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Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women
Get PDFBACKGROUND: A non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls.METHODS: This was a prospective case-control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression.RESULTS: The top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96-0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86-0.9)).CONCLUSION: A patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted.</p
Implementing a home-based personalised cognitive rehabilitation intervention for people with mild-to-moderate dementia: GREAT into Practice.
Get PDFBackgroundEvidence-based rehabilitative interventions, if widely implemented, could equip people with dementia and their families to manage life with the condition and reduce the need for health and care services. The aim of this translational study, building on evidence from the GREAT randomised controlled trial, was to develop a foundation for implementing the GREAT Cognitive Rehabilitation intervention in community-based services for people with mild-to-moderate dementia.MethodsKey elements of the implementation strategy were identifying and supporting managerial and clinical leadership, conducting collaborative planning and target-setting, training and supporting practitioners, and providing external facilitation. We developed implementation plans with, and trained staff in, 14 organisations. We subsequently worked closely with 11 of these, 10 National Health Service organisations and one private home care provider, to support practitioners to deliver GREAT Cognitive Rehabilitation over a 12-month period. Outcome evaluation examined the perspectives of local steering group members, practitioners and service users, and the reach, effectiveness and cost of the intervention.ResultsImplementation was disrupted by the COVID-19 pandemic, but six organisations completed at least six months of intervention delivery. Forty-one practitioners, mainly occupational therapists, provided the intervention, and 54 people with dementia completed a course of GREAT Cognitive Rehabilitation. Goal attainment by people with dementia exceeded levels of improvement seen in the original trial. People with dementia, carers, practitioners and steering group members all evaluated the intervention positively, and economic analysis indicated that the intervention could be provided at modest cost. However, we identified a range of mainly organisational barriers that impeded implementation and limited the potential for sustainability.ConclusionsGREAT Cognitive Rehabilitation benefits people with dementia, can be delivered effectively at modest cost in routine services, and is viewed positively by people with dementia, family carers and practitioners. To fully realise these benefits and achieve widespread and sustainable implementation, however, requires sufficient resources and a reorientation of service priorities towards preventive and rehabilitative approaches.Trial RegistrationNational Institute for Health Research (NIHR) Central Portfolio Management System, registration number 38994
A stochastic reaction–diffusion modeling investigation of FLASH ultra-high dose rate response in different tissues
Get PDFPurpose: The aim of the study was to propose a theory based on topology andgeometry of diffusion channels in tissue to contribute to the mechanisticunderstanding of normal tissue sparing at ultra-high dose rates (UHDRs) andexplore an interplay between intra- and inter-track radical recombination through a reaction–diffusion mechanism.Methods: We calculate the time evolution of particle track structures using asystem of coupled reaction–diffusion equations on a random network designedfor molecular transport in porous and disordered media. The network isrepresentative of the intra- and inter-cellular diffusion channels in tissues.Spatial cellular heterogeneities over the scale of track spacing are constructedby incorporating random fluctuations in the connectivity between network sites,resembling molecular mass and charge heterogeneities at the cellular level.Results: We demonstrate the occurrence of phase separation among the tracks as the complexity in intra- and inter-cellular structure increases. At the strong limit of structural disorder, tracks evolve individually like isolated islands with negligible inter-track as they propagate like localized waves in space, analogous to the Anderson localization in quantum mechanics. In contrast, at the limit of weak disorder in a homogeneous medium, such as water, the neighboring tracks melt into each other and form a percolated network of non-reactive species. Thus, the spatiotemporal correlation among chemically active domains vanishes as the inter-cellular complexity of the tissue increases from normal tissue structure to fractal-type malignancy.Conclusion: Differential FLASH normal tissue sparing may result from the interplay of the proximity of tracks over the intra- and inter-cellular landscape, a transition in the spatial distribution of chemical reactivity, and molecular crowding. In this context, insensitivities in the radiobiological responses of the tumors to FLASHUHDR are interpreted via a lack of geometrical correlation among isolated tracks. The structural and geometrical complexities of cancerous cells prevent the clustering of tracks over a timescale, in which inter-track chemical reactivities presumably prevail in normal tissues. A series of systematic experiments on radiolysis-induced diffusivity and reactivity in actual normal and cancerou
Exploring ways to increase the use of evidence-based methods in a cluster of schools in Wales
Get PDFDeveloping Excellence in Rugby Union: A Multidisciplinary and Mixed Method Approach to Enhancing the Efficacy of the RFU Talent Development Pathway
Get PDFSeasonal development of a tidal mixing front drives shifts in community structure and diversity of bacterioplankton
