, you plan on publishing your finding and submitting the sequence to one of the public databases that are part of the International Nucleotide Sequence Database Consortium (INSDC), GenBank, the European Nucleotide Archive (ENA) or the DNA Data Bank of Japan (DDBJ) . That isPerhaps the most important rule of bacteriophage naming is “do not use an existing name.” There are already four dissimilar bacteriophages named N4, making it very difficult to distinguish between them. So before naming your bacteriophage—and definitely before publishing a report on it—please take the time to compare proposed names against those already used within the field. A good—if not dated—place to start is Bacteriophage Names 2000  or its rvirus of Bacteria, infecting Escherichiacoli, with myovirus morphology, named VR20. In this case, the latter part of the name (VR20) will be the phage’s common name—you can refer to the phage as VR20 in your paper—and the BAVS will only use this part when naming a taxon .Staphylococcus aureus DSM 1234. This approach to species naming was officially adopted by the BAVS in 2015 and should also be used in isolate names [Use only the isolation host genus in the name, rather than higher order taxa names—such as Enterobacteria, Pseudomonad, or the generic Bacteriophage—or lower order taxa names like te names .Do not combine the host genus and the word “phage” into a single word, for example, Mycobacteriophage, Mycophage, etc.Do not use an existing unique identifier in the name.Do not use Greek letters in the unique identifier.Do not start the unique identifier with a numeral and do not use only use only a single letter. Identifiers should include enough complexity to easily distinguish your bacteriophage from others.Do not use hyphens, slashes, or any type of special character . You may use underscores to separate parts of the designation , but these underscores cannot be carried over into official taxon names see .Do not use controversial names/phrases, profanity, names of prominent people, and trademarked names/phrases as unique identifiers.Please do contact the friendly folks on the BAVS if you have any questions.Please use the following bacteriophage naming guidelines:As a caveat to these guidelines, we would like to launch a plea for accuracy and precision in the use and referencing of existing phage names. For example, Salmonella phage Felix O1 has been cited as Felix-O1, FelixO1, Felix 01, and Felix-01. These inconsistencies cause confusion within the community and must be avoided.Escherichia virus T4. Higher order taxa names are derived from unique identifiers used in isolate names as in the genus T4virus. Sometimes these unique identifiers are too similar to existing taxon names, inappropriate, or do not otherwise conform to ICTV taxa naming standards, and a different taxon name must be chosen.The rules for naming taxa are described in the International Code of Virus Classification and Nomenclature . TypicalOnce you have isolated, sequenced, and named your new bacteriophage, it is time to start thinking about sharing your data with the world. Today, sharing your results is not simply about publishing in a peer-reviewed journal. While such descriptions are central to the scientific process, so, too, is the sequence of your new bacteriophage. Though often overlooked, submitting your new bacteriophage sequence to a public INSDC database such as GenBank is critical to making your sequence publically available for generations to come. Please keep in mind that in this age of bioinformatics and computational biology, it is likely that over time the sequence record for your new bacteriophage will be accessed exponentially more often than a traditional publication. In other words, do your best to provide detailed and accurate information about your phage when you submit the sequence to an INSDC database. This includes providing the most accurate classification data possible.Escherichia virus T4, provide the name of your new virus, e.g., “Escherichia phage My_New_Virus,” and the lineage “Viruses; dsDNA viruses, no RNA stage; Caudovirales; Myoviridae; Tevenvirinae; T4virus; Escherichia virus T4”. In cases where your new phage cannot be placed in an existing species, provide a lineage that reflects classification. For example, if your new phage belongs to the genus T4virus, provide the lineage “Viruses; dsDNA viruses, no RNA stage; Caudovirales; Myoviridae; Tevenvirinae; T4virus”.If known, lineage information should be included in INSDC sequence submissions using the “lineage” field or in a source note. For example, if you have sequenced a new phage that belongs to the species Do include lineage information for all submitted sequences. Even if your bacteriophage is novel and does not belong to a described species, provide the most accurate lineage information possible that places the sequence including genus and/or family using the criteria discussed in this manuscript.Do include accurate genomic composition information when no other lineage information is available or can be inferred. In most cases, it should be possible to place a new isolate within the higher-order dsDNA, ssDNA, dsRNA, or ssRNA lineage groupings.Do identify prophages using the “proviral” location descriptor.If you have questions about sequence submission to INSDC databases, please see The GenBank Submissions Handbook .If you still have questions, contact GenBank or another INSDC database.Please use the following guidelines when submitting to public databases:So why does taxonomy even matter? Well, taxonomy offers a very useful way of aggregating genome sequence data around a collection of genetic and/or molecular attributes. In this way, rules describing taxa are effectively search terms that allow you to retrieve a set of sequences with similar characteristics. Taxonomy also provides context to sequences when searching for sequence similarities. Knowing that a newly sequenced virus is highly similar to a previously classified one immediately tells you something about the new virus—the expected gene content, host range, environmental niche, etc.Bacteriophage classification also supports the organization of genome sequence data within public databases. Each viral species is represented in by at least one “reference” genome in the NCBI Viral Refseq database. Other validated genomes belonging to the same species will be stored as so-called “genome neighbors” of the RefSeq genome ,28. ThisThe first question you need to answer is basic one: “Does my newly sequenced phage belong to an existing species?” The main species demarcation criterion for bacterial and archaeal viruses is currently set at a genome sequence identity of 95%, meaning that two viruses belonging to the same species differ from each other by less than 5% at the nucleotide level. This can be calculated by comparing your sequence to existing phage genomes. There are several tools to do this , which is distinct from viruses of other genera. For each genus, defining characteristics can be determined, such as average genome length, average number of coding sequences, percentage of shared coding sequences, average number of tRNAs, and the presence of certain signature genes in member viruses. The latter can in turn be used for phylogenetic analysis with other bacterial or archaeal viruses encoding this gene to find monophyletic groups as well as higher order relationships.All the genera currently in the ICTV database have a taxonomy history (TaxoProp) accessible through the website, which can be used for researchers to assess the genus inclusion criteria. If your phage falls into an existing genus, the BAVS will define the new viral species within the existing genus. If the phage is sufficiently different from existing isolates, we can define a new genus, according to the characteristics described above. The minimum requirements for the creation of a new genus are the description of the average genome characteristics of its proposed members , a nucleotide identity comparison with visualization, a comparison of the predicted proteomes, and phylogenetic analysis of at least one conserved gene—all of these with the appropriate outliers to demonstrate cohesiveness of the new genus. While you can propose a new genus and species based upon a unique virus, the BAVS generally recommends that genera be established when two or more related viruses have been deposited in one of the INSDC databases.Podoviridae. This means that for proper classification, electron micrographs of the viral particles should be taken. Based on the morphology and the genomic information necessary for classification in species and genus, we can now determine whether your isolate falls in an existing subfamily of viruses. If your new phage, in its newly created genus, is genomically or proteomically similar to phages in an existing subfamily, the genus can be added to the subfamily. The criteria for inclusion can vary between subfamilies, and should be consulted from the TaxoProps describing the respective subfamily. In the current taxonomy releases, bacterial and archaeal viruses are classified at the family rank according to the morphology of their virions; for example, phages with short tails are placed in the family Podoviridae, the subfamily Autographivirinae groups all podoviruses that contain an RNA polymerase gene in their genome [At this time, subfamilies are only created when they add necessary hierarchical information (ICVCN Rule 