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Abstract Cancer of unknown primary (CUP) is an obscure disease characterized by multiple metastases in the absence of a primary tumor. No consensus has been reached whether CUPs are simply generated from cancers that cannot be detected or whether they are the manifestation of a still unknown nosological entity. Here, we report the complete expression and genetic analysis of multiple synchronous metastases harvested at warm autopsy of a patient with CUP. The expression profiles were remarkably similar and astonishingly singular. The whole exome analysis yielded a high number of mutations present in all metastases (fully shared), additional mutations (partially shared) accumulated one after another in a series, and few private mutations were unique to each metastasis. Surprisingly, the phylogenetic trajectory linking CUP metastases was atypical, depicting a common “stream”, sprouting a series of linear “brooks”, at variance from the extensive branched evolution observed in metastases from most cancers of known origin. The distinctive genetic and evolutionary features depicted suggest that CUP is a novel nosological entity.

Cancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor. Clinically, CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, an aggressive clinical course, poor response to empiric chemotherapy and, consequently, a short life expectancy. Two opposing strategies to change the dismal prognosis for the better are pursued. On the one hand, following the traditional tissue-gnostic approach, more and more sophisticated tissue-of-origin (TOO) classifier assays are employed to push identification of the putative primary to its limits with the clear intent of allowing tumor-site specific treatment. However, robust evidence supporting its routine clinical use is still lacking, notably with two recent randomized clinical trials failing to show a patient benefit of TOO-prediction based site-specific treatment over empiric chemotherapy in CUP. On the other hand, with regards to a tissue-agnostic strategy, precision medicine approaches targeting actionable genomic alterations have already transformed the treatment for many known tumor types. Yet, an unmet need remains for well-designed clinical trials to scrutinize its potential role in CUP beyond anecdotal case reports. In the absence of practice changing results, we believe that the emphasis on finding the presumed unknown primary tumor at all costs, implicit in the term CUP, has biased recent research in the field. Focusing on the distinct clinical features shared by all CUPs, we advocate adopting the term primary metastatic cancer (PMC) to denominate a distinct cancer entity instead. In our view, PMC should be considered the archetype of metastatic disease and as such, despite accounting for a mere 2–3% of malignancies, unraveling the mechanisms at play goes beyond improving the prognosis of patients with PMC and promises to greatly enhance our understanding of the metastatic process and carcinogenesis across all cancer types.

Abstract In the original version of this article [1], published on 2 September 2016, the name of author ‘Alice Balderacchi’ was wrongly displayed. In this Erratum the incorrect name and correct name are shown. The original publication of this article has been corrected.

Experiencing traumatic events is unfortunately commonplace and, in some cases, may lead to the onset of debilitating mental health disorders, such as post-traumatic stress disorder (PTSD). Current diagnostic criteria for PTSD results in high depression and anxiety comorbidity. Better understanding of biological mechanisms and pathways underlying PTSD could aid in more accurate case identification and stratification of treatments. Recent meta-analysis has identified chronic PTSD to be associated with increased expression of pro-inflammatory cytokines and alterations in neuronal structures which contribute to an overall reduction in brain volume. Despite this, there are currently no biological markers in clinical use to identify PTSD or monitor treatment. This case-control study (n = 40) aimed to identify differences in peripheral blood biomarkers, and biomarker combinations, able to distinguish PTSD participants from controls, and examine in a biopsychosocial framework. The levels of 5/37 biomarkers investigated were significantly altered in the serum of PTSD participants: HDL and LDL cholesterol, tPA, IL-8 and EGF. Biomarkers could be used in combination with psychological criteria, in a biopsychosocial model, to support clinical management decisions and ensure appropriate individual treatment pathways.

