Drawing on surveys of religion and values in Great Britain, this paper suggests that Peter Berger’s paradigm of two pluralisms can be usefully supplemented by taking account of a third kind of intensified pluralism. This involves the breakdown of the boundaries between religions, and between the religious and the secular, and is therefore a pluralism of de-differentiation. It helps explain many features of contemporary religion and identity, including the rise of the “nones” and the increasing reluctance of each new generation to identify with religious (and secular) labels and packages. Peter Berger’s two pluralisms offer us a useful new paradigm for understanding religion in the modern world. First, there is religious pluralism; second, the pluralism of religious and secular coexistence. Because these two kinds of diversity now exist together in most societies, criss-crossing one another, they result in an overall intensification of pluralism, not least in the individual mind Berger .Here I want to suggest that this paradigm can be extended and made even more powerful by paying attention to a third kind of pluralism which has close connections with the first two, but goes beyond them. This is a pluralism of religious de-differentiation, closely tied up with a wider de-differentiation of previously more separate social domains, which many countries including Britain and the United States are experiencing today, and which in religious terms is signalized by the growing number of those reporting “no religion” – the so-called “nones”.I came to realise the value of such an extension of the Berger paradigm in trying to make sense of several extensive surveys of the values and beliefs of the British which I carried out with the survey company YouGov in 2013 and 2014,de jure. This is clear. But my surveys reveal an even deeper kind of pluralism, since a growing proportion of British people now refuse to categorise themselves as either religious or secular, and display notably variegated beliefs which are impossible to fit into neat religious or secular schemas. Combining this evidence with recent qualitiative studies makes it clear that the situation cannot wholly be accounted for by the fact that people are not neccesarily neatly religious in one compartment of social life  and secular in another . Nor do more than a tiny number identify with more than one religious tradition . They are plural in a different sense.Britain is, as Berger would predict, plural in cultural and religious terms – even more so than the USA – and it also has a pluralism of the religious and the secular, de facto if not least likely pluralists. Not only does their tradition offer clear, centralised moral and dogmatic instruction, but they are a religious minority in Britain, with a long history of sporadic persecution and disadvantage, especially relative to the majority church, the Church of England. As such, they can be expected to have a relatively strong and rather homogenous identity, built around what Steve Bruce calls “cultural defence”.Let me take Roman Catholics in Britain as an example, because they are in many ways the Self-identified Catholics today constitute about 10 % of the population of Great Britain.Nor do a majority of Catholics label themselves “religious.” Only a fifth describe themselves as such, a tenth as “spiritual,” and another fifth as “both.” The greatest proportion, one third, say “I would not describe myself, or my values and beliefs, as spiritual or religious.” Overall, a quarter of self-identified Catholics do not believe in God, and over half do not go to church. A majority do not identify as either “religious” or “spiritual”, when presented with a range of other options. A third say that they practice no spiritual activity in private. And, rather delightfully, one in five self-identified Catholics report that they are “not influenced by any religion at all”.The official Catholic Church would, and regularly does, say that this shows that Catholics need better instruction and discipline. Older paradigms in the study of religion say that they are gradually secularising. Both are asserting that Catholics have departed from the norm of what these authorities consider to be “real religion”, but my surveys show that neither offers an adequate explanation.For one thing, belief in God remains high amongst Catholics. Virtually all churchgoing Catholics believe in God, as do 70 % of self-identified Catholics taken as a whole.at all from their religious leaders, local or otherwise. They may respect or admire them, but they don’t do what they say. Similarly, the practice of churchgoing has fallen away amongst younger Catholics: 1 in 3 over-60s attend weekly, but only 1 in 8 of those under 60. And only 36 % of Catholics say that they view the Catholic Church as a positive force in society.4So most Catholics have not simply been secularising – abandoning faith in something “beyond”, to use Berger’s useful definition of religion – altogether. What they seem to have fallen out of love with is “religion” and their Church. As Clive Field  has arguIn other words, a growing proportion of Catholics, especially younger generations, retain the Catholic label and some elements of religiosity, but have distanced themselves from Catholicism as an authoritative “package”, and an off-the-shelf religious identity.Standing back to look at Britain as a whole, it is clear that what we find amongst Catholics is not atypical. Neither the categories of denominational and religious identification , nor those of religious or secular, signify in the way they once did. A greater pluralism seems to have overwhelmed them, and rendered them much less useful than they once were.The single most important, indeed epoch-making, fact about religion in Britain today is that the proportion of people identifying as having “no religion” is set to equal or overtake that of “Christians” within a few decades. Indeed, as Table 6However, a really crucial point is that “no-religion” does not simply equate to “secular” and “atheist”. Whilst only 16 % of nones believe in God, most are indifferent about the issue of God’s existence, rather than certain about “His” non-existence. Similarly, just 7 % of the population say they are influenced by humanism or secularism, and, as Table Only a small proportion of those who report having no religion are actively hostile to religion. I identified such “hostile nones” as those who say they have no religion, are atheist, and agree that both the Church of England and the Roman Catholic Church are each a negative force in society. They amount to just 13 % of nones, and 5 % of the population. These “secularists” are disproportionately male, and are just as likely to be found amongst older as younger generations. They do not appear to be growing anything like as fast as the unaffiliated “nones”, and there are no more of them in younger than older generations.Moroever, indifference to “religion” is not unique to “nones.” It is shared by a significant number of people who identify as Jewish, Christian, Buddhist etc. In total, only 47 % of those who report a religious affiliation describe themselves as religious and/or spiritual, and over a quarter say they are not influenced by religion. Equally, there are sizeable numbers of religiously-affiliated people who are atheists and agnostics – 63 % of those who identify as Buddhist, 42 % of those who state their religion as Jewish, 33 % of all Christians, 11 % of Muslims.7Clearly old categories for understanding pluralism don’t seem to be working very well. Most people can’t easily be categorized as Christian, Buddhist, Jewish or whatever. Even if they tick that box on a survey, they defy the norms of what Christians (or Catholics), Jews, or Buddhists are meant to be like. They may believe in God, but say they are not religious; they may say they are Catholic but not believe in God; they may say they are Jewish but not influenced by religion – and so on.Berger  has a goMy surveys point to the same blurring of boundaries. More and more British as well as US people are “non-religious”, but this does not mean they are secular. “Non-religion” is not really an identity category at all, it’s an artefact of pre-existing, modern survey categories – a pollster’s clumsy recognition that the standard categories of Christian, Muslim, Buddhist have ceased to be relevant to an increasing number of people. And even those who can still tick the old religious boxes don’t necessarily behave or believe in the way they are expected to. The categories of “nones” and “non-religion” are chiefly important as a sign that the old classifications are breaking down. My suggestion is that we are seeing the arrival of a third, intensified, kind of pluralism: a pluralism of religious de-differentiation and deregulation.This third kind of religious pluralism is evident at the level of individual lives, and has a social-structural correlate in the de-differentiation of functions and sectors of post-industrial societies. Functional differentiation is, of course, a particular historical episode, associated with industrial modernity and the modern secular state. It is under pressure from under various late modern pressures, including the realisation that the ‘wicked problems’ facing the world today – from climate change to obesity – cross many different social domains, and require connected responses. This situation has important implications for religious pluralism.Social differentiation did not just undermine religion, reducing its public sway, it also changed it. As Casanova  argued sBoth nationally and globally, this process tended to reify the existence and power of a small, authorised set of “world religions”, and denominations within them. They were characterised by some combination of a male leadership and clear teachings, practices and boundaries of orthodoxy or orthopraxy. State bureaucracy encouraged this process, which made classification, representation, enumeration, communication and control easier. There is a colonial and then a post-colonial