3.2). In practical terms, this mean that a new subfamily is created when two or more genera show an obvious relation which is not adequately described at the family level. For instance, in the family r genome . The reqMyoviridae, Siphoviridae, and Podoviridae have become an artificial “ceiling” prohibiting the accurate description and grouping of the genomic diversity present among their member phages. For example, T4-related phages, infecting a wide range of host bacteria from different phyla, are characterized by the presence of a set of 30 conserved (core) proteins [Myoviridae, but have the genomic diversity to represent a new order. Another example involves the “lambdoid phages”, comprising both siphoviruses (Escherichia phage Lambda) and podoviruses , which cannot be grouped together in the same family at this time. The BAVS is therefore working on a new system that would abolish these families in favor of genome/proteome-based family descriptions.In a genome-based taxonomy, the tailed phage families proteins , but alsproteins . These pIn the very special circumstance that your new phage does not fit in with any known bacterial or archaeal virus, genomically or morphologically, it is the first representative of a new family. In this case, we strongly urge you to contact the BAVS Chair or the chair of an appropriate Study Group to work together to define the demarcation criteria for this new family.Nucleotide sequence comparison: NCBI BLASTn , GegeneeComparison of protein groups, predicted proteomes, identification of signature genes: CoreGenes 3.5 ,37, RoarMultiple alignment and/or phylogenetic analyses: Clustal Omega , MUSCLE Visualization: progressiveMAUVE , EasyfigThis is a non-exhaustive list with suggested software to use. The BAVS as a subcommittee is not associated with the developers of the software described below.Bacteriophage genomics, ecology, and evolution are quickly growing fields, and large numbers of new phages are being discovered, named, sequenced, and deposited into public databases. This poses semantic, logistical, and taxonomical challenges that we have tried to address in this informal guide. It is also important to understand that taxonomy is ever changing because of the unremitting flow of new information. The effort of classification is currently undertaken by a small group of dedicated scientists, but with input from the larger phage community—this means you, dear reader—we can increase the effort while keeping it manageable for each individual researcher.


We address the question “does digital epidemiology represent an epistemic shift in infectious disease epidemiology” from a statistician’s viewpoint. Our main argument is that infectious disease epidemiology has not changed fundamentally as it always has been data-driven. However, as the data aspect has become more prominent, we discuss the statistical toolbox of the modern epidemiologist and argue that problem solving in the digital age, more than ever requires an interdisciplinary quantitative approach. As a modern epidemiologist it is worthwhile to know these extensions and the situations where they are helpful, e.g., when many food items are analytically investigated by case-control studies during foodborne outbreaks.Terms like “machine learning”, “predictive modelling” and “big data” sound auspicious – in particular if they are accompanied by a promise to solve highly complex epidemiological problems. For a statistician, however, the terms are marketing jargon referring to statistical methods for high-dimensional data analysis covered in any modern text book, e.g., Efron and Hastie . In otheA further important aspect in the transition of epidemiology is that programming and data handling skills have become more essential, in particular when one needs to deviate from standard analysis. This includes the need to reshape large amounts of data, organize data beyond the flat table format, perform natural language processing on unstructed text or create visualizations of multidimensional data as a means of communicating insights. All these tasks go beyond what the average epidemiologist can achieve by manual steps with familiar spreadsheet software. Concurrently, the academic community has started to support its methodological developments by directly providing collaborative open-source software tools implementing the methods, e.g., the modelling and visualization of incidence time series, outbreak detection as well as the estimation of the basic reproduction number during outbreaks . Even meAt present, this digital transition of epidemiology is often not mirrored by a shift of content in education programmes. As an example, the European Programme for Intervention Epidemiology Training (EPIET), educating the new generation of infectious disease epidemiologists in Europe, contains only a small section on data analysis and statistical methods. Visualization, data management and programming skills are essentially left to learning-by-doing. Other aspects, such as software enhanced collaborative analyses (e.g. by revision control), quality assurance as well as reproducibility of analyses remains unknown territory.The need of epidemiologists to simultaneously possess medical and microbiologic insights as well as analytic skills, knowledge on policy development, communication and cultural competency, financial planning and management skills  underlinThe above represented a statistician’s perspective on infectious disease epidemiology in a digital age. Issues about representativeness and uncertainty remain crucial especially in the world of big data. All of this is not new, but statisticians do have useful answers to these problems – there is no need to reinvent statistics. The traditional shoe-leather epidemiology remains fundamental, but it is only efficient in a digital world, if supported by a strong analytic back-office.1 In what follows we interpret–given the context of the DELSI symposium–digital epidemiology exclusively as digital infectious disease epidemiology.


For many decades, medical educators have been struggling with assessment, as illustrated by the predominance of assessment in medical education research as well as the ongoing profound and sometimes heated discussions about how to best assess trainees’ competence and development –3. In anThe rise of outcome-based models of education and increasing pressures for educational and professional accountability resulted in a growing emphasis on assessments that provide more direct evidence of the ultimate proficiencies of interest, i. e. performance in practice. As a consequence, medical education has witnessed radical changes in assessment approaches, including development and implementation of competency frameworks and, more recently, the concept of Entrustable Professional Activities (EPAs). In workaday reality of medical training EPAs, trust and entrustment seem to emerge as concepts that are more intuitive and meaningful than competencies. They are readily embraced by clinicians and medical educators as well, suggesting we may finally have found the Holy Grail in assessment , 5. PartIn this issue of Perspectives on Medical Education, the paper by Holzhausen, Maaz, Cianciolo, Ten Cate and Peters presents a conceptual framework of entrustment decisions, drawing from work in domains of organizational psychology and military psychology . It aimsIn line with findings from research on performance assessments in medicine as well as other domains such as organizational psychology, the conceptual model furthermore implies that entrustment decisions are influenced by political, financial and cultural  factors in the organizational/educational context. This implies that we have to look beyond entrustment in the dyadic trainee-supervisor relationship. There is a wealth of research findings showing that exactly the culture (i. e. ‘the way we do things around here’) and contextual factors as described above may interfere with assessment quality. In medicine, for example, research findings clearly show that cultural values of autonomy in learning and practice, as well as aims to maximize efficiency in delivery of health care services, conflict with a culture that values direct observation or documentation of meaningful performance data , 12, 13.learning [others, psychological safety is about acknowledging that it takes time to learn, about seeing tasks as opportunities for learning, as well as about willingness to take the risk of speaking up and raising questions and concerns. Psychological safety implies a culture that values deliberation and collaboration – rather than decisiveness and efficiency [Actually, trust research in organizational psychology typically envisions trust as a substitute for control, reducing the need to monitor behaviours and emphasizing efficiency in organizational performance. From this perspective, our focus on trust and entrustment decisions seems to meet with current demands in health care to increase efficiency in attempts to improve quality and safety while reducing cost. Trust, in other words, fits approaches to health care delivery that focus on ‘execution-as-efficiency’ . The esslearning . Transfolearning . This imficiency . Researcficiency . PsycholTransforming our assessment systems to foster excellence in patient care thus requires efforts that should not be underestimated, even – or maybe exactly – when building our assessments on seemingly intuitive concepts such as trust.


