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Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.

Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.

The analytical study of confinement in lattice gauge theories (LGTs) remains a difficult task to this day. Taking a geometric perspective on confinement, we develop a real-space renormalization group (RG) formalism for $\mathbb{Z}_2$ LGTs using percolation probability as a confinement order parameter. The RG flow we analyze is constituted by both the percolation probability and the coupling parameters. We consider a classical $\mathbb{Z}_2$ LGT in two dimensions, with matter and thermal fluctuations, and analytically derive the confinement phase diagram. We find good agreement with numerical and exact benchmark results and confirm that a finite matter density enforces confinement at $T<\infty$ in the model we consider. Our RG scheme enables future analytical studies of $\mathbb{Z}_2$ LGTs with matter and quantum fluctuations and beyond., Comment: 7+6 pages, 8+1 figures

Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and bidirectionally with GERD. Gene-based analyses reveal a gene-level genetic overlap between T2D and GI disorders and identify several shared genes reaching genome-wide significance. Pathway-based study implicates leptin (T2D – IBD), thyroid, interferon, and notch signalling (T2D – IBS), abnormal circulating calcium (T2D – PUD), cardiovascular, viral, proinflammatory and (auto)immune-mediated mechanisms in T2D and GI disorders. These findings support a risk-increasing genetic overlap between T2D and GI disorders (except IBD), implicate shared biological pathways with putative causality for certain T2D – GI pairs, and identify targets for further investigation.

Plant communities are being exposed to changing environmental conditions all around the globe, leading to alterations in plant diversity, community composition, and ecosystem functioning. For herbaceous understorey communities in temperate forests, responses to global change are postulated to be complex, due to the presence of a tree layer that modulates understorey responses to external pressures such as climate change and changes in atmospheric nitrogen deposition rates. Multiple investigative approaches have been put forward as tools to detect, quantify and predict understorey responses to these global-change drivers, including, among others, distributed resurvey studies and manipulative experiments. These investigative approaches are generally designed and reported upon in isolation, while integration across investigative approaches is rarely considered. In this study, we integrate three investigative approaches (two complementary resurvey approaches and one experimental approach) to investigate how climate warming and changes in nitrogen deposition affect the functional composition of the understorey and how functional responses in the understorey are modulated by canopy disturbance, that is, changes in overstorey canopy openness over time. Our resurvey data reveal that most changes in understorey functional characteristics represent responses to changes in canopy openness with shifts in macroclimate temperature and aerial nitrogen deposition playing secondary roles. Contrary to expectations, we found little evidence that these drivers interact. In addition, experimental findings deviated from the observational findings, suggesting that the forces driving understorey change at the regional scale differ from those driving change at the forest floor (i.e., the experimental treatments). Our study demonstrates that different approaches need to be integrated to acquire a full picture of how understorey communities respond to global change.

Background: Complex disorders, such as Alzheimer’s disease (AD), result from the combined influence of multiple biological and environmental factors. The integration of high-throughput data from multiple omics platforms can provide system overviews, improving our understanding of complex biological processes underlying human disease. In this study, integrated data from four omics platforms were used to characterise biological signatures of AD. Method: The study cohort consists of 455 participants (Control:148, Cases:307) from the Religious Orders Study and Memory and Aging Project (ROSMAP). Genotype (SNP), methylation (CpG), RNA and proteomics data were collected, quality-controlled and pre-processed (SNP = 130; CpG = 83; RNA = 91; Proteomics = 119). Using a diagnosis of Mild Cognitive Impairment (MCI)/AD combined as the target phenotype, we first used Partial Least Squares Regression as an unsupervised classification framework to assess the prediction capabilities for each omics dataset individually. We then used a variation of the sparse generalized canonical correlation analysis (sGCCA) to assess predictions of the combined datasets and identify multi-omics signatures characterising each group of participants. Results: Analysing datasets individually we found methylation data provided the best predictions with an accuracy of 0.63 (95%CI = [0.54–0.71]), followed by RNA, 0.61 (95%CI = [0.52–0.69]), SNP, 0.59 (95%CI = [0.51–0.68]) and proteomics, 0.58 (95%CI = [0.51–0.67]). After integration of the four datasets, predictions were dramatically improved with a resulting accuracy of 0.95 (95% CI = [0.89–0.98]). Conclusion: The integration of data from multiple platforms is a powerful approach to explore biological systems and better characterise the biological signatures of AD. The results suggest that integrative methods can identify biomarker panels with improved predictive performance compared to individual platforms alone. Further validation in independent cohorts

