Cultural concepts of distress and complex PTSD: Future directions for research and treatment

Complex post-traumatic stress disorder (CPTSD) was introduced as a new diagnostic category in ICD-11. It encompasses PTSD symptoms along with disturbances in self-organisation (DSO), i.e., affect dysregulation, negative self-concept, and disturbances in relationships. Quantitative research supports the validity of CPTSD across different cultural groups. At the same time, evidence reveals cultural variation in the phenomenology of PTSD, which most likely translates into cultural variation with regard to DSO. This theoretical review aims to set the ground for future research on such cultural aspects in the DSO. It provides a theoretical introduction to cultural clinical psychology, followed by a summary of evidence on cultural research related to PTSD and DSO. This evidence suggests that the way how DSO symptoms manifest, and the underlying etiological processes, are closely intertwined with cultural notions of the self, emotions, and interpersonal relationships and interpersonal relationships. We propose directions for future research and implications for culturally sensitive clinical practice

A survey of the elementary principal's professional library in 135 selected schools of Massachusetts.

Thesis (M.A.)--Boston Universit

Cultural concepts of distress and complex PTSD: Future directions for research and treatment

Complex post-traumatic stress disorder (CPTSD) was introduced as a new diagnostic category in ICD-11. It encompasses PTSD symptoms along with disturbances in self-organization (DSO), i.e., affect dysregulation, negative self-concept, and disturbances in relationships. Quantitative, etic research, which applies the same constructs and measures across cultural groups from an “outsider” perspective, supports the cross-cultural validity of CPTSD. At the same time, evidence from qualitative, emic research, which takes the viewpoint of the “insider,” reveals cultural variation in the phenomenology of PTSD, which most likely translates into cultural variation regarding DSO. This theoretical review aims to set the ground for future research on such cultural aspects in the DSO, by proposing a balanced, complementary use of etic and emic research. Evidence from etic and emic research related to PTSD and DSO suggests that the way that DSO symptoms manifest, and the underlying etiological processes, are closely intertwined with cultural notions of the self. We argue that it is important to consider potential variations in normative cultural scripts related to the self, emotion regulation and interpersonal relationships across cultures to better understand how DSO symptomatology deviates from such normative scripts. We propose directions for future research and implications for culturally sensitive clinical practice

Polytraits : a database on biological traits of marine polychaetes

The study of ecosystem functioning – the role which organisms play in an ecosystem – is becoming increasingly important in marine ecological research. The functional structure of a community can be represented by a set of functional traits assigned to behavioural, reproductive and morphological characteristics. The collection of these traits from the literature is however a laborious and time-consuming process, and gaps of knowledge and restricted availability of literature are a common problem. Trait data are not yet readily being shared by research communities, and even if they are, a lack of trait data repositories and standards for data formats leads to the publication of trait information in forms which cannot be processed by computers. This paper describes Polytraits (http://polytraits.lifewatchgreece.eu), a database on biological traits of marine polychaetes (bristle worms, Polychaeta: Annelida). At present, the database contains almost 20,000 records on morphological, behavioural and reproductive characteristics of more than 1,000 marine polychaete species, all referenced by literature sources. All data can be freely accessed through the project website in different ways and formats, both human-readable and machine-readable, and have been submitted to the Encyclopedia of Life for archival and integration with trait information from other sources

A marine biodiversity observation network for genetic monitoring of hard-bottom communities (ARMS-MBON)

Marine hard-bottom communities are undergoing severe change under the influence of multiple drivers, notably climate change, extraction of natural resources, pollution and eutrophication, habitat degradation, and invasive species. Monitoring marine biodiversity in such habitats is, however, challenging as it typically involves expensive, non-standardized, and often destructive sampling methods that limit its scalability. Differences in monitoring approaches furthermore hinders inter-comparison among monitoring programs. Here, we announce a Marine Biodiversity Observation Network (MBON) consisting of Autonomous Reef Monitoring Structures (ARMS) with the aim to assess the status and changes in benthic fauna with genomic-based methods, notably DNA metabarcoding, in combination with image-based identifications. This article presents the results of a 30-month pilot phase in which we established an operational and geographically expansive ARMS-MBON. The network currently consists of 20 observatories distributed across European coastal waters and the polar regions, in which 134 ARMS have been deployed to date. Sampling takes place annually, either as short-term deployments during the summer or as long-term deployments starting in spring. The pilot phase was used to establish a common set of standards for field sampling, genetic analysis, data management, and legal compliance, which are presented here. We also tested the potential of ARMS for combining genetic and image-based identification methods in comparative studies of benthic diversity, as well as for detecting non-indigenous species. Results show that ARMS are suitable for monitoring hard-bottom environments as they provide genetic data that can be continuously enriched, re-analyzed, and integrated with conventional data to document benthic community composition and detect non-indigenous species. Finally, we provide guidelines to expand the network and present a sustainability plan as part of the European Marine Biological Resource Centre (www.embrc.eu).Peer reviewe

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response