Ranking enables coaches, sporting authorities, and pundits to determine the relative performance of individual athletes and teams in comparison to their peers. While ranking is relatively straightforward in sports that employ traditional leagues, it is more difficult in sports where competition is fragmented , with not all competitors competing against each other. In such situations, complex points systems are often employed to rank athletes. However, these systems have the inherent weakness that they frequently rely on subjective assessments in order to gauge the calibre of the competitors involved. Here we show how two Internet derived algorithms, the PageRank (PR) and user preference (UP) algorithms, when utilised with a simple ‘who beat who’ matrix, can be used to accurately rank track athletes, avoiding the need for subjective assessment. We applied the PR and UP algorithms to the 2015 IAAF Diamond League men’s 100m competition and compared their performance with the Keener, Colley and Massey ranking algorithms. The top five places computed by the PR and UP algorithms, and the Diamond League ‘2016’ points system were all identical, with the Kendall’s tau distance between the PR standings and ‘2016’ points system standings being just 15, indicating that only 5.9% of pairs differed in their order between these two lists. By comparison, the UP and ‘2016’ standings displayed a less strong relationship, with a tau distance of 95, indicating that 37.6% of the pairs differed in their order. When compared with the standings produced using the Keener, Colley and Massey algorithms, the PR standings appeared to be closest to the Keener standings , whereas the UP standings were more similar to the Colley and Massey standings, with the tau distances between these ranking lists being only 48 (19.0% pair order disagreement) and 59 (23.3% pair order disagreement) respectively. In particular, the UP algorithm ranked ‘one-off’ victors more highly than the PR algorithm, suggesting that the UP algorithm captures alternative characteristics to the PR algorithm, which may more suitable for predicting future performance in say knockout tournaments, rather than for use in competitions such as the Diamond League. As such, these Internet derived algorithms appear to have considerable potential for objectively assessing the relative performance of track athletes, without the need for complicated points equivalence tables. Importantly, because both algorithms utilise a ‘who beat who’ model, they automatically adjust for the strength of the competition, thus avoiding the need for subjective decision making. Ranking is an important task that enables coaches, applied scientists, sporting authorities, and pundits to determine the relative performance of individual athletes and teams in comparison to their peers or competitors. Ranking within talent identification, can also provide an objective assessment of the performance of young athletes relative to their peers, something that can be helpful when making important decisions about career progression , 2. WhilAccurate ranking of teams and athletes is something that poses a considerable challenge for many sporting authorities, and there is no clear consensus regarding the best approach that should be taken. In most sports, ranking is based on the accumulation of points awarded for performance during matches or tournaments. Leagues, such as those found in soccer and rugby, represent a classic example of this, with all the teams playing each other over the course of a season and the number of points accumulated indicating the respective standings. However, even within a league system such as this, the points system used can still vary between sports. For example: rugby league award two points for a win, one point for a draw and zero points for a loss ; soccer In recent years graph theory has yielded a number of algorithms that have proved remarkably successful in computer science. Perhaps the most pre-eminent of which is the PR algorithm used to power the Google search engine. This algorithm, first developed at Stanford University by Larry Page and Sergey Brin in 1996 , enablesIn order to assess the performance of the Internet derived algorithms, we also used three well-known sports ranking systems, the Colley , Massey The paper reports on a project that involved analysis of publicly available secondary data. Ethical approval for the project was granted by the Research Ethics Board of Leeds Beckett University.Public domain data from IAAF Diamond League website  were colA, which describes the relationships between web pages. In the graph described by the adjacency matrix, the web pages are nodes and the links between the web pages are the directed edges. The number of links leaving from any given node is called the ‘out-degree’ of that node  matrix populated entirely with the value 1/n.Finally, in order to ensure that the graph is strongly inter-connected and irreducible, the stochastic matrix, q, is then computed using the power method shown in q is a [1×n] vector containing the PR scores; z0 is a [1×n] vector containing the initial estimated PR scores, generally populated entirely with the value 1/n; and k is the number of iterations necessary to reach convergence.The vector containing the final PR scores, For the small web in From q it can be seen that node 3 has the highest PR, because it had no out-degrees, whereas node 1 was ranked lowest, reflecting the fact that it has 50% more links leaving the node than entering it.In order to apply the PR algorithm to the Diamond League event, we constructed a [33×33] adjacency matrix for all the competing athletes, which we updated after every race. For each race, any athlete who beat another received a ‘vote’ of 1 from the beaten athlete. So in a race comprising eight athletes, the winner would receive seven ‘votes’ from the other athletes, while the athletes who came second and third would receive six and five ‘votes’ respectively. This pattern would continue to the second to last athlete, who would receive one ‘vote’ from the last athlete, who would of course receive no ‘votes’. Where two athletes tied for a position, they were each considered to have voted for each other. After every race, the adjacency matrix was updated with the new ‘votes’ added to the existing ‘votes’ from the previous races. As such, the adjacency matrix maintained a precise updated summary of ‘who beat who’.The updated adjacency matrices were analysed using an ‘in-house’ PR algorithm, which was used to generate vectors containing the PR scores, together with network graphs showing the connectivity between the athletes. In keeping with previous work , when con is the number of products being assessed; b is a [n×1] vector containing the UP ranks for the various products; K is a [n×n] skew-symmetric adjacency matrix; and e is a [n×1] vector populated entirely with ones.Internet based retailers frequently rely on a ‘five star’ rating system to assess user preferences. This performs two functions; firstly it enables users to rate particular products; and secondly it allows similar products to be ranked so that retailers can compare their ‘performance’. This can be done by compiling a skew-symmetric weighted adjacency matrix from UP data, as described by Langville and Meyer . Once thu1… u6) rate four films (f1… f4) to produce a UP matrix, U, in which the rows denote the users and the columns denote the films. From this we can see that user U5, for example, has given film f1 a rating of five stars (the highest rating score) and a rating of three stars to film f4.In order to explain the methodology associated with a typical user preference rating system, we consider the example below, in which six users , we decided to use a reverse scoring system, in which the athletes who came first, second and third received one, two and three ‘stars’ respectively, with the number of ‘stars’ incrementally increasing for the lower finishing places. In this way, the number of athletes competing in any given race had minimal impact on the overall rankings, because the winner would always received one ‘star’, with the second athlete always receiving two ‘stars’, and so on. The rankings were derived for the individual athletes using the methodology described above. Because we used a reverse scoring system, the final ranking vector, b, was multiplied