Get PDFBacterioplankton underpin biogeochemical cycles and an improved understanding of the patterns and drivers of variability in their distribution is needed to determine their wider functioning and importance. Sharp environmental gradients and dispersal bar-riers associated with ocean fronts are emerging as key determinants of bacterioplank-ton biodiversity patterns. We examined how the development of the Celtic Sea Front (CF), a tidal mixing front on the Northwest European Shelf affects bacterioplankton communities. We performed 16S- rRNA metabarcoding on 60 seawater samples col-lected from three depths (surface, 20 m and seafloor), across two research cruises (May and September 2018), encompassing the intra-annual range of the CF intensity. Communities above the thermocline of stratified frontal waters were clearly differen-tiated and less diverse than those below the thermocline and communities in the well- mixed waters of the Irish Sea. This effect was much more pronounced in September, when the CF was at its peak intensity. The stratified zone likely represents a stressful environment for bacterioplankton due to a combination of high temperatures and low nutrients, which fewer taxa can tolerate. Much of the observed variation was driven by Synechococcus spp. (cyanobacteria), which were more abundant within the strati-fied zone and are known to thrive in warm oligotrophic waters. Synechococcus spp. are key contributors to global primary productivity and carbon cycling and, as such, variability driven by the CF is likely to influence regional biogeochemical processes. However, further studies are required to explicitly link shifts in community structure to function and quantify their wider importance to pelagic ecosystems
Branching coral growth and visual health during bleaching and recovery on the central Great Barrier Reef
Get PDFCoral reefs are under threat from cumulative impacts such as cyclones, crown-of-thorns starfish (COTS) outbreaks and climate-driven coral bleaching events.Branching corals are more severely impacted by these events than other coral morphologies due to their sensitivity to heat stress and weaker skeletons and COTS preferred prey. The central Great Barrier Reef experienced unprecedented back-to-back bleaching events in 2016 and 2017. This study commenced in 2017 at the peak of heat stress and examined the impact of the heatwave on the survival and recovery of corals by assessing the growth, health (based on the visual health index) and physiological parameters (chlorophyll-a, zooxanthellae density, lipid and protein content) of two species, Acropora millepora and Pocillopora acuta (N = 60 colonies for each species). It was conducted across a gradient of turbidity at three reefs, Pandora, Orpheus and Rib, that experienced in April 2017, degree heating weeks (DHW) of 9, 8 and 7, respectively. Orpheus experienced the worst bleaching, based on visual health score, followed by Riband Pandora. Rib experienced the greatest mortality (78% by Nov 2017); however, this was attributed to the presence of actively feeding crown-of-thorns starfish. Growth rates of A. millepora were almost twice the rate of P. acuta. Bothspecies showed significant seasonal variation with growth of A. millepora and P. acuta 35–40% and 23–33% significantly greater in the summer, respectively. Differences in growth rates were best explained by indicators of energy acquisition. For example, the most important predictor variable in determining higher growth rates and visual health score in A. millepora was chlorophyll-a content. For P. acuta, visual health score was the best predictor variable for higher growth rates. This study highlights the important role that chlorophyll-a and associated symbionts play in growth and survival in these corals during and after a heat stress event
Cognitive training and remediation interventions for substance use disorders:a Delphi consensus study
Get PDFAIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review.MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery.FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities.CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.</p
Self-Talk: An Interdisciplinary Review and Transdisciplinary Model
Get PDFThe present work synthesises the self-talk literature and constructs a transdisciplinary self-talk model to guide future research across all academic disciplines that engage with self-talk. A comprehensive research review was conducted, including 559 self-talk articles published between 1978 and 2020. These articles were divided into 6 research categories: (a) inner dialogue, (b) mixed spontaneous and goal-directed organic self-talk, (c) goal-directed self-talk, (d) spontaneous self-talk, (e) educational self-talk interventions, and (f) strategic self-talk interventions. Following this, critical details were extracted from a subsample of 100 articles to create an interdisciplinary synthesis of the self-talk literature. Based on the synthesis, a self-talk model was created that places spontaneous and goal-directed organic self-talk as well as educational and strategic self-talk interventions in relation to variables within their nomological network, including external factors (e.g. task difficulty), descriptive states and traits (e.g. emotions), behaviour and performance, metacognition, and psychological skills (e.g. concentration)
Sustainable Land Management and Climate Change Adaptation for Small-Scale Land Users in Sub-Saharan Africa
Get PDFLand is both a source and a sink of carbon dioxide (CO2), the chief greenhouse gas. Through sustainable land management (SLM), it can capture extra CO2 and store it as carbon in vegetation and soil. SLM can also reduce CO2 emissions from the land. Thus, SLM is viewed as the key land-based solution for climate change mitigation. Yet, SLM also provides effective climate change (CC) adaptation practices—such as agroforestry, mulching and water harvesting—which confer resilience, and simultaneously help secure production. This is especially valuable for land users in sub-Saharan Africa (SSA) who depend on rainfed agriculture. They are amongst the poorest on Earth and the most vulnerable to CC impacts, despite their minimal carbon footprint. The World Overview of Conservation Approaches and Technologies (WOCAT) manages the Global SLM Database: this holds a rich and ever-growing collection of SLM practices. Analysis of the database for rainfed SSA sheds light on which SLM technologies are effective in CC adaptation, and how well they cope with changing rainfall and temperature. Both “mechanisms” and “attributes” are explored, yielding new insights. This perspective paper showcases current developments in the field, and summarizes future directions for SLM as a CC adaptation solution for land users in SSA