phase to this process.Recent intensified globalisation both strengthens and weakens such religious reification. It strengthens because religions respond by strengthening internal transnational links, sharpening their global ‘brand’, consolidating themselves in relation to transnational political and other arrangements, and defining themselves in relation to one another Beyer . But theOne of the most important acids of the modern religious settlement is growing affluence worldwide, the creation of a global middle class, and expanding individual expectation of “voice and choice”. The latter, supported by both democracy and consumer capitalism, is starkest in relation to women’s often dramatically improved status and power, but evident more widely. At the same time, there is a massive expansion of education and a startling deregulation of information, both aided by the internet and the digital revolution. This undermines the virtual monopoly of religious knowledge and practice which religious professionals were able to consolidate in the modern era. Religious ideas and symbols float free on a scale never seen before, becoming available to any “seeker”, whilst social-networking media make it much easier to establish new religious networks and groupings whether real, virtual or both. These interlinked processes undermine the established entitlements of state-recognised religious leaders, and the bureaucratic and bounded forms of religious organisation on which their power rests become something of a liability as flexibility and meaningful lay participation become more essential to success.So on the one hand, “modern” religious authorities lose their ability to police their own boundaries and maintain control and purity, whilst on the other hand, ordinary people feel new entitlements in relation to religion, as in other areas of their lives, and wish to think and choose for themselves rather than merely obey and be dutiful. In Britain, for example, my surveys of views on a range of ethical issues reveal that the overwhelming majority of the population (over 90 %) are liberal in terms of their commitment to individual choice rather than some other authority, and that most say that they rely on their own judgement and conscience to make important decisions . Not surprisingly, many such liberals are critical of what they see as the authoritarianism of established forms of religion. Some abandon it altogether, a few become actively hostile, others actively seek, find and create spiritual alternatives. But most draw on select elements of religion which they still find meaningful , abandon other elements , and meld them all together with a wide range of other sources of significance.This is what I mean by the new, intensified form of de-differentiated religious pluralism. It accounts for the fact that such a large and growing number of people now think of themselves as having “no religion”, for by this they mean the “packaged”, “dogmatic” religions of modern societies. They are rejecting something very particular, not necessarily the much broader phenonomenon of religion, or all aspcts of it, or ways it may be recreated. They do not necessarily become atheists, or abandon the belief that there are things beyond this life which give it meaning. Most do not abandon all aspects of their inherited religions to become neatly and hygienically secular, and they are not usually neatly religious in some domains of their life and secular in others. Nor do they resort to some sort of untrammelled “pick and mix” approach to religion: they are limited in what they “pick” by the religions with which they have had contact, and by the normal constraints of ethnicity, class, education, and the knowledge and networks to which they give access.Importantly, people are decreasingly likely to think or act in terms of a neatly differentiated religious realm – such as that so well signified during the modern period by churchgoing on a Sunday morning. They are increasingly likely to engage with spiritual meaning across the various compartments of their life, and not merely in private. Consider, for example, how mindfulness meditation is now practised in healthcare settings, workplaces and so on, or in which spiritual and moral development is integral schooling in Britain.Far from being corrosive of religion per se, this de-differentiating and increasingly de-regulated situation provides enormous opportunities for the new – and old – religious providers and entrepreneurs who are able to take advantage of it. Bewildering numbers set up stall in the new religious market place, offering an enormous variety of “products” for various niches. Many still draw on the existing “world” religious traditions, indeed some claim to be their uniquely faithful representatives – religious fundamentalists being a good example. Others at the opposite end of the spectrum rework or self-consciously invent new religions for a post-modern clientele Cusack . The entIn this context, the old religions of modernity live on, desperately trying to shore up their defences and find new opportunities. Many try to sharpen their boundaries with clear statements of belief, strictness in moral teaching, and so on. Having a charismatic leader, like Pope Francis, may help, but will not guarantee obedience or faithful allegiance. Nevertheless, such religion continues to be supported by the fact that states, and international governing alliances, still recognise, register and otherwise legitimate these old forms of religion and their leaders . So at the macro-level in particular the differentiated, modern, religious order continues, even though at the meso- and micro-level it is increasingly hollowed-out and “polluted”.I believe that many late-modern societies, including Britain and the USA, are thus in a transitional phase at the moment, in which the differentiated modern mode of religion persists alongside new de-differentiated, proliferating alternatives. Because the former is much more threatened by the latter than vice versa, one of its main defensive strategies is to deny that new forms of religion count as religion at all. Some academics take the same approach. But those involved in the new forms of “religion” are generally untroubled by having the label denied them. The growing association of religion with violence, reinforced by Islamic terrorism, only strengthens their desire to distance themselves from the toxic brand which is religion. A few prefer the word “spirituality”, but a growing number simply identify as having “no religion”, without necessarily losing interest or involvement in many aspects of what religion can provide.The fact that we are in transition is revealed by the generational split in religious identification. The old categories of religious belonging remain relevant to those aged 60 and above (a majority of whom are Christian in Britain), but are increasingly less applicable to younger cohorts. Even those who still accept these labels, particularly in the middle age cohorts, fill them with a much more mixed content than religious and political leaders would like. Meanwhile, the old-style modern religions, most notably the churches, often become increasingly clerical and authoritarian. It is a mutually-reinforcing dynamic: the top-down tendency to purify fights against countervailing trends of de-differentiation and mixing from bottom-up.None of this is completely new. Historians have taught us that even in medieval Catholic Europe ordinary people might hold or develop idiosyncratic and far-from-orthodox versions of religion. Some religions, like Hinduism, were always more resistant to systematisation and rationalization. What late, globalized, modernity does is to make the process of democratized reinvention and plundering much easier and less costly by on the one hand unlocking religious resources, and on the other hand undermining the power of traditional religious authorities to control them. This greatly enhances the capacity of ordinary believers to “do religion” for themselves, and a culture which privileges individual voice and choice only makes this seem more desirable.Berger’s paradigm of twin pluralisms offers an extremely useful tool for making sense of religion in the modern world. The lens of religious pluralism helps us see how different religious traditions co-exist and relate within a given society, and what this means for their plausibility. It becomes more powerful when taken together with the lens of religious-secular pluralism. This not only helps us differentiate between various national state regimes in terms of their self-understandings, protocols, and modes of governance of religion, it also helps us look at different sectors of society – e.g., schools, hospitals – their self-representations, relations with religion, and so on. Both forms of pluralism are bound up with modern functionally differentiated societies, and with the modern nation states so central to them. They have been intensified by the flows of globalization, and its compression of space and time. Using both lenses, we understand much more about how individual lives are affected by pluralism.Increasingly, this twin pluralism is joined by a new form of pluralism characteristic of post-industrial, affluent, highly-educated, late modern societies. It is bound up not with differentiation but with de-differentiation, and is a pluralism which has to do not just with clearly demarcated social functions and domains and their religious or secular profiles, but the breakdown of clear boundaries between them. Religion has leaked into areas of life from which it was temporarily exiled by modern projects; the religious-secular distinction becomes blurred or meaningless; the category of religion becomes toxic; the reality of religion as a separate domain of socio-political life wanes; religious professionals lose status and authority; people become their own priest. Increasing numbers of us inhabit the complex intersections between these three kinds of pluralism, as the old religious order is overtaken by something new.