by –1 in order to make the ranking scores positive for the leading athletes.X, it is generally more common to use the number of points or goals that team i scored against team j  adjacency matrix for all the competing athletes, which we populated with data from all ten races. In order to ensure consistency with the other ranking techniques used, we adopted a ‘who beat who’ strategy, in which each athlete who beat another athlete receiving a ‘vote’ of 1 from the defeated athlete, in the similar manner to the PR algorithm. In the event of a tie between two athletes, a ‘vote’ of 0.5 was awarded to each athlete . Eq (13)v,  using vi is the combined ‘score’ of the ith team; wi is the number of wins of the ith team; and li is the number of losses of the ith team.Unlike the Keener method, which takes into account the outcome of individual matches between teams, the Colley algorithm utilises only the total number of wins, losses and games played to rank competing teams. It was developed by Wesley Colley in 2002 to rate teams in match-orientated sports  and utilrc is the Colley rating vector, which defines the ranking of the teams; and C is the Colley coefficient matrix defined as  adjacency matrix in the same manner as used with Keener algorithm. We used this to calculate for each athlete, the total number of contests won and lost against the other athletes, which we then used to compute the vector, v, using W, recording the outcomes of m matches between n teams. Matrix, W, is populated according to the following rules  adjacency matrix for all the competing athletes, which we populated with data from all ten races. Since the Massey method was developed for competitions in which teams play paired matches, we adopted a strategy that mimicked the scoring in a soccer match. So in a race comprising eight athletes, the winner was deemed to have scored seven ‘goals’ more than the last athlete, who was deemed to have scored no ‘goals’. Likewise, second and third athletes in the race were deemed to have scored six and five ‘goals’ respectively. This pattern continued until the second to last athlete, who scored only one ‘goal’ more than the last athlete. We used this matrix to calculate the cumulative points differential score for each athlete, which we compiled into vector, The final rankings produced by the various algorithms were compared with each other and also with the standings computed using the official IAAF Diamond League points system. In the 2015 season, for all the races, except the final meeting in Bruxelles, four points were awarded for first place, two points for second place, and one for third place . In the τdist is the normalized Kendall’s tau distance; N is the number of items in each ranking list; and Nd is the number of discordant pairs.In order to compare the standings produced by the various ranking systems, we calculated the Kendall’s tau rank distances between the respective standings for the top 23 athletes (i.e. the number of athletes ranked by the Diamond League ‘2016’ points system), which we then normalized  to compuIn addition, Pearson correlation analysis was performed using the paired ranking scores computed by the various systems for the respective athletes. Statistical analysis of the data was performed using ‘in-house’ algorithms written in ‘R’ and Matlab. For all tests, p values <0.05 were deemed to be significant.The standings computed by the PR algorithm for each competing athlete after every race are presented in The results in While the Colley and Massey algorithms yielded standings that were very similar to each other , the standings produced by both these methods were markedly different from those produce by either the PR and Keener algorithms, or indeed the Diamond League points systems. For example, the Colley and Massey algorithms ranked Usain Bolt and Marvin Bracy much higher, and Mike Rogers much lower, than any of the other methods. Notwithstanding this, some similarities were observed between the UP standings and the Colley and Massey standings, with the tau distances between these ranking lists being only 48 (19.0% pair order disagreement) and 59 (23.3% pair order disagreement) respectively, much smaller than the equivalent distances between the UP standings and the PR and Keener algorithms.The results of our study are promising and suggest that graph based algorithms have considerable potential as tools for ranking the performance of track athletes, without the need for complex tables. Currently, the ‘All-athletics’ World Rankings , 28 relyIn the present study we used the 2015 Diamond League 100m races because collectively they represented an asymmetric system of manageable size, which could easily be assessed. The Diamond League also had the added bonus of a points system, which we could use for comparison purposes. While the Diamond League points system reflects the idiosyncrasies of the competition, and therefore should not be considered definitive, it nonetheless proved a useful tool with which to assess the performance of the ranking algorithms. From In our PR model an athlete who beats another athlete can be considered as receiving a ‘vote’ from the beaten athlete. Consequently, the winner of a race involving eight athletes will receive seven votes. However, in the PR model these votes are not all equal, because beaten athletes with a higher PR score will make a greater contribution to the PR score of the race winner, than those from beaten athletes exhibiting a low PR score. As such, the PR algorithm tends to favour individuals who race more often and perform reasonably well , over outstanding athletes, such as Usain Bolt, who participate sparingly. However, the same would generally be true for a points based system. As such, both approaches tend to favour athletes who perform consistently well, over those who put in outstanding ‘one-off’ performances. So although the PR algorithm and the points system utilise very different methodologies, in the context of the Diamond League, they appear to achieve very similar results.When compared with the other ranking systems, the PR algorithm produced results that were most similar to those of the Keener algorithm, with a 26.5% pair order disagreement between the two ranking lists. This suggests that the Keener algorithm, as executed here, produces standings that capture some of the attributes displayed in the PR standings, and indicates that it may also have potential as a tool for assessing track athletes. Having said this, it is noticeable that the Keener algorithm ranked Marvin Bracy relatively lowly, despite this athlete winning the race in which he competed. This appears to be due to the fact that only seven athletes competed in Bracy’s race, whereas the Keener algorithm ranked Usain Bolt six places above Bracy, primarily because he won a race in which nine athletes competed. As such this represents a serious limitation of the Keener method, which may impede its application to track athletics.th and Kim Collins 16th, suggesting that the two algorithms detected different nuances. So while the UP, PR and 2016 points systems all agreed about the first five standings, below this the results for the UP algorithm diverged from those produced by the other two approaches. The primary reason for this is that the UP algorithm tends to average the scores achieved so that ‘one-off’ victors will tend to be ranked higher than more mediocre athletes who have competed many times. As such, the UP algorithm appears to share some of the characteristics of the Colley and Massey algorithms, which both ranked ‘one-off’ victors highly. Indeed, it is noticeable  than Usain Bolt (multiple Olympic champion) who finished first in the only race in which he ran. Although the PR algorithm also placed Kim Collins above Usain Bolt, the UP algorithm did not, placing Usain Bolt 6ticeable  that theLinear algebra based sports ranking models such as the Coley matrix method , 19 and The purpose of the study presented here was not to develop the perfect ranking algorithm, but rather to explore the potential for applying Internet related algorithms in a sporting context were competition is fragmented. With respect to this both the PR and UP algorithms appear to have potential. Because they are both essentially ‘who beat who’ models that automatically rank the contestants, they minimise any subjectivity that would otherwise