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.

There can be little doubt of the canonical drone aesthetic: a flattened aeriality that moves with an inhuman smoothness, drifting and pitching to capture an uncanny vantage. But with the unfolding, contested landscape of drone development and proliferating drone use, how is this disruptive technology changing our understanding of war, culture, and ecology? This edited collection offers a pluralized understanding of drones by bringing together twelve essays from interdisciplinary scholars working on drone pasts and drone futures, encompassing fields such as cultural anthropology, critical war studies, disability studies, international relations, media studies, and cultural studies. It examines the intersection between drones and aesthetics in terms of visual culture and the arts; the body and its relationship to the material environment; the mechanic capacities for sensing and sense-making; and in terms of politics and what makes politics possible. To more fully account for the unique politics of drone perception, it also features three visual essays by multimedia artists whose aesthetic practices have shaped the field of drone scholarship. Offering new ideas and arguments about the technology, logics, and systems with which drones are intertwined, this collection scrutinises how the aesthetics of drones are fundamental to its ethics; how drone aesthetics are impacting the way we relate to one another and to the human and more-than-human worlds; and how drones are altering our relationships to life and death., https://www.librarystack.org/drone-aesthetics-war-culture-ecology/?ref=unknown

Globally pervasive increases in atmospheric CO2 and nitrogen (N) deposition could have substantial effects on plant communities, either directly or mediated by their interactions with soil nutrient limitation. While the direct consequences of N enrichment on plant communities are well documented, potential interactions with rising CO2 and globally widespread phosphorus (P) limitation remain poorly understood. We investigated the consequences of simultaneous elevated CO2 (eCO2) and N and P additions on grassland biodiversity, community and functional composition in P‐limited grasslands. We exposed soil‐turf monoliths from limestone and acidic grasslands that have received >25 years of N additions (3.5 and 14 g m−2 year−1) and 11 (limestone) or 25 (acidic) years of P additions (3.5 g m−2 year−1) to eCO2 (600 ppm) for 3 years. Across both grasslands, eCO2, N and P additions significantly changed community composition. Limestone communities were more responsive to eCO2 and saw significant functional shifts resulting from eCO2–nutrient interactions. Here, legume cover tripled in response to combined eCO2 and P additions, and combined eCO2 and N treatments shifted functional dominance from grasses to sedges. We suggest that eCO2 may disproportionately benefit P acquisition by sedges by subsidising the carbon cost of locally intense root exudation at the expense of co‐occurring grasses. In contrast, the functional composition of the acidic grassland was insensitive to eCO2 and its interactions with nutrient additions. Greater diversity of P‐acquisition strategies in the limestone grassland, combined with a more functionally even and diverse community, may contribute to the stronger responses compared to the acidic grassland. Our work suggests we may see large changes in the composition and biodiversity of P‐limited grasslands in response to eCO2 and its interactions with nutrient loading, particularly where these contain a high diversity of P‐acquisition strategies or deve