The current field of multiple sclerosis (MS) research is an active and highly interesting one: structural abnormalities such as inflammatory lesions and brain atrophy are studied with a wide array of advanced neuroimaging techniques . These tHistorically, most early imaging studies have used the paced auditory serial addition test (PASAT) to study cognition in MS, a task that measures information processing speed –10. ThesThe body of literature of that point in time led to our previous hypothesis of functional reorganization in MS . This hyHowever, the previous model was mostly based on task-based activation studies, while the connectivity field was still in its infancy. As the concept of functional reorganization was gaining support, the field was primed for finding cognitively relevant connectivity changes. Interestingly, recent studies have mostly related increased functional connectivity to cognitive dysfunction, raising doubts on the previous concept of functional reorganization in MS. In this paper, we will review this recent functional connectivity literature and reiterate the case around functional connectivity changes in MS and their potential effects on cognition. Which reported connectivity changes can be justifiably said to be “compensatory” or “beneficial”? Which are likely “maladaptive”? Can any such predicate be arrived at all, based on the neuroscientific studies available? Is it perhaps time to revise our previous model of functional reorganization?Resting state network changes have been observed in relapsing remitting MS (RRMS) patients, both within and between almost all resting state sub-networks . The DMNUnfortunately, results from seed-based analyses investigating other structures like the DLPFC have not been very consistent either. One such study  found a Studies looking at several other cognitively relevant structures such as the thalamus, hippocampus, and cerebellum have shown varying patterns of connectivity in MS as well. Thalamic atrophy has well-known and strong effects on cognition in MS , which apost hoc. This process actually seems quite complicated, however, as cross-sectional studies have related both connectivity increases and decreases to cognitive dysfunction in MS. Therefore, the studies that do claim that changes might be beneficial for cognitive performance in MS might not have enough evidence to do so. In truth, we are currently unable to disentangle “good” from “bad” and are strongly limited by the cross-sectional nature of almost all of these studies.As described above, the body of literature on cognitively relevant connectivity changes in MS is currently difficult to interpret. As it seems, our previous model for functional reorganization is incomplete and the term is currently used in a number of ways and lacks a clear definition. Additionally, these findings were studied across the spectrum of clinical and cognitive phenotypes in MS, with very different methodological and statistical approaches, leaving the data ambiguous in places. Some studies now refer to any connectivity change as functional reorganization, leaving it to the reader to disentangle “beneficial” or “maladaptive” functional reorganization For example, suppose that a functional connectivity increase is observed in cognitively preserved patients, and a decrease in a cognitively impaired patient group. Although many studies interpret such a finding as cognitively relevant, as described previously, such data could, in fact, be interpreted in several ways. First, the functional connectivity increase in cognitively preserved patients might reflect “beneficial” functional reorganization, delaying cognitive impairment. In impaired patients, this effect of functional reorganization is then lost. Second, the functional connectivity increase in cognitively preserved patients might be a “maladaptive” response, following, e.g., disinhibition, heralding an imminent network collapse, and further deterioration into cognitive impairment. Third, the functional connectivity increase in cognitively preserved patients could be an unrelated epiphenomenon. Or, that the connectivity increase is related to structural damage, but that it has no direct impact on cognition at all. And finally, given the fact that most studies are cross-sectional, it cannot be excluded that the frequently observed functional connectivity increases in patients with cognitive impairment are, in fact, “beneficial.” It is possible that such increases are, e.g., a bleed through of beneficial functional reorganization from the cognitively preserved stage. This could be due to a poor definition of cognitive impairment and/or plastic changes that persist throughout this stage of the disease. The only way we are going to understand the cognitive role of functional connectivity changes in MS will be to study them over time.Preliminary longitudinal studies linking connectivity changes to cognitive rehabilitation , 43, as combined set of functional changes in MS has become much more complex, leaving our previous model of functional reorganization in MS incomplete and too simplistic. After exploring abovementioned individual structures and sub-networks in MS has not made matters much clearer, it is now opportune to look at connectivity in another way. One option is to take functional connectivity values and convert them into a more holistic network model of the entire brain. This so-called graph analysis approach  imaging tools to monitor cognitive deficits can hopefully be taken.All authors contributed to the conception, drafting, revising, and finalizing of the manuscript and agree to be accountable for all aspects of the work.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.