be involved. Consequently, they have the potential to objectively rank individuals and teams in sports where competition between competitors can be sparse, such as in boxing, tennis and athletics, or in international soccer and rugby. In these sports, lower ranked competitors frequently compete at a more regional level, making comparisons between individuals and teams difficult. In athletics, the ability to assign a ‘fine tuned’ score to lesser ranked athletes based solely on who beat who, rather than an arbitrary points system, may be something of particular interest to coaches seeking to assess the true performance of developing athletes, and also sporting authorities seeking to prioritise funds. Such athletes often fail to reach the finals of competitions and therefore, under the IAAF system, are not awarded a placing score, making it difficult for the coaches to assess their true performance.While in the present study we used race position to construct the respective adjacency and UP matrices, we are aware that the difference in race time between athletes was also an option. However, in this study we decided against this because of potential differences between race tracks and variations in weather conditions, which might have compromised our results. Consequently, both the PR and UP models are essentially ‘who beat who’ methods that take no account of race times. While this approach appears well suited to the ethos of the Diamond League, we are conscious that our models could be improved by incorporating race times and plan to investigate this in the future. We are also aware that we have ignored other ranking systems that might prove useful with regard to track athletes, the foremost of which is perhaps Elo’s system which has been used for many years to rate chess players , and hasIn conclusion, we have shown that the PR and UP algorithms, when utilised with a simple ‘who beat who’ matrix, can be used to accurately rank track athletes. With specific reference to the IAAF Diamond League men’s 100m events, the PR model produces very similar results to those achieved using the Diamond League ‘2016’ points scoring system, but with more definition between the athletes, particularly in the lower ranks. By comparison, the UF algorithm captures other characteristics and may be more suitable for predicting future performance, say in knockout tournaments. As such, the algorithms appear to have considerable potential for objectively assessing the relative performance of track athletes, without the need for complicated points equivalence tables. Importantly, because the algorithms utilise a ‘who beat who’ model, they automatically adjust for the strength of the competition, thus avoiding the need for subjective decision making.


Addiction is a mental illness in which psychiatric conditions imply a prominent burden. Psychopathological symptoms in substance use disorder (SUD) patients are usually viewed as being assignable to the sphere of a personality trait or of comorbidity, leaving doubts about the presence of a specific psychopathology that could only be related to the toxicomanic process. Our research group at the University of Pisa has shed light on the possible definition of a specific psychopathological dimension in SUDs. In heroin use disorder patients, performing an exploratory principal component factor analysis (PCA) on all the 90 items included in the SCL-90 questionnaire led to a five-factor solution. The first factor accounted for a depressive “worthlessness and being trapped” dimension; the second factor picked out a “somatic symptoms” dimension; the third identified a “sensitivity–psychoticism” dimension; the fourth a “panic–anxiety” dimension; and the fifth a “violence–suicide” dimension. These same results were replicated by applying the PCA to another Italian sample of 1,195 heroin addicts entering a Therapeutic Community Treatment. Further analyses confirmed the clusters of symptoms, independently of demographic and clinical characteristics, active heroin use, lifetime psychiatric problems, kind of treatment received, and, especially, other substances used by the patient such as alcohol or cocaine. Moreover, these clusters were able to discriminate patients affected by addiction from those affected by psychiatric diseases such as major depressive disorder. Our studies seem to suggest the trait-dependent, rather than the state-dependent, nature of the introduced psychopathology dimensions of SUDs. Substance use disorder (SUD) individuals show an incredibly high comorbidity concomitance with mental illness, especially with anxiety, impulse control, and mood-related disorders , 2. Moreper se (The linkage between substance use (abuse or dependence) and mental illness is tricky. From a theoretical point of view, four possible explanations can be put forward: the first is that the manifestation of addiction may be facilitated by the presence of a mental disorder; the second is that SUDs elicit the onset of other mental disorders; the third is that the underlying causes of substance use and other psychiatric disorders may be the same; and the fourth is that factors linked to sampling, selection of instruments for diagnosis, investigation, and analysis could have led to an incorrect estimation of comorbidity. Even if the existing literature has explored the correlations between substance use and different areas of psychopathology, and put forward hypotheses about the mechanisms that trigger substance use and/or psychopathology, there is a broad gray, much less studied area dedicated to inquiring whether the symptoms often reported by SUD patients  have to be considered as merely a comorbidity, or whether they belong directly and intrinsically to addiction per se . This isActually, some criticism became public about the classical model of psychiatric comorbidity in the field of SUDs that leads to a high frequency of association between the two disorders. This close association raises doubts about whether the two conditions are actually independent, especially when taking into consideration the overlap between biological substrates and the neurophysiology of the psychiatric symptoms and addictive processes that are related to addiction , 12.per se was the only disease to have no specific psychopathology, and that all the symptoms and psychiatric clusters shown in SUD individuals had to be considered as merely manifesting “comorbidity.” The view we put forward is supported by analyses on diverse samples of SUD individuals, considering potential confounding factors that could be misleading in finding the right route for moving forward to the moment of identification of a specific psychopathology of addiction.Our V.P. Dole Dual Diagnosis research unit at the University of Pisa, Italy, has worked hard on this specific issue in recent years. It was difficult for us to believe that addiction Taking into account the ineliminable factor of uncertainty in the correct classification of symptomatology—as being intrinsic to the addictive disorder or as due to comorbidity—it seems best to try to approach the psychopathology of addicts by starting from a low inference level—rooted in the symptoms expressed by patients—rather than starting from a pre-established syndromic level such as that of DSM nosography. In this foundation, it was a priority to identify, in SUD subjects, psychological/psychiatric dimensions drawn from the spontaneous association between various symptoms. We started by subtyping patients, using a sample of heroin-dependent patients, and working with their responses to the Self-Report Symptom Inventory (SCL-90) survey. The choice of using heroin addicts was in line with our conviction that opiate addiction is a paradigm for the study of SUD . We consz-scores obtained for each of the five SCL-90 factors (dominant SCL-90 factor), subjects were allocated to one of the five mutually exclusive groups. The group whose dominant was “worthlessness and being trapped” comprised 150 subjects (14.2%), the group with “somatization” as its dominant gathered 257 subjects (24.4%), the group showing “sensitivity–psychoticism” as its dominant included 205 subjects (19.4%), the group identified by “panic–anxiety” as its dominant numbered 235 subjects (22.3%), and the group whose dominant was “violence–suicide” group profiled a cluster of 208 subjects (19.7%). These five