Plant communities are being exposed to changing environmental conditions all around the globe, leading to alterations in plant diversity, community composition, and ecosystem functioning. For herbaceous understorey communities in temperate forests, responses to global change are postulated to be complex, due to the presence of a tree layer that modulates understorey responses to external pressures such as climate change and changes in atmospheric nitrogen deposition rates. Multiple investigative approaches have been put forward as tools to detect, quantify and predict understorey responses to these global-change drivers, including, among others, distributed resurvey studies and manipulative experiments. These investigative approaches are generally designed and reported upon in isolation, while integration across investigative approaches is rarely considered. In this study, we integrate three investigative approaches (two complementary resurvey approaches and one experimental approach) to investigate how climate warming and changes in nitrogen deposition affect the functional composition of the understorey and how functional responses in the understorey are modulated by canopy disturbance, that is, changes in overstorey canopy openness over time. Our resurvey data reveal that most changes in understorey functional characteristics represent responses to changes in canopy openness with shifts in macroclimate temperature and aerial nitrogen deposition playing secondary roles. Contrary to expectations, we found little evidence that these drivers interact. In addition, experimental findings deviated from the observational findings, suggesting that the forces driving understorey change at the regional scale differ from those driving change at the forest floor (i.e., the experimental treatments). Our study demonstrates that different approaches need to be integrated to acquire a full picture of how understorey communities respond to global change.

Background:Despite evidence that formalized trauma systems enhance patient functional outcomes and decrease mortality rates, there remains a lack of such systems globally. Critical to trauma systems are the equipment, materials, and supplies needed to support care, which vary in availability regionally. The purpose of the present study was to identify essential resources for musculoskeletal trauma care across diverse resource settings worldwide.Methods:The modified Delphi method was utilized, with 3 rounds of electronic surveys. Respondents consisted of 1 surgeon with expertise in musculoskeletal trauma per country. Participants were identified with use of the AO Trauma, AO Alliance, Orthopaedic Trauma Association, and European Society for Trauma and Emergency Surgery networks. Respondents rated resources on a Likert scale from 1 (most important) to 9 (least important). The "most essential" resources were classified as those rated ≤2 by ≥75% of the sampled group.Results:One hundred and three of 111 invited surgeons completed the first survey and were included throughout the subsequent rounds (representing a 93% response rate). Most participants were fellowship-Trained (78%) trauma and orthopaedic surgeons (90%) practicing in an academic setting (62%), and 46% had >20 years of experience. Respondents represented low-income and lower-middle-income countries (LMICs; 35%), upper-middle income countries (UMICs; 30%), and high-income countries (HICs; 35%). The initial survey identified 308 unique resources for pre-hospital, in-hospital, and post-hospital phases of care, of which 71 resources achieved consensus as the most essential. There was a significant difference (p < 0.0167) in ratings between income groups for 16 resources, all of which were related to general trauma care rather than musculoskeletal injury management.Conclusions:There was agreement on a core list of essential muscu

Globally pervasive increases in atmospheric CO2 and nitrogen (N) deposition could have substantial effects on plant communities, either directly or mediated by their interactions with soil nutrient limitation. While the direct consequences of N enrichment on plant communities are well documented, potential interactions with rising CO2 and globally widespread phosphorus (P) limitation remain poorly understood. We investigated the consequences of simultaneous elevated CO2 (eCO2) and N and P additions on grassland biodiversity, community and functional composition in P-limited grasslands. We exposed soil-turf monoliths from limestone and acidic grasslands that have received >25 years of N additions (3.5 and 14 g m−2 year−1) and 11 (limestone) or 25 (acidic) years of P additions (3.5 g m−2 year−1) to eCO2 (600 ppm) for 3 years. Across both grasslands, eCO2, N and P additions significantly changed community composition. Limestone communities were more responsive to eCO2 and saw significant functional shifts resulting from eCO2–nutrient interactions. Here, legume cover tripled in response to combined eCO2 and P additions, and combined eCO2 and N treatments shifted functional dominance from grasses to sedges. We suggest that eCO2 may disproportionately benefit P acquisition by sedges by subsidising the carbon cost of locally intense root exudation at the expense of co-occurring grasses. In contrast, the functional composition of the acidic grassland was insensitive to eCO2 and its interactions with nutrient additions. Greater diversity of P-acquisition strategies in the limestone grassland, combined with a more functionally even and diverse community, may contribute to the stronger responses compared to the acidic grassland. Our work suggests we may see large changes in the composition and biodiversity of P-limited grasslands in response to eCO2 and its interactions with nutrient loading, particularly where these contain a high diversity of P-acquisition strategies or deve

Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.

Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.

Background/Objective: (1) Examine the role of exercise intensity on mental health symptoms in a community-based sample of older adults. (2) Explore the moderating role of genetic variation in brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) on the effects of exercise on mental health symptoms. Method: This study is a secondary analysis of a three-arm randomized controlled trial, comparing the effects of 6 months of high-intensity aerobic training vs. moderate-intensity aerobic training vs. a no-contact control group on mental health symptoms assessed using the Depression, Anxiety, and Stress Scale (DASS). The BDNF Val66Met polymorphism and APOE 4 carrier status were explored as genetic moderators of exercise effects on mental health symptoms. Results: The exercise intervention did not influence mental health symptoms. The BDNF Val66Met polymorphism did not moderate intervention effects on mental health symptoms. APOE 4 carrier status moderated the effect of intervention group on perceived stress over 6 months, such that APOE 4 carriers, but not non-carriers, in the high-intensity aerobic training group showed a decline in perceived stress over 6 months. Conclusions: APOE 4 carrier status may modify the benefits of high-intensity exercise on perceived stress such that APOE 4 carriers show a greater decline in stress as a result of exercise relative to non-APOE 4 carriers.

Elite sports contexts are highly pressurised and frequently enforce a win-at-all-costs approach. This narrow focus on performance outcomes can potentially contribute in negative ways to the mental health of those within these environments. In this Current Opinion paper, we propose a model that outlines how key elements contributing to psychologically safe or unsafe environments may contribute to better or worse mental health outcomes, respectively. In an environment in which individuals feel safe to show their authentic selves rather than 'wear a mask', different experiences of mental health are likely to be normalised, help-seeking behaviour increased, and thus, mental health outcomes enhanced. We outline how sports teams and organisations can contribute to this through the creation of appropriate policies and procedures, in addition to leaders modelling and reinforcing positive cultural norms. It is intended that the theoretical model can inform stakeholders in elite sport as well as future research directions.

There is growing concern over climate models that project significant changes in the oceans, with consequences on marine biodiversity and human well-being. However, marine and coastal ecosystems respond differently to climate change-related stressors depending on the ecosystem, species composition and interactions, geomorphologic settings, and spatial distribution, but also on the presence of local stressors interacting cumulatively with climate change-related pressures. Our paper provides a comprehensive review of the current literature about the effects of climate-related pressures on marine and coastal ecosystems and how local stressors affect their resilience. Our work focuses on key marine and coastal ecosystems from three ecoregions: the Caribbean Sea (coral reefs, mangrove forests, seagrass beds), the Mediterranean Sea (the coral Cladocora caespitosa, maërl beds and seagrass beds) and the North-East Atlantic, which include kelp forests, maërl beds, salt marshes and seagrass beds. This review highlights the need for a more comprehensive, multi-species, and multi-stressors approach to predict better changes at the ecosystem and seascape levels of marine and coastal ecosystems. Nevertheless, there is enough evidence to argue that addressing locally key manageable stressors common to multiple ecosystems, such as nutrient enrichment, coastal development, hydrologic disturbances, anchoring or sedimentation, will reduce the identified adverse effects of climate change. This knowledge is critical for practical conservation actions and coastal and marine spatial management at the ecoregion scale and beyond