Structured information within patient medical records represents a largely untapped treasure trove of research data. In the United States, privacy issues notwithstanding, this has recently become more accessible thanks to the increasing adoption of electronic health records (EHR) and health care data standards fueled by the Meaningful Use legislation. The other side of the coin is that it is now becoming increasingly more difficult to navigate the profusion of many disparate clinical terminology standards, which often span millions of concepts.The objective of our study was to develop a methodology for integrating large amounts of structured clinical information that is both terminology agnostic and able to capture heterogeneous clinical phenotypes including problems, procedures, medications, and clinical results . In this context, we define phenotyping as the extraction of all clinically relevant features contained in the EHR.The scope of the project was framed by the Common Meaningful Use (MU) Dataset terminology standards; the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), RxNorm, the Logical Observation Identifiers Names and Codes (LOINC), the Current Procedural Terminology (CPT), the Health care Common Procedure Coding System (HCPCS), the International Classification of Diseases Ninth Revision Clinical Modification (ICD-9-CM), and the International Classification of Diseases Tenth Revision Clinical Modification (ICD-10-CM). The Unified Medical Language System (UMLS) was used as a mapping layer among the MU ontologies. An extract, load, and transform approach separated original annotations in the EHR from the mapping process and allowed for continuous updates as the terminologies were updated. Additionally, we integrated all terminologies into a single UMLS derived ontology and further optimized it to make the relatively large concept graph manageable.The initial evaluation was performed with simulated data from the Clinical Avatars project using 100,000 virtual patients undergoing a 90 day, genotype guided, warfarin dosing protocol. This dataset was annotated with standard MU terminologies, loaded, and transformed using the UMLS. We have deployed this methodology to scale in our in-house analytics platform using structured EHR data for 7931 patients  treated at the Froedtert Hospital. A demonstration limited to Clinical Avatars data is available on the Internet using the credentials user “jmirdemo” and password “jmirdemo”.Despite its inherent complexity, the UMLS can serve as an effective interface terminology for many of the clinical data standards currently used in the health care domain. The Health Information Technology for Economic and Clinical Health Act, enacted as part of the American Recovery and Reinvestment Act of 2009, introduced the concept of Meaningful Use (MU) of information technology in health care. The definition of MU in this context is complex and consists of several objectives and measures that health care providers have to demonstrate in three stages and within strict timelines in order to be eligible for early adopter incentives, and later on to avoid penalties for noncompliance starting in 2015. The MU legislation was designed to transform US health care through the development of processes and standards to capitalize on information in individual medical records and to create data resources that would result in better health care for the greater population.As part of this process, the legislation mandated the use of standard terminologies for the electronic exchange of health information. In particular, the Office of the National Coordinator for Health Information Technology defined a common set of MU data elements for which certification would be required across a number of electronic health records (EHR) interoperability certification criteria. The EHR interoperability can be further categorized into: 1) foundational, the ability to send information from one system to another, but without the need for interpretation on the receiving end; (2) structural, the syntax, format of simply messaging standards to provide transport of the information; and finally, the most challenging, (3) semantic interoperability, which allows the receiving system to interpret and integrate the received information [ foundatilingua franca of the clinical observation exchange with its more than 20,000 users in 150 countries [The Systematized Nomenclature of Medicine, Clinical Terms (SNOMED CT) is one of the most widely used biomedical terminologies in the world. It provides terms, synonyms, and relations covering a number of clinical domains including diseases, findings, and procedures . The Logountries . The Natountries . The RxNountries . It incoountries . The Ameountries , developountries . The IntUS health care relies on a number of different clinical terminology standards with varying levels of overlap and maturity. This already intricate landscape is further complicated by the disparity between billing and MU reporting. For example, SNOMED CT is not allowed in claims reporting and RxNorm combines multiple NDCs under one substance code, rendering detailed package and labeler based billing difficult. The clinical informatics community is now recognizing the need for new tools capable of consuming these heterogeneous resources, hence the term “next generation phenotyping” . In thisipso facto, add another layer of complexity to an already convoluted process.Many organizations develop their own local coding systems to address these challenges. In fact, to meet the 2014 Edition EHR Certification Criteria, providers are not required to use terminology standards internally as long as they are able to consume them for data portability and clinical quality measures reporting. Convergent Medical Terminology (CMT) is an example of such a solution developed by Kaiser Permanente (KP). CMT serves as the common terminology across all of the KP enterprise, and, at its core is comprised of SNOMED CT, LOINC, and First DataBank drug terminology . HoweverWe therefore propose a different solution that relies on the Unified Medical Language System (UMLS) developed and maintained by the National Library of Medicine (NLM) . All of There is now a significant need for integrating patient data from multiple sources, as well as supporting ontology driven querying and reporting on a large scale basis as the transformation of health care from paper to electronic progresses. The UMLS has been widely used as a terminology repository ,14, in oLightweight object models can rely on ontologies instead of modeling semantics explicitly. We have previously demonstrated this approach in the Observ-OM and VarioML models that were specifically validated for phenotype and genotype information by the GEN2PHEN  ConsortiAdditional semantic information can be derived from the semantic type of the UMLS concept used in the annotation. For example, the concept of Warfarin is typed in the UMLS Semantic Network as a Pharmacologic Substance. Thus, any observation about Warfarin can be inferred to be a medication for the purpose of querying or reporting. Where this is insufficient, we used explicit value sets. For example, the Common MU Dataset defines a set of SNOMED CT terms that together comprise smoking status see . In thisThe terminology service is built on top of a local database, which is populated with a standard set of vocabularies in the UMLS Active Release . The UMLS is loaded into an Oracle database 11g using the Structured Query Language (SQL) scripts provided with the UMLS distribution and updated in sync with its semiannual release cycle. The currently loaded version is displayed dynamically in the scorecard section of the project home page. As a reference, a 2013AB version set incorporating 89 UMLS terminologies included 2,805,252 unique concepts and 8,622,812 synonyms. RxNorm information is loaded as part of the UMLS distribution, rather than through its own separate release.For the sake of usability, only a preconfigured subset is displayed as navigable tabs at the top of the browser window  to optimize a dedicated NDC search, which does not exist otherwise as a term code in the concept table (MRCONSO). A label and synonym search was implemented using Oracle Text, a set of Oracle based tools for building text query and document classification applications that provides indexing and text classification capabilities. Individual text tokens are indexed using the term frequency, inverse of the document frequency algorithm, reflecting how often a particular string occurs in the UMLS .Rather than using a complex advanced search interface, we have a single search box that relies on the query relaxation approach . Dependi“rash on examination” and “rash” OR “on” OR “examination” to increase recall. Fuzzy and wildcard matching typically provide the most hits at the expense of precision (a fraction of retrieved instances that are relevant). However, as they are later in the query progression sequence, they are also ranked lower than exact matches, if such exist. For instance, two examples of such fuzzy queries are: (1) “cron disease” (typo in Crohn), which returns the following top three results- “Crohn Disease”, “Crohn's disease”, and “Crohn's disease of large bowel”; and (2) search for “myleoid leukemia” (typo in myeloid), which returns “Myeloid Leukemia”, “Primary Myelofibrosis”, and “Leukemia Myelocytic Acute”.Interpreting a query string using different operator combinations simultaneously allows for a more concise query design. For example, if a user enters a query “rash on examination”, the application can interpret the query in parallel as a single phrase An example of one of the more powerful features of the Oracle Text search is the ACCUMulate operator that allows parts of the query that did not match to be ignored. That means that it is not necessary to artificially restrain the number of keywords in a query. For example, searching for “cystic fibrosis gene carrier” returns “Cystic fibrosis gene carrier” , “Carrier of cystic fibrosis gene mutation” , “Encounter due to being a cystic fibrosis carrier” . In this case, only the first result matched the exact phrase, while the second result had all the keywords, but in a different order, and finally, the last result did not include the keyword “gene”.The exploration of