The role of insight, social rank, mindfulness and self-compassion in depression following first episode psychosis

Gaining awareness of psychosis (i.e., insight) is linked to depression, particularly in the post-acute phase of psychosis. Informed by social rank theory, we examined whether the insight–depression relationship is explained by reduced social rank related to psychosis and whether self-compassion (including uncompassionate self-responding [UCS] and compassionate self-responding [CSR]) and mindfulness buffered the relationship between social rank and depression in individuals with first episode psychosis during the post-acute phase. Participants were 145 young people (Mage = 20.81; female = 66) with first episode psychosis approaching discharge from an early psychosis intervention centre. Questionnaires and interviews assessed insight, depressive symptoms, perceived social rank, self-compassion, mindfulness and illness severity. Results showed that insight was not significantly associated to depression and thus no mediation analysis was conducted. However, lower perceived social rank was related to higher depression, and this relationship was moderated by self-compassion and, more specifically, UCS. Mindfulness was related to depression but had no moderating effect on social rank and depression. Results supported previous findings that depressive symptoms are common during the post-acute phase. The role of insight in depression for this sample is unclear and may be less important during the post-acute phase than previously considered. Supporting social rank theory, the results suggest that low perceived social rank contributes to depression, and reducing UCS may ameliorate this effect. UCS, social rank and possibly mindfulness may be valuable intervention targets for depression intervention and prevention efforts in the recovery of psychosis

Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions

<p>Abstract</p> <p>Background</p> <p>Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually<abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells.</p> <p>Results</p> <p>A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation.</p> <p>Conclusion</p> <p>Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.</p

New onshore insights into the role of structural inheritance during Mesozoic opening of the Inner Moray Firth Basin, Scotland

The Inner Moray Firth Basin (IMFB) forms the western arm of the North Sea trilete rift system that initiated mainly during the Late Jurassic–Early Cretaceous with the widespread development of major NE–SW-trending dip-slip growth faults. The IMFB is superimposed over the southern part of the older Devonian Orcadian Basin. The potential influence of older rift-related faults on the kinematics of later Mesozoic basin opening has received little attention, partly owing to the poor resolution of offshore seismic reflection data at depth. New field observations augmented by drone photography and photogrammetry, coupled with U–Pb geochronology, have been used to explore the kinematic history of faulting in onshore exposures along the southern IMFB margin. Dip-slip north–south- to NNE–SSW-striking Devonian growth faults are recognized that have undergone later dextral reactivation during NNW–SSE extension. The U–Pb calcite dating of a sample from the synkinematic calcite veins associated with this later episode shows that the age of fault reactivation is 130.99  ±  4.60 Ma (Hauterivian). The recognition of dextral-oblique Early Cretaceous reactivation of faults related to the underlying and older Orcadian Basin highlights the importance of structural inheritance in controlling basin- to sub-basin-scale architectures and how this influences the kinematics of IMFB rifting

New onshore insights into the role of structural inheritance during Mesozoic opening of the Inner Moray Firth Basin, Scotland

The Inner Moray Firth Basin (IMFB) forms the western arm of the North Sea trilete rift system that initiated mainly during the Late Jurassic–Early Cretaceous with the widespread development of major NE–SW-trending dip-slip growth faults. The IMFB is superimposed over the southern part of the older Devonian Orcadian Basin. The potential influence of older rift-related faults on the kinematics of later Mesozoic basin opening has received little attention, partly owing to the poor resolution of offshore seismic reflection data at depth. New field observations augmented by drone photography and photogrammetry, coupled with U–Pb geochronology, have been used to explore the kinematic history of faulting in onshore exposures along the southern IMFB margin. Dip-slip north–south- to NNE–SSW-striking Devonian growth faults are recognized that have undergone later dextral reactivation during NNW–SSE extension. The U–Pb calcite dating of a sample from the synkinematic calcite veins associated with this later episode shows that the age of fault reactivation is 130.99  ±  4.60 Ma (Hauterivian). The recognition of dextral-oblique Early Cretaceous reactivation of faults related to the underlying and older Orcadian Basin highlights the importance of structural inheritance in controlling basin- to sub-basin-scale architectures and how this influences the kinematics of IMFB rifting