There is growing concern over climate models that project significant changes in the oceans, with consequences on marine biodiversity and human well-being. However, marine and coastal ecosystems respond differently to climate change-related stressors depending on the ecosystem, species composition and interactions, geomorphologic settings, and spatial distribution, but also on the presence of local stressors interacting cumulatively with climate change-related pressures. Our paper provides a comprehensive review of the current literature about the effects of climate-related pressures on marine and coastal ecosystems and how local stressors affect their resilience. Our work focuses on key marine and coastal ecosystems from three ecoregions: the Caribbean Sea (coral reefs, mangrove forests, seagrass beds), the Mediterranean Sea (the coral Cladocora caespitosa, maërl beds and seagrass beds) and the North-East Atlantic, which include kelp forests, maërl beds, salt marshes and seagrass beds. This review highlights the need for a more comprehensive, multi-species, and multi-stressors approach to predict better changes at the ecosystem and seascape levels of marine and coastal ecosystems. Nevertheless, there is enough evidence to argue that addressing locally key manageable stressors common to multiple ecosystems, such as nutrient enrichment, coastal development, hydrologic disturbances, anchoring or sedimentation, will reduce the identified adverse effects of climate change. This knowledge is critical for practical conservation actions and coastal and marine spatial management at the ecoregion scale and beyond.

Close binary systems present challenges to planet formation. As binary separations decrease, so too do the occurrence rates of protoplanetary disks in young systems and planets in mature systems. For systems that do retain disks, their disk masses and sizes are altered by the presence of the binary companion. Through the study of protoplanetary disks in binary systems with known orbital parameters, we seek to determine the properties that promote disk retention and, therefore, planet formation. In this work, we characterize the young binary-disk system, FO Tau. We determine the first full orbital solution for the system, finding masses of $0.35^{+0.06}_{-0.05}\ M_\odot$ and $0.34\pm0.05\ M_\odot$ for the stellar components, a semi-major axis of $22(^{+2}_{-1})$ AU, and an eccentricity of $0.21(^{+0.04}_{-0.03})$. With long-baseline ALMA interferometry, we detect 1.3mm continuum and $^{12}{\mathrm{CO}} \ (J=2-1)$ line emission toward each of the binary components; no circumbinary emission is detected. The protoplanetary disks are compact, consistent with being truncated by the binary orbit. The dust disks are unresolved in the image plane and the more extended gas disks are only marginally resolved. Fitting the continuum and CO visibilities, we determine the inclination of each disk, finding evidence for alignment of the disk and binary orbital planes. This study is the first of its kind linking the properties of circumstellar protoplanetary disks to a precisely known binary orbit. In the case of FO Tau, we find a dynamically placid environment (coplanar, low eccentricity), which may foster its potential for planet formation., Comment: AJ accepted, 29 pages, 14 figures

BACKGROUND: Despite evidence that formalized trauma systems enhance patient functional outcomes and decrease mortality rates, there remains a lack of such systems globally. Critical to trauma systems are the equipment, materials, and supplies needed to support care, which vary in availability regionally. The purpose of the present study was to identify essential resources for musculoskeletal trauma care across diverse resource settings worldwide. METHODS: The modified Delphi method was utilized, with 3 rounds of electronic surveys. Respondents consisted of 1 surgeon with expertise in musculoskeletal trauma per country. Participants were identified with use of the AO Trauma, AO Alliance, Orthopaedic Trauma Association, and European Society for Trauma and Emergency Surgery networks. Respondents rated resources on a Likert scale from 1 (most important) to 9 (least important). The "most essential" resources were classified as those rated ≤2 by ≥75% of the sampled group. RESULTS: One hundred and three of 111 invited surgeons completed the first survey and were included throughout the subsequent rounds (representing a 93% response rate). Most participants were fellowship-trained (78%) trauma and orthopaedic surgeons (90%) practicing in an academic setting (62%), and 46% had >20 years of experience. Respondents represented low-income and lower-middle-income countries (LMICs; 35%), upper-middle income countries (UMICs; 30%), and high-income countries (HICs; 35%). The initial survey identified 308 unique resources for pre-hospital, in-hospital, and post-hospital phases of care, of which 71 resources achieved consensus as the most essential. There was a significant difference (p < 0.0167) in ratings between income groups for 16 resources, all of which were related to general trauma care rather than musculoskeletal injury management. CONCLUSIONS: There was agreement on a core list of essential musculoskeletal trauma care resources by respondents from LMICs, UMICs, and HICs. Al

Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers., Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers.