the UMLS is challenging because of its complexity and lack of obvious starting points, typical of more formal classifications. The UMLS is often displayed as a tree of high level root concepts for the underlying terminologies (cf. the NLM browser provided by the UMLS Terminology Services), but it is in fact more of a tightly interwoven mesh, as it integrates multiple ontology sources with often overlapping coverage and different layers of granularity. Previously, it has been demonstrated that the UMLS is a scale free network that contains both noisy concept hubs  and informational concept hubs  .Additionally, a graph of UMLS size cannot be effectively analyzed using available state of the art network analysis software, for example, Cytoscape . For thi“dermatologic disorders” via “disorder of soft tissue”. Additionally, to augment relatively flat LOINC and RxNorm hierarchies, some other relations are treated here as hierarchical, for example “class_of” and “measured_by” in the case of LOINC. This can be seen in This MU 360 view is a custom UMLS perspective integrating all its sources with a specific focus on MU terminologies. For the purpose of hierarchical display and browsing, we adopted a conservative approach and limited the UMLS traversal to either the UMLS itself, or any of the following terminologies specific to MU- RxNorm, NDF-RT, LOINC, SNOMED CT, HCPCS, and ICD-9-CM. We explicitly ignore hierarchical relations from other terminologies, as in our experience they may add nonsensical paths to query expansion, for example, between “myocardial infarct” and An example of one of the unique features of mature terminologies such as SNOMED CT in contrast to more simple classification systems such as ICD-9, is that a single concept can exist in multiple places of the hierarchy, for example, “bronchitis” has two parent terms, “infection” and “bronchial disease”. This is difficult to display using a tree like hierarchy, as it requires multiple tree fragments. Instead, the ClinMiner terminology browser displays the active term, all of its parents, siblings, and children terms in three horizontally aligned panes at the same time. The Rat Genome Database originally introduced this approach . When a An automatic process translates original codes in patients’ EHR data to their corresponding UMLS concept unique identifiers (CUIs). To facilitate queries across thousands of patients, the transformation process also includes query expansion and complement creation. For example, a patient with “deep vein thrombosis” and “acute myocardial infarction” would, at this step, also be automatically annotated with “cardiovascular diseases”, the parent term for these two concepts, as well as negated “No past history of venous thrombosis” and “Myocardial perfusion normal”, when no annotations were made to these concepts for this patient. In addition to the intentional restrains on the UMLS traversal described earlier, query expansion is limited to concepts that are within the same UMLS Semantic Network , as shown in In terminologies that use multiple inheritance as a design pattern , a single term can exist in multiple paths. Additionally, different granularities and overlap across source terminologies lead to hierarchical cycles (loops). Patient level query expansion adds to this complexity as patients can have multiple annotations of the same type or varying levels of overlapping granularity (see the earlier example of “bronchitis” and “infection”). The simple addition of branch counts would in this case lead to inflated numbers. For this reason, sets of unique patient identifiers have to be propagated across the ontology graph to precalculate accurate patient level counts at every level of the ontological hierarchy, which would eliminate the aforementioned issues and produces a directed acyclic graph. From this, it is straightforward to calculate the propagated negated information as a relative complement of a set of propagated patient terms with respect to all propagated terms across all patients.In order to minimize the user effort involved in browsing large hierarchies, the ontology graph is additionally approximated as a minimum Steiner tree problem . This prThe application was developed in Java using enterprise Java technologies- Spring Framework, Spring Roo, Java Persistence Application Programming Interface , Apache Maven, and AspectJ Vaadin, a Java Web application framework that extends Google Web Toolkit, was used to provide the rich Internet application experience. Apache Tomcat provided the Web container. The Apache Hypertext Transfer Protocol Server isolates the Web container and forces encryption on all browser connections with 256-bit Transport Layer Security.Requests for a virtual machine image containing a preconfigured version of ClinMiner can be made to the corresponding author. We also welcome data submissions to our local instance, which can then be securely accessed over the Internet, so there is no need for additional deployment.To drive the initial implementation, we used simulated patient data kindly provided by the Clinical Avatars project . The Labas is.The Clinical Avatars data elements were manually mapped using MU ontologies. The mappings were than validated, and the final set is shown in A “Limited Dataset”, as defined under the Health Insurance Portability and Accountability Act, encompassing 7931 patients was obtained from the Medical College of Wisconsin Clinical Research Data Warehouse for this study. The data extract was in the form of standard Epic Clarity tables for a subset of patients that had an encounter or a problem list in the “Malignant neoplasm of pancreas” (ICD9:157) or “Epilepsy and recurrent seizures” (ICD9:345) code subset. Epic Clarity is an SQL relational database extracted for reporting purposes from Epic Chronicles, the data engine at the heart of Epic’s EHR.The drug information in the EHR was encoded using Medi-Span terminology, one of the RxNorm sources, which facilitated its automatic translation into the UMLS. The clinical results were encoded as orders using CPT-4 codes or using a fixed category from the “CLARITY_COMPONENT” lookup table. We have manually mapped the top 130 most frequently performed laboratory tests  to LOINC, which provided coverage for 94.07%  of all the laboratory tests. The remaining 5.93%  laboratory tests were left unmapped.A practical difference between simulated and real EHR data is the much larger concept space, which in this case covered 13,614 unique ICD-9, CPT-4, LOINC, and RxNorm codes. This code set was remapped into the UMLS, which resulted in 13,383 distinct UMLS CUIs, and then expanded as described previously across a limited set of “is_a” and selected other relationships  to facilitate querying, which produced the final set of 30,153 concepts. We have successfully applied this approach in a separate study focused on association rule mining in pancreatic cancer .A demonstration limited to Clinical Avatars data is available on the Internet using the credentials user “jmirdemo” and password “jmirdemo” .The crosswalk via the UMLS between different terminologies, as demonstrated in The extract, load, and transform approach is substantially different from a more common extract, transform, and load approach, when data is transformed before it is loaded into the data warehouse. Conversely, with extract, load, and transform, we essentially maintain two versions of data: (1) the original annotation set made in the EHR, and (2) a dynamically generated set of UMLS mappings. The original data is never lost, and can be retransformed as new knowledge becomes available.We are now working on expanding the transformed information to include date and values to support more advanced temporal and value restricted queries. This is a critical step that has a significant impact on the time required to query patient information, however, the actual transformation is relatively resource consuming, for example, it creates 238 annotations per avatar using simulated data and several thousand annotations per patient with real EHR data.A relatively large number of concepts remain unused when annotating clinical data to large terminologies. The UMLS, the largest repository of biomedical terminologies, in its current version spans over 10 million unique concept names from over 160 source vocabularies. Only a subset of the UMLS might be suitable for concept matching , and SNOWhile physicians rarely have to deal with ontology hierarchies directly, these are indispensable in clinical research to facilitate query expansion, building transitive closures, and data validation and reconciliation. Any sufficiently large terminology is likely to suffer from some inconsistencies and these, however minor, present unique challenges for ontology end users when they have no direct control over the terminologies they are using. With hundreds of thousands of concepts, traditional navigation through terminology hierarchies becomes impractical. This is why we put a special focus on enhancing search capabilities as well as providing data-driven perspectives that dynamically hide some of this complexity. The search becomes even more important when concepts do not appear where expected or are not in hierarchical relations at all. In our experience, this is the case in approximately one third (data not shown) of LOINC and RxNorm concepts.Current requirements for terminology standards are not necessarily intuitive and are likely to cause confusion among implementers and subsequent interoperability issues. Optionality for some of the vocabulary standards only adds to the confusion. Existing studies suggest that there is a wide variation in accuracy of MU electronic reporting . Even wiInterestingly, several resources in the genotype to phenotype space now actively map to the UMLS directly: (1) Orphanet, a portal for rare diseases ; (2) theThe UMLS incorporates decades of experience and consistency represented by the US National Library of Medicine, which in fact already maintains RxNorm, one of the MU terminologies. It is therefore not unfeasible that the UMLS could provide a clearer path to semantic interoperability.Despite its inherent complexity, the UMLS can serve as an effective interface terminology for many of the clinical data standards currently used in the health care domain.