groups were sufficiently distinct and failed to reveal any significant overlap. All these patients showed positive scores in their dominant factors only, alongside negative scores in all the others, the only exception being a small number of patients whose dominant was “worthlessness and being trapped,” who showed a positive score for the “sensitivity–psychoticism” factor. A discriminant analysis confirmed these results, indicating a percentage of correctly classified “grouped” cases as high as 95.26%.Using an exploratory principal component factor analysis (PCA) of the SCL-90 questionnaire, a five-factor solution was found. Seventy-seven items with a >0.40 loading were retained. The items that had shown the greatest loading supplied the names of the single factors. The first factor corresponded to a depressive “worthlessness and being trapped” domain that accounted for 29.9% of the variance. The second factor identified a “somatization” dimension that comprised 4.2% of the variance. The third factor marked out a “sensitivity–psychoticism” dimension that included 3.0% of the variance. Panic symptoms led to the fourth factor, named “panic–anxiety,” accounting for 2.15% of the variance. Finally, the fifth factor reflected aspects of “violence–suicide,” which accounted for 2.0% of the total variance. Taken together, the five factors accounted for 37.8% of the variance shown by the items. Considering the highest The “worthlessness, feeling trapped” dimension was the leading factor bringing together depressive, obsessive–compulsive, and psychotic symptoms. These feelings are frequently reported by SUD subjects at treatment entry, who talk of a feeling of being trapped in a corner, abandoned; they worry too much about difficulties, they feel guilty and report no sexual drive. Obsessive–compulsive symptoms focus mainly on patients’ doubts about their capabilities, the decisions they have to make, and their acts. Memory impairment and compulsivity are not present in any domain. Thought disorders consist of feeling alone even at moments spent together with other individuals. These subjects describe a feeling of inferiority, show interpersonal sensitivity (they are easily hurt), report phobic anxiety , and “often feel nervous and upset.” This factor is basically made up of obsessive, depressive, and psychotic features and is dominated by feelings of being trapped in a corner and uselessness. This dimension can be considered on the basis of the close linkage between SUD and mental disorders, in terms of the epidemiology of the two conditions, their psychological and neurobiological background and the shared psychopathological risk factors –22.The second domain (somatization) is distinguished by a number of anxious and somatic elements, which could be typical of opiate withdrawal feature. These patients complain of back pain, muscle aches, weakness and tiredness, heavy legs and arms, paresthesia, and loss of sensitivity somewhere in the body. Cold shivers and hot flushes are possible too, even stomach ache and nausea. Getting to sleep is difficult and, as a rule, when sleep comes, it is disrupted. The second dimension, resembling an opioid withdrawal condition, may be related to a request for treatment.The third factor (sensitivity–psychoticism) features psychoticism and sensitivity. Subjects think that people are looking at them and are talking about them, maybe organizing something against them. They think they are not respected because of their personal perspective. They believe that others do not sympathize with them or actually disapprove of their conduct. They feel uneasy or uncomfortable when they find they are being looked at by others, have to be in crowded places, or have to do things with others . These behaviors can be considered as psychotic when patients feel sure that others influence, control, or read their thoughts. This dimension can be considered in the light of the self-medication hypothesis, due to the antipsychotic action of opioids –30 or isThe fourth factor (panic–anxiety) can be summarized as a fear of going around alone, traveling by train, bus, or subway (agoraphobia), fear of feeling sick or sensations of dizziness, and episodes of critical anxiety. Generalized fear is a feature, with the need to avoid activities or places in order to prevent acute anxiety. This dimension too may be involved in the overlap between anxiety and withdrawal symptomatology, as the two conditions share physiopathological and neurobiological features –42.The fifth factor (violence–suicide) includes aggressiveness against others as well as self-direct aggressiveness. Rage, anger, and smashing things up are the key components of this domain. These individuals have a habit of arguing with others and showing high energy levels, together with returning to ideas about death. There is an extreme impulsiveness, which marks out the behaviors of SUD individuals, and should be assessed in light of the shared neurobiological background  and risk factors  –51.Therapeutic community sample (TC cohort) Major depression sample (MD cohort) .The main issue related to the identification of a specific psychopathology of HUD was the need to determine whether this five-factor (compound) solution obtained from a sample of HUD individuals entering agonist opioid treatment was the direct outcome of the specific condition of these patients , or whether it subsisted independently of the request for treatment. To better understand if we were facing a trait rather than a state nature for the proposed five factorial dimensions, we looked at confounding variables such as treatment choice, active use of substance, lifetime psychiatric problems, substance chosen, and major psychiatric conditions. To do this, we used two different cohorts of patients:To verify whether the five psychopathological dimensions identified in AOT cohort patients were in any case observable, independently of the treatment chosen, we compared the AOT cohort with heroin-dependent patients belonging to the TC cohort. Our expectation was that that these dimensions observed in a previous heroin opioid use disorder sample would be validated again in other samples of heroin addicts and that the severity of a subject’s psychopathology would be correlated with the specific treatment choice . The facWe verified whether any differences emerged between the five SCL-90 dimensions previously identified through the application of PCA in comparing heroin-addicted patients who had already been detoxified (DTX) with those who were not yet detoxified (NDTX) from heroin at the time of entering a Therapeutic Community Treatment. Detoxified patients were defined as those who reported having already been detoxified and not requiring agonist opioid treatment during the first month of TC treatment. According to our results , it is sTo explore the possible impact of comorbid psychiatric conditions on the five psychopathological dimensions set out above, we verified whether heroin-addicted individuals with (PC-HA) or those without (NPC-HA) known lifetime psychiatric problems showed any differences in these five domains. We considered PC-HA patients on the basis of the previous presence of a psychiatric diagnosis, suicide attempts, psychiatric hospitalization, and psychiatric welfare benefits at treatment entry or psychiatric treatment prescription while in a therapeutic community. Considering the TC cohort, NPC-HA and PC-HA patients failed to show any differences in most of the demographic characteristics. Conversely, older age, longer history of heroin dependence, being female, and general pattern of discriminated social status were associated with a higher proportion of heroin addicts marked out by their more severe psychopathology (PC-HA).The higher scores shown by PC-HA in the five psychopathological dimensions are in line with the predictably greater severity of psychological/psychiatric status in individuals with heroin dependence and psychiatric comorbidity. Anyhow, our studies show that even if the presence of lifetime psychiatric problems appears to be correlated with the severity of psychopathology (as documented by the SCL-90 scores), it does not seem to be related to its quality: actually, the “panic–anxiety” and “somatic” dimensions are the only factors that discriminated patients belonging to the PC-HA from the NPC-HA group. According to multivariate