Background: Motivation and engagement are important factors associated with therapeutic outcomes in cognitive training for schizophrenia. The goals of the present report were to examine relations between objective treatment engagement (number of sessions attended, amount of homework completed) and self-reported motivation (intrinsic motivation and perceived competence to complete cognitive training) with neurocognitive and functional outcomes from cognitive training. Methods: Data from a clinical trial comparing two cognitive training approaches in schizophrenia-spectrum disorders were utilized in the current report (n = 38). Relations were examined between baseline intrinsic motivation, perceived competence, homework completion, and session attendance with improvements in neurocognition, functional competence, and community functioning. Results: Number of sessions attended (r = 0.38) and time doing homework (r = 0.51) were significantly associated with improvements in neurocognition. Homework completion was associated with change in community functioning at a trend-level (r = 0.30). Older age was associated with greater treatment engagement (β = 0.37) and male biological sex was associated with greater self-reported motivation (β = 0.43). Homework completion significantly mediated the relationship between session attendance and neurocognitive treatment outcomes. Conclusions: Objective measures of treatment engagement were better predictors of treatment outcomes than subjective measures of motivation. Homework completion was most strongly related to treatment outcomes and mediated the relationship between session attendance and treatment outcomes, suggesting continued engagement with cognitive stimulation may be an especially important component of cognitive remediation programs. Future research should examine methods to improve homework completion and session attendance to maximize therapeutic outcomes.

Introduction Over 30% of Canadians between the ages of 16 and 24 years attend university. This period of life coincides with the onset of common mental illnesses. Yet, data to inform university-based mental health prevention and early intervention initiatives are limited. The U-Flourish longitudinal study based out of Queen’s University, Canada and involving Oxford University in the UK, is a student informed study funded by the Canadian Institute for Health Research Strategy for Patient Oriented Research (CIHR-SPOR). The primary goal of U-Flourish research is to examine the contribution of risk and resiliency factors to outcomes of well-being and academic success in first year students transitioning to university.Methods and analysis The study is a longitudinal survey of all first-year undergraduate students entering Queen’s University in the fall term of 2018 (and will launch at Oxford University in fall of 2019). In accordance with the CIHR-SPOR definitions, students represent the target population (ie, patient equivalent). Student peer health educators were recruited to inform the design, content and implementation of the study. Baseline surveys of Queen’s first year students were completed in the fall of 2018, and follow-up surveys at the end of first year in the spring of 2019. Extensive student-led engagement campaigns were used to maximise participation rates. The baseline survey included measures of personal factors, family factors, environmental factors, psychological and emotional health, and lifestyle factors. Main outcomes include self-reported indicators of mental health at follow-up and mental health service access, as well as objective measures of academic success through linkage to university administrative and academic databases. A combination of mixed effects regression techniques will be employed to determine associations between baseline predictive factors and mental health and academic outcomes.Ethics and dissemination Ethical approval was obtained by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (HSREB) (#6023126) at Queen’s University. Findings will be disseminated through international and national peer-reviewed scientific articles and other channels including student-driven support and advocacy groups, newsletters and social media.

El presente ensayo da cuenta de un ejercicio de cartografía de la proximidad referente al tema del cuerpo como territorio. Con base en la historia de vida de una mujer salvadoreña, se pretende identi car la percepción que ella tiene sobre su cuerpo a la luz de seis categorías: trabajo, familia, actividades domésticas, actividades de cuidado, vulnerabilidad y autocuidado. Además, se contrastará esta percepción con relación a dos categorías más: el municipio de vivienda (Ahuachapán y San Salvador) y la época de la historia (conflicto armado y posguerra).

The present study investigates whether sport activities involving children with a disability can reduce negative attitudes towards disability in children without disability. We compared the effect of being schoolmate or member of the same football team whereby a child with disability was member of the class/team or not. This lead to four groups that were assessed both at the beginning and at the end of the school year. Two measures were collected: an ad-hoc questionnaire and an Implicit Association Test. The two assessments were designed to measure explicit and implicit attitudes towards children with disabilities. Results suggested that sport activities over one school year reduced more (p < .001) the implicit negative attitude towards disability (Mean = -.17, sd = .10) than the contact with the classmate in the school context (Mean = -.03, sd = .14), possibly due to their team building characteristic.