The cellular form, manifesting as a membrane-bounded system , is essential to life. The ultimate reason for this is that, typically, one functional molecule can only adopt one “correct” structure to perform one special function , and thus molecular cooperation is inevitable. While this is particularly true for advanced life with complex functions, it should have already been true for life at its outset with only limited functions, which entailed some sort of primitive cellular form—“protocells”. At the very beginning, the protocells may have even been unable to intervene in the growth of their own membrane, which can be called “pseudo-protocells”. Then, the ability to synthesize membrane components (amphiphiles) may have emerged under selective pressure, leading to “true-protocells”. The emergence of a “chromosome” (with genes linked together)—thus avoiding “gene-loss” during the protocell division, was another key event in the evolution of protocells. Such “unitary-protocells”, containing a central genetic molecule, may have appeared as a milestone—in principle, since then life could evolve endlessly, “gaining” more and more functions by introducing new genes. To synthesize in laboratory these different types of protocells, which stand at the interface between life and non-life, would greatly enhance our understanding on the essence of life. Cells are fundamental to life nowadays. All living things are made up of cells, except for viruses, which, though capable of existing “physically” independent of cells, are only “biologically” active within host cells: but why? A general answer is that living activities are based on the cooperation of molecules, and lipid vesicles, which are bounded by amphiphilic membranes in water, provide the most effective form in nature for such cooperation. However, to provide a more exact answer we need a more detailed analysis. Does life really have to be implemented by the cooperation of molecules? Moreover, if yes, how about other forms for such molecular cooperation? In the following, we will see that such an analysis would lead us to inquire into the very early stages of life.Though there is no consensus on a definition for life, there is no doubt that life is something capable of Darwinian evolution ,2,3. Thevice versa. However, even if such an extreme scenario involving intramolecular action was possible in the very beginning of life, it was not possible for the life later—perhaps already impossible only a short time later when a second function appeared. Can one imagine a large RNA molecule with quite a few domains to implement different functions respectively? In other words, even if the two key features, genetic and functional, could be implemented on a single molecule at the very beginning , when life evolved forwards and different functional molecules  emerged, the cooperation between molecules would have become inevitable. For the topic about the arising of life from non-life, the RNA world hypothesis helps to sidestep the “which came first, DNA or protein?” dilemma in the context that both the genetic feature and the functional feature are indispensable for life. Regarding the topic here, it means that the cooperation of “two types of molecule” could be “avoided” in life. Moreover, it has even been postulated that the RNA world might have begun with some kind of “RNA replicase” (ribozyme), which can exhibit both those two key features by catalyzing its own replication ,9,10. ThThe key point is: a functional molecule (either a protein or an RNA) typically has only one function . Therefore, given that more and more functions would emerge through evolution, more and more functional molecules would become involved in the living activities of organisms. Indeed, molecular cooperation would not only be indispensable but also become more and more complicated.Then, obviously, there is a problem of spatial limitation—in which way could these molecules be kept sufficiently close to each other to ensure such cooperation? Several ways have been proposed for such spatial limitation at an early stage. One way is by the adsorption of mineral surface. For example, the RNA world, with its cooperative molecules, is speculated to have begun on the surface of minerals such as montmorillonite and hydroxylapatite ,14,15,16Mycoplasma genitalium, which has approximately 470 (protein-coding) genes [Tremblaya princeps PCVAL which has still 116 genes [Nasuia deltocephalinicola, which itself has 137 genes [Modern cells are very complicated. The simplest free-living organism/cell in nature known to date is g) genes . Starting) genes ,36,37. I16 genes  (Note: i37 genes ). As men37 genes ,30,40,41As it was stated, though there are as yet a number of obstacles for the RNA world hypothesis, it remains the best, central idea in our efforts to interpret the origin of life . Accordii.e., protocells, may have evolved. We rely heavily on the RNA world hypothesis because to date it is the only idea put forth that does not evade the question of how Darwinian evolution could have got start, which is associated with the topic here—the interface of life and non-life. If the following discussion, which adopts the notion of the RNA-based protocell, appears to be delineating a detailed scenario, one should keep in mind that it just represents one speculation regarding the early stage in the origin of life. For example, if there was some “pre-RNA world(s)” that used RNA-like molecules as genetic and functional material [Whether or not the lipid vesicle containing the RNA replicase can represent the simplest cellular form, the notion of the RNA-based protocell serves well as a “working concept” for us to examine some fundamental issues concerning the primitive cellular form. As we will see in the analysis, we can define different stages for the protocells. Note that here our main aim is to deduce how the primitive cellular form, material ,10, the material ,26, the i.e., the duplication of the molecules therein, and then the fission. For modern cells, both growth and fission are well controlled, involving many genes/functions. However, for those simplest protocells, which comprise few genes/functions, how could these be carried out? Primordially, the division of a protocell may have occurred spontaneously, i.e., by physical mechanisms, when it grows to an unstable level [First, let us look into the “reproduction” of the protocells. Reproduction is a prerequisite for Darwinian evolution. If a single molecule is deemed as a “living unit” , its replication is just such “reproduction”. However, the reproduction of a molecular assembly like that in a cellular form is no doubt more complex. It includes the growth of the “molecular assembly”, le level ,51. The In a distinctive study, it was observed that fatty acid vesicles encompassing RNA molecules were more swollen (under the osmotic pressure) and would grow to a larger size by sacrificing empty vesicles, which were more relaxed    Figure A. Howeveetc. However, this so-called “bag of genes” faced a problem [A true-protocell may have contained a few different functional RNAs, e.g., an RNA replicase, a ribozyme catalyzing the synthesis of nucleotides, a ribozyme catalyzing the synthesis of membrane components,  problem  when the problem ,56. When problem .i.e., the ribozymes) from the chromosome would have become problematic. In a recent paper, inspired by features of viroids [However, there would have been quite a few difficulties for the emergence of the primordial chromosome, e.g., the RNA chromosome would have been much longer than single RNA genes and hence run a greater risk of degradation (chain breaking) before completing replication; the copying of the chromosome may have started at sites in the middle of the chain, resulting in a partial replication; without a complex transcription mechanism , the synthesis of distinct gene products . In a word, typically one sequence has one function because typically one sequence has one structure and typically one structure has one function. Indeed, molecular cooperation was inevitable only if more functions “ought to” appear in evolution. Fortunately, also in this physico-chemical world, amphiphilic molecules can assemble to form vesicles in water, providing a simple and effective way to ensure such molecular cooperation.On the genetic feature aspect, which is realized via the template-directed replication by the “base-pairing mechanism”, there is no serious problem to accommodate more functions, because different “genes” may be replicated sequentially in the same manner in a single larger molecule. However, on the functional feature aspect, which is realized by the folding of the functional polymer into a special structure, things are completely different. As mentioned above, a functional molecule typically