analysis, none of the other three domains were able to predict the allocation of subjects to the NPC-HA or PC-HA group, so their persistence as components of the SCL-90-defined structure of opioid use disorder may be considered independent of the presence of lifetime psychiatric problems .We decided to explore the specific burden arising from the substance of abuse in identifying the psychopathological structure. We considered subjects affected by cocaine, alcohol, and heroin dependence according to a diagnosis based on clinical judgment, availability of the SCL-90 questionnaire, and an age of 18 years old or more, leading to the selection of a sample of 2,314 individuals . Patient“Panic–anxiety” was the prominent psychopathological dimension of SUD individuals using heroin, cocaine, or alcohol as primary substance. By contrast, “violence–suicide” for the group of alcohol dependence subjects (11.4%) and “worthlessness-being trapped” for subjects with cocaine or heroin dependence  turned out to be the least frequent dimensions. “Somatic symptoms” dimension was the only one showing statistically significant differences between groups—in particular, highlighting a stronger representation of heroin-dependent subjects than of cocaine-dependent ones; the “sensitivity–psychoticism” dimension was more strongly represented in alcohol-dependent subjects than in heroin-dependent ones; “violence–suicide” was more frequent in heroin-dependent than in cocaine-dependent or in alcohol-dependent subjects.A positive association was confirmed using a multinomial logistic regression between both the “somatic symptoms” dimension and heroin dependence versus cocaine dependence and, once again, between both the “sensitivity–psychoticism” domain and alcohol dependence versus heroin dependence.The further logistic regression analyzing cocaine versus alcohol as primary substance of abuse did not detect any significant association between the five domains and the primary substance of abuse.“Panic–anxiety” was the most strongly represented psychopathological dimension for all of the three groups of patients. Group by group, the least frequent dimensions were “violence–suicide” and “sensitivity–psychoticism” for the group of patients with alcohol as secondary abused drug, “violence–suicide” for patients with no cocaine or with alcohol as secondary drug, and “worthlessness-being trapped” for patients with cocaine as secondary drug of abuse. No statistically significant differences were observed between the three groups in any of the five SCL-based psychopathological domains.Considering major psychiatric diagnosis, it is important to demonstrate that these five dimensions were able to differentiate SUD patients from other psychiatric patients.Thus, we compared HUD patients with MD patients on the basis of the five SCL-90 dimensions already identified in heroin SUD patients. If our five dimensions are directly correlated with heroin SUD, we would expect to find a higher prevalence of these dimensions in heroin-addicted SUD patients than in MD ones.The sample consisted of the sum of the AOT cohort and MD cohort, reaching a total of 1,476 patients fulfilling the DSM-IV, DSM-5 criteria for heroin dependence, heroin SUD, or, alternatively, MD . Heroin per se. These five-factor dimensions appear to be different from the dimensions that are related to mental illness patients and remain stable no matter which confounding factors are considered, among those that are most pertinent when we are dealing with addicted patients.The results of our studies open the way forward to the possible identification of a specific psychopathology of heroin addiction and addiction When the choice of treatment is considered, the model of SCL-90 used by us showed the same five-factor solution for both TC and AOT groups of individuals. Looking at the association between the five psychologically and/or psychiatrically dominant groups and their allocation to TC or AOT treatment, the “violence–suicide” and “somatic symptoms” dominant dimensions were correlated with AOT. This result should be interpreted after taking into consideration the fact that AOT patients are better equipped to handle the features of violence and suicide, as well as showing a positive effect on somatic dimensions that may be closely related to withdrawal symptoms . ConsideConsidering the active use of heroin, the “somatic dimension” is the only differentiating dimension between DTX and NDTX groups that may easily be explained on the basis of the features that this dimension comprises. The SCL-90 items included in this dimension correspond to a number of somatic complaints  , which aIndeed, although a lower severity of the SCL-90 scores of DTX patients was observed in all the psychopathological dimensions than in the scores recorded for the NDTX ones, its degree was greatest in the “somatic” dimension, followed by the “worthlessness-being trapped” and “violence–suicide” dimensions, and was lowest in the “panic–anxiety” and “sensitivity–psychoticism” ones. Actually, the magnitude of the reduction in the severity of symptoms distinguishing the first three dominant SCL-90 factors may have allowed some of the DTX patients to show their highest scores in the dimensions least affected by detoxification, such as the “panic–anxiety” and “sensitivity–psychoticism” dimensions. This explanation is consistent with our findings on the easier resolution of the physiological symptoms of withdrawal compared with the psychological ones. One particularly instructive example is anxiety, which, together with other affective components of the withdrawal condition—those related to the reduction of dopamine tone and to the activation of the stress system—tends to persist longer after the interruption of heroin use –70. In tWhen we considered the presence/absence of lifetime psychiatric problems, the differences that emerged were consistent with previous work in which the same topic was explored, but different investigative analyses were used  and theyper se, it was important to exclude another confounding factor—none other than the specific substance of abuse: heroin, cocaine, or alcohol, leading to the consideration that this structure is largely independent of the specific drug used. The differences that emerged were definitely those related to the specificity of action of the single substance abused: the “somatic symptoms” dimension, for instance, was better represented in heroin-dependent versus cocaine-dependent subjects, and the “sensitivity-psychotic” dimension showed a higher percentage in alcohol versus heroin groups. On the other hand, the greater association of alcohol-dependent subject with the “sensitivity-psychotic” dimension rather than the heroin-dependent group could be due to the presence of a pre-eminently psychotic aspect of alcohol withdrawal or to the progression of alcohol dependence per se . It is important to notice that each sample was collected from several different outpatient clinics or care units—a circumstance that led to some difficulties in obtaining an “objective” evaluation. In any case, having a self-driven questioner makes it possible to investigate symptoms from a dimensional perspective instead of using a group of several interviewers—a feature that inevitably leads lead to a non-uniform interviewer-related objective rating. It must, surely, be taken into account that some individuals may hide some symptoms, either voluntarily or involuntarily. In the end, due to the lack of any observer-related “objective” evaluation, caution is needed in interpreting these results.Using questionnaires to check the tendency of patients to lie is bound to function as a factor that helps to ensure the fairness of our data.The individuals involved in our study were without any formal psychiatric diagnosis. It is important to know that in Italy a diagnosis is formulated at a late stage of treatment, either in addiction facilities or local units. The impact of psychiatric problems cannot be discriminated by using the SCL-90 questionnaire, and, surely, we cannot say whether or how strongly the profiles identified may correlate with a specific diagnostic criterion. Of course, a formal and objective psychiatric diagnosis would have to distinguish between subjects who have and those who do not have a significant psychiatric condition.Another limitation in using the