Does rhythm matter in acute heart failure? An insight from the British Society for Heart Failure National Audit

Peer reviewedPublisher PD

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Expert consensus on low-calorie sweeteners:facts, research gaps and suggested actions

A consensus workshop on low-calorie sweeteners (LCS) was held in November 2018 where seventeen experts (the panel) discussed three themes identified as key to the science and policy of LCS: (1) weight management and glucose control; (2) consumption, safety and perception; (3) nutrition policy. The aims were to identify the reliable facts on LCS, suggest research gaps and propose future actions. The panel agreed that the safety of LCS is demonstrated by a substantial body of evidence reviewed by regulatory experts and current levels of consumption, even for high users, are within agreed safety margins. However, better risk communication is needed. More emphasis is required on the role of LCS in helping individuals reduce their sugar and energy intake, which is a public health priority. Based on reviews of clinical evidence to date, the panel concluded that LCS can be beneficial for weight management when they are used to replace sugar in products consumed in the diet (without energy substitution). The available evidence suggests no grounds for concerns about adverse effects of LCS on sweet preference, appetite or glucose control; indeed, LCS may improve diabetic control and dietary compliance. Regarding effects on the human gut microbiota, data are limited and do not provide adequate evidence that LCS affect gut health at doses relevant to human use. The panel identified research priorities, including collation of the totality of evidence on LCS and body weight control, monitoring and modelling of LCS intakes, impacts on sugar reduction and diet quality and developing effective communication strategies to foster informed choice. There is also a need to reconcile policy discrepancies between organisations and reduce regulatory hurdles that impede low-energy product development and reformulation

Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission

IMPORTANCE: Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved. OBJECTIVE: To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022. EXPOSURES: A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes. MAIN OUTCOMES AND MEASURES: Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history. RESULTS: This study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls. CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group

Using UAV-Based Photogrammetry Coupled with In Situ Fieldwork and U-Pb Geochronology to Decipher Multi-Phase Deformation Processes: A Case Study from Sarclet, Inner Moray Firth Basin, UK

Constraining the age of formation and repeated movements along fault arrays in superimposed rift basins helps us to better unravel the kinematic history as well as the role of inherited structures in basin evolution. The Inner Moray Firth Basin (IMFB, western North Sea) overlies rocks of the Caledonian basement, the pre-existing Devonian–Carboniferous Orcadian Basin, and a regionally developed Permo–Triassic North Sea basin system. IMFB rifting occurred mainly in the Upper Jurassic–Lower Cretaceous. The rift basin then experienced further regional tilting, uplift and fault reactivation during the Cenozoic. The Devonian successions exposed onshore along the northwestern coast of IMFB and the southeastern onshore exposures of the Orcadian Basin at Sarclet preserve a variety of fault orientations and structures. Their timing and relationship to the structural development of the wider Orcadian and IMFB are poorly understood. In this study, drone airborne optical images are used to create high-resolution 3D digital outcrops. Analyses of these images are then coupled with detailed field observations and U-Pb geochronology of syn-faulting mineralised veins in order to constrain the orientations and absolute timing of fault populations and decipher the kinematic history of the area. In addition, the findings help to better identify deformation structures associated with earlier basin-forming events. This holistic approach helped identify and characterise multiple deformation events, including the Late Carboniferous inversion of Devonian rifting structures, Permian minor fracturing, Late Jurassic–Early Cretaceous rifting and Cenozoic reactivation and local inversion. We were also able to isolate characteristic structures, fault kinematics, fault rock developments and associated mineralisation types related to these event

How might educational research into children’s ideas about light be of use to teachers?

This paper offers a synthesis of research evidence around teaching light to primary and secondary school pupils, as part of the Institute of Physics (IOP) Promoting and Interpreting Physics Education Research (PIPER) project. Conceptual change literature describes many difficulties young people have with understanding the phenomenon of light, and this knowledge can be useful in the classroom. Pupil teacher dialogue is used to illustrate some of the pedagogical challenges teachers face in this topic. This paper highlights a range of influences on pupils from everyday life and from the classroom, with a view to promoting teacher awareness of conceptual change research evidence