carries out only one function. We could not imagine a large functional molecule (either RNA or protein) with a number of domains to implement a number of different functions respectively. Moreover, we could not expect one functional polymer, either RNA or protein, to be capable of carrying out many different tasks in different circumstances respectively. These are based on the constraints imposed by the physico-chemical rules governing the folding of the macromolecules in water. It is unlikely that the different domains in that large functional molecule could fold into their “correct” structures without interfering with each other, and a functional molecule with a definite sequence could not have different “correct” structures , we may feel that we obtain a “snapshot” concerning the starting point of real life.A logical way to deal with this challenge is to investigate the interface between life and non-life, which by definition, is relevant to the field of the origin of life. According to our analysis here, at the outset of life, spatial limitation to ensure molecular cooperation was already quite significant when there were only limited functions, and protocells likely emerged rather early. In other words, it was just the protocells that stood at this interface. However, because the origin of life, as a historical process that occurred in the remote past, bears predestined uncertainties, we should pay more attention to the scientific aspect, which pursues repeatable facts and relevant rules . So a go


Survivorship is a complicated notion because people often confuse a process of survivorship with a mythic identity of being a cancer survivor. This confusion may be a distraction to addressing the real-life struggles and challenges experienced by all people diagnosed with cancer. A more expansive perspective of survivorship, one that attends to patients’ physical, psychological, social, spiritual, and existential challenges throughout a continuum of care, would be more in line with what is known empirically about people’s experiences with cancer. In an effort to gain a patient-centered perspective on cancer, and one that emphasizes multiple dimensions of cancer survivorship, the author reports findings from a non-scientific social media poll  in which survivors and colleagues working in the field of cancer survivorship answered the question: What does cancer survivorship mean to you? The comments are enlightening and useful for guiding the development of a patient-centered, and, thus, more comprehensive, approach to caring for people affected by cancer. Regardless of the type of cancer or the extent of survival, all persons diagnosed with cancer must manage the enduring and complex ways in which cancer transforms the self and everyday life .There was a time when “cancer survivors” were considered the family members, friends and loved ones left behind when someone died of cancer. Today, “cancer survivors” refers to the nearly 14 million individuals in the US who themselves are alive after a cancer diagnosis.In 2005, the Institute of Medicine emphasized the importance of attending to the lives and quality of life of cancer survivors .In an effort to gain a patient-centered perspective on cancer, and one that emphasizes the psychological, social, and experiential aspects of cancer survivorship, I conducted my own social media poll of friends and colleagues by asking them via Facebook and personal email: What does cancer survivorship mean to you? The comments are enlightening, and I believe useful, for guiding the development of a patient-centered, and thus more comprehensive, approach to caring for people affected by cancer..Survivorship is a complicated notion because people often confuse the process of survivorship with the mythic identity of being a cancer survivor. Indeed, Dr. Pamela Leung, Professor of Social Work at Hong Kong University, reported: “There is no Chinese translation for the word ‘survivor.’ As more and more people live longer with incurable cancer, or after remission, for substantial periods of time, I think cancer survivorship should not be restricted to those who have their cancer cured” .The National Cancer Institute’s (NCI) Office of Cancer Survivorship states that “an individual is considered a cancer survivor from the time of diagnosis, through the balance of his or her life.” This definition identifies a specific population with its own unique needs and experiences, and also suggests that survivorship challenges and quality of life issues initiate at the time of diagnosis and occur throughout a continuum of care. However, it also confounds an identity—being a cancer survivor—with a medical condition and social phenomenon—an experience of living with cancer. People with cancer have varied and complex feelings of whether or not they feel they are “survivors”.NCI’s definition of a cancer survivor contrasts with the research portfolio it holds and supports, which focuses solely on a post-treatment phase. This apparent contradiction is evidence that the terms “survivor” and “survivorship” are fraught with ambiguity and require further clarity and theoretically-derived meaning. The confusion may be a distraction to addressing the real-life struggles and challenges experienced by all people diagnosed with cancer.Lacking cogent definition and theory that distinguishes “survivor” from “survivorship” has led some patients into feeling pigeon-holed into an identity that does not accurately reflect their experience and to which they cannot relate. In spite of a growing movement and number of cancer survivors, many health care providers, as well as patients, do not like the term. Says long-time oncology social work leader, Dr. James Zabora: “I have never really like this term. I believe that survivor has a negative connotation and creates the image of a long-term and difficult struggle. It is as though we had to create another field of practice. I have always favored approaches such as ‘a life with cancer’ or ‘living with cancer’ because I think these terms are more positive and accurate” .As described by self-proclaimed cancer survivor and oncology social worker Richard Dickens, “Survivorship is a paradoxical word eliciting a myriad of meanings, including pride, uncertainty, safety, guilt, good fortune, gratitude, hope, and perhaps the most real and yet most unspoken, not dead. Each of these meanings, like cancer, elicits a myriad of feelings, physically and emotionally” . Mr. DicSurvivorship is NOT simply about being or feeling like a cancer “survivor”. In caring for people with cancer, we must avoid what Heidi Adams, founder of Planet Cancer and Chief Executive Office for Critical Mass, calls the “semantic minefield” of survivorship, which fails to distinguish identity from life experience. A more expansive perspective of survivorship would be more in line with what is known empirically, that early experiences have life-long repercussions. Thus, survivorship care would require expanded attention to patients’ physical, psychological, social, spiritual, and existential challenges throughout a continuum of care. Its goal would be the minimization of long-term debilitation, but also the facilitation of patient coping and adaptation, and perhaps even the promotion of personal transformation and growth.To talk about cancer survivorship broadens the context for understanding how cancer affects people’s lives, attitudes, and behaviors, and how best to attend to them. Indeed, “Survivorship” can become a framework upon which to build, test, enhance, and reinforce systems of cancer care . It reflA patient-centered perspective on survivorship was first articulated, and probably best epitomized, by Susan Leigh, an oncology nurse, three-time cancer survivor, and founding member of the National Coalition for Cancer Survivorship. She was the first to suggest that cancer survivorship is about “living with, through, and beyond cancer” . This deRiding the bus to and from medical appointments.Waiting in long lines, sometimes all day without being seen by a medical provider.Not getting the care you need because you cannot afford to pay for the costs of care.Making a choice to see a physician even though you fear being deported.Remaining silent when you should speak up because you feel no one really understands you.Facing cancer alone because family members are too worried about losing their job if they spend any time away from work.Doing whatever it takes to stay alive and be on this earth for your children.Social work researcher Dr. Frances Nedjat-Haiem, PhD, offers a patient-centered view of survivorship based on her research involving observations and interviews with underserved and disadvantaged low-income Latino cancer patients in Los Angeles. According to Dr. Nedjat-Haiem, cancer survivorship