SCL-90 scale is that it was administered at treatment entry only; the selection of one single time means highlighting only that specific moment in the life of a heroin addict; we certainly know that some symptoms may vary in accordance with the different stages of the disease, whereas some may improve or at least be reduced in their intensity due to a specific kind of treatment leading to a sort of underweighting or overweighting within our sample.Moreover, the TC cohort and the OAT sample show differences in several factors . First, diagnosis in the two samples was inevitably differentiated; considering the DSM-based criteria applied in the OAT sample and the clinically based criteria used in the TC sample, bias should be allowed for. In this light, it is important to consider that clinicians have to use a careful approach to dependence diagnosis when they choose a TC program for their patients (considering the limitations on patients’ freedom in TC that lead to a high level of dropouts), which may entail the selection of patients who have a severe condition. On the other hand, one cannot exclude either the opposite situation in which individuals in the TC sample did not fully reflect the DSM diagnostic criteria. One consequence is that the magnitude of the measures of association used in our study could be underestimated or overestimated.Our studies shed light on a specific aggregation of psychopathological symptoms in cases of HUD—a fact that strengthens the feasibility of the five-factor solution. It is now possible to say that these aggregations of symptoms are stable regardless of demographic and clinical characteristics, kind of treatment chosen, active involvement in substance use, lifetime psychiatric problems, and the substance chosen. These results pave the way to the delineation of a trait nature in place of a state nature in the perception of the structure of these five-factor psychopathological dimensions of heroin addicts. Moreover, the results shown by implementing a rigorous comparison of different substances of abuse allow us to define addiction as a unitary condition.AM and IM drafted the strategy of the review and the present manuscript. PP, SB, and AM reviewed the literature. SB and LR critically revised the article. All the authors read and approved the final manuscript.IM served as Board Member for Mundipharma, D&A Pharma, Reckitt Benckiser Pharmaceuticals, and Lundbeck. The other authors declare no conflict of interest. The sponsors had no role in the study design, in the collection, analysis or interpretation of data, in writing the manuscript, or in the decision to submit the manuscript for publication.


A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants’ personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient. From the early 1960s–1970s, psychedelic drug-assisted psychotherapy was researched in the United States as a treatment for cancer-related psychological and existential distress. These trials included several hundred participants and showed improvements in depression, anxiety, fear of dying, quality of life, and pain . BuildinTo better understand participant experiences, in-depth interviews were conducted with 13 participants treated in the Supplementary Figure S1 for an overview of study design) and two studies utilizing qualitative analysis of interviews from a subset of participants in the main trial  at enrollment. She was a full-time working professional and identified as an atheist at the time of her enrollment. Brenda was divorced and had two adult children. Upon screening, she identified as hallucinogen-naïve and met criteria for Adjustment Disorder with Anxiety, Chronic.Brenda’s psilocybin experience was a “roller-coaster kind” of train ride. She described the music as being an important catalyst throughout her journey. She discussed a comforting “whirring” sound throughout the beginning of her experience that she felt was “taking her in.” At one point, Brenda felt she was contently lying on a damp cloud and thought to herself, “If this is the way it’s going to be, it’s going to be really interesting. This is going to be really amazing. And I’m ready to go.” From there, she described feeling outside of time and space, “I felt out of space and time in a way that was really, really, really comforting and beautiful.” Brenda described an experience of interconnectedness and unity, “I was the cloud, I was everything, and that was the theme throughout the whole [experience], that I was all this –this was me. And it was so wonderful… to believe that. And I still do- that is me.”Brenda also felt as if she experienced her own death on two separate occasions during the experience and emerged both unafraid of death and viewing it as a beautiful component of existence. On the first occasion, she said, “I went into this black area and it was just wonderful... I just thought to myself... I think this might be what people experience when they die.” Her second encounter with death included seeing, “This brick thing that was a lot of bricks, and I realized this was a kind of crematorium... I was just part of this big beautiful world... and that’s what’s going to happen when I die... maybe death is a beautiful thing.”Her experience also unearthed childhood memories of sexual assault that she realized remained unhealed. Brenda acknowledged the study as a catalyst to begin healing from this trauma. Her data depicted decreased anxiety and death anxiety. When questioned on how the session altered her life, she responded, “What’s so funny is that nobody can really see it, but yet, for me, everything has changed…I feel more contented and happy about my place in the world in all the things I’m doing.” Her data also showed an increase in spirituality, as illustrated in her follow-up interview; “So I think that’s also opened up to me tremendously – a spiritual piece. And I’ve never been religious; I’m not religious particularly at all. And I feel like I’ve really connected with a spiritual side in myself as well.” After the trial, Brenda became interested in pursuing her relationship with this new aspect of herself, and began seeking out opportunities to recollect and re-experience elements of the experience through meditation. She said:I’ve been exploring whether I can bring back other sensations from it…I have been able to, and I’ve been doing a lot of meditating. I got into meditating afterward because it was like, ‘I just don’t want to lose this,’…I have a house up by a mountain monastery and I went up there, and that was very comforting to connect that way… I really felt like there was a real connection with Buddhism and meditation and the psilocybin experience for me. And I’ve been doing that everyday.Figure 1 and Supplementary Figure S2).The cases presented here were selected because their experiences were unique, but also represented several themes identified in published qualitative studies from this trial. These descriptions are not meant to be generalized. However, several broad conclusions can be drawn from these cases. Primarily, none of these participants had an experience dominated by any single theme. Rather, their experiences were rich in multiple thematic areas, while still retaining personal, meaningful, and tangible content. These four participants presented with varied psychological needs at enrollment, including symptoms of anxiety, depression, and other measures of existential distress. These distinct needs were met post-psilocybin treatment, and benefits were sustained throughout follow-up, regardless of the thematic content of their experience , with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the institutional review board of the NYUSoM.SR was the principal investigator of the parent trial that served as the platform for the data collection presented in this manuscript. JG, APB, and SR acted as study therapists for the parent trial that served as the platform for the data collection presented in this manuscript. TM, AB, and GA-L acted as study coordinators and/or performed data collection for the parent trial that served as the platform for the data collection presented in this manuscript. SM, TM, SP, and LO contributed to the drafting of this manuscript. All authors contributed to the conceptualization and writing and approved the final version of this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.