means : Riding Les Gallo-Silver, long-time oncology social worker and Associate Professor of Health Sciences, described survivorship as “a process of retaining control of one’s life after the diagnosis, making informed decisions about treatment, adapting to changes in daily routines, and developing strategies to manage temporary and perhaps permanent physical changes. Survivorship is not letting cancer define you even as it changes you. Survivorship can be emotionally centering and energize a sense of purpose and an altered direction in one’s life. Medicine may measure survival in weeks, months or years from diagnosis, yet the human spirit measures survival in experiences to be appreciated and intimacies to be cherished” .Oncology social worker Pat Fobair suggested that survivorship is about “[L]earning to look at life in new ways. It is about forgiving friends and family who don’t come through for us, looking at the meaning in life from different perspectives, deciding how you want to proceed, making new plans, opportunities, relationships” .Living is a process. Living with cancer is a process. What happens in early phases of diagnosis and treatment influence later life experiences? Behavioral scientist and quality of life researcher Carolyn Gotay, PhD, suggests that cancer survivorship is “a constantly shifting landscape, not limited to people who are cancer-free or to people who have completed cancer treatment, and involves others beyond the person who has had a cancer diagnosis” .From the point of view of caregivers and loved ones, survivorship is about gratitude and relief, but also fear and disappointment, and how the experience is life-altering for them, as well. Examples of these viewpoints follow:“It means growing up with a mother! My mom had breast cancer when I was 5 years old. I remember my grandmother taking care of us when she was sick, and her having to wear a wig. She survived and is now 74. I guess you can say my kids have a grandmother, too” [“It has meant more years with a dear friend” .“The fear experienced by me as a caregiver and daughter to my mother with her diagnosis of lung cancer had me wailing and rolling on the floor of my bedroom. Not something I had ever done or have done since” .Articulating the difference between “survivorship” and “being a survivor” can distinguish a process of living from a state of being or identity. From diagnosis until one’s final breath, individuals with cancer are in a process of survivorship—living with cancer. How different our approach to oncology care, including end-of-life care, might be if we were to integrate survivorship into conventional approaches to clinical care, where both patients and providers meet and negotiate mutual interests and therapeutic goals. Elevating the needs, values, and preferences of patients and their families can only lead to the achievement of greater patient participation in their own care, enhanced mutual decision-making and service delivery, and improved patient outcomes. As for defining who or what is a survivor, perhaps that definition should be left solely to each individual living with cancer.


Schizotypy is the notion that schizophrenia-like features can form, in the absence of illness, a temperamental “type” or personality trait. Both typological and characterological accounts were present at the notion’s conception as, historically, both categorical (“Kraepelinian”) and dimensional  accounttheory and methodology. I aim to argue here based on four observations of the empirical literature that aspects of both theoretical accounts may be valid, and that a diversity of methods may have utility in the field.In 1995, Adrian Raine and Todd Lencz  set out underlying dimensionality of risk for illness with superimposed clinical discontinuities – the schizophrenic “spectrum” of illnesses. The critical difference between the two accounts of schizotypy lies in the non-clinical portion of the phenotype. In the categorical account, only a portion of phenotypic schizotypy is at genuine elevated risk, the “true” schizotype, the remainder is pseudophenotypic, superficially mimicking schizotypy but not possessing true genetic risk: Adrian Raine . Large samples are required if the truly taxonomic approach is to be taken in a multivariate analysis. While this suits some fields such as quantitative genetics, it is not suited to others such as brain imaging. On the other hand, a common strategy is to preselect “schizotypal” and “non-schizotypal” groups via large-scale screening using a psychometric instrument. This usefully reduces the number needed to test experimentally to achieve statistical power. However, the strategy may or may not imply testing of a categorical model – it is also, of course, a strategy of convenience for testing dimensional differences.both may have validity and research utility (and I do not claim that this is an exhaustive list).As a consequence of all these considerations, I would argue that while genuine differences clearly exist between the models theoretically, these are very rarely tested against one another genuinely at the empirical level. Evidence can be found (and is often rehearsed) for both categorical and dimensional positions – even from the same dataset. In some ways, this apparent duality may parallel the famous “wave–particle” duality of quantum theory that suggests that both accounts can be “true” in different ways, and thus seeks to explain a diverse range of observations. At the crudest level, one can observe that broad measurement of trait tendencies tend to produce continua, and narrow “symptom-focused” measures lead to categories. I would like to suggest some important ways that per se as too narrow a lens, “psychosis proneness” captures the variety of traits relevant to psychotic disorders as a whole.I am not alone in noticing empirical evidence for both positions . From reRegardless of psychometric arguments about putative taxons, it is likely that some measures suit one theoretical position better than another. Those with “stronger” symptom-like measures may tend to discontinuities, while others offer greater dimensionality. In addition, even the range and nature of dimensions of schizotypal personality are argued over, with perhaps the broadest consensus concerning a distinction between positive and negative schizotypy. Arguably, there are stronger indications for the taxonomic nature of negative schizotypal features such as trait anhedonia [for review see Ref. ]. ConverIn a development of this first point, Suhr and Spitznagel , 12 atteWhile personality traits are usually seen as broadly consistent over time, stress or other unusual circumstances produce “state” effects that may possess qualitatively different, and thus discontinuous, features. In this way, traits may proceed, more or less temporarily, to “symptoms” in the absence of a diagnosed syndrome. Usually these are probably highly temporary, but where more persistent or frequent that they effectively form sub-syndromal versions of disorders such as “basic symptoms” captured by the Schizophrenia Proneness Instrument . These sprima facie grounds, such evidence supports the notion of one or more continua (It is increasingly accepted that many individual loci each make a very small contribution to overall genetic risk . On primcontinua , 17 and continua , albeit continua ] postulacontinua ]. A smalcontinua , 21, DRDcontinua , SLC6A3 continua , 21, or continua . Such stcontinua . As invebut only in the context of a pathogenic environment.There is also increasing evidence of epigenetic action, whereby environmental factors influence the expression of genes , 24. Svaeven in the non-pathological domain of schizotypal individual differences there are numerous possibilities for both dimensional and categorical expressions both of traits and states. Taxonomic expression has greater support for negative schizotypal features such as anhedonia and potentially some associated neurocognitive features; positive schizotypy, on the other hand, sees much empirical support for “true” dimensionality at both genotype and phenotypic expression. Even here, however, there is room for gene–environment interactions and epigenetics to produce discontinuous results.Overall, I have attempted to argue that As a rider to this final point, it is apposite to point out that there may equally be important phenotypic consequences for schizotypy in the absence of a pathogenic environment or the presence of a protective factor such as high cognitive or emotional intelligence. Thus, positive schizotypy is also associated with a range of “healthy” or at least adaptive outcomes. Again, paralleling the advantages seen with cluster analytic approaches, Tabak and Weisman de Mamani  identifiThe author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.