Introduction Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient sensing via transporters and G protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacological preparations for the treatment of T2DM. However, physiologically stimulated GLP-1 secretion through the diet might be a preventive or synergistic method for improving glucose metabolism in individuals who are OW, or have impaired glucose tolerance (IGT) or T2DM. Rationale This narrative review focuses on fasting and postprandial GLP-1 secretion in individuals with different metabolic conditions and degrees of glucose intolerance. Further, the influence of relevant diet-related factors (e.g., specific diets, meal composition and size, phytochemical content, and gut microbiome) that could affect fasting and postprandial GLP-1 secretion are discussed. Results Some studies showed a diminished glucose- or meal-stimulated GLP-1 response in participants with T2DM, IGT, or OW compared to those with NGT, whereas other studies have reported an elevated or unchanged GLP-1 response in T2DM or IGT. Meal composition, especially the relationship between macronutrients and interventions targeting the microbiome can impact postprandial GLP-1 secretion, although it is not clear which macronutrients are strong stimulants of GLP-1. Moreover, glucose tolerance, antidiabetic treatment, grade of overweight/obesity, and sex were important factors influencing GLP-1 secretion. Conclusion The results presented in this review highlig, INTRODUCTION: Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient sensing via transporters and G protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacological preparations for the treatment of T2DM. However, physiologically stimulated GLP-1 secretion through the diet might be a preventive or synergistic method for improving glucose metabolism in individuals who are OW, or have impaired glucose tolerance (IGT) or T2DM.RATIONALE: This narrative review focuses on fasting and postprandial GLP-1 secretion in individuals with different metabolic conditions and degrees of glucose intolerance. Further, the influence of relevant diet-related factors (e.g., specific diets, meal composition and size, phytochemical content, and gut microbiome) that could affect fasting and postprandial GLP-1 secretion are discussed.RESULTS: Some studies showed a diminished glucose- or meal-stimulated GLP-1 response in participants with T2DM, IGT, or OW compared to those with NGT, whereas other studies have reported an elevated or unchanged GLP-1 response in T2DM or IGT. Meal composition, especially the relationship between macronutrients and interventions targeting the microbiome can impact postprandial GLP-1 secretion, although it is not clear which macronutrients are strong stimulants of GLP-1. Moreover, glucose tolerance, antidiabetic treatment, grade of overweight/obesity, and sex were important factors influencing GLP-1 secretion.CONCLUSION: The results presented in this review highlight the potential o

The growing interest in regenerative medicine has opened new avenues for novel cell therapies using stem cells. Bone marrow aspirate (BMA) is an important source of stromal mesenchymal stem cells (MSCs). Conventional MSC harvesting from BMA relies on archaic centrifugation methods, often leading to poor yield due to osmotic stress, high centrifugation force, convoluted workflow, and long experimental time (∼2–3 hours). To address these issues, we have developed a scalable microfluidic technology based on deterministic lateral displacement (DLD) for MSC isolation. This passive, label-free cell sorting method capitalizes on the morphological differences between MSCs and blood cells (platelets and RBCs) for effective separation using an inverted L-shaped pillar array. To improve throughput, we developed a novel multi-chip DLD system that can process 2.5 mL of raw BMA in 20 ± 5 minutes, achieving a 2-fold increase in MSC recovery compared to centrifugation methods. Taken together, we envision that the developed DLD platform will enable fast and efficient isolation of MSCs from BMA for effective downstream cell therapy in clinical settings., National Research Foundation Singapore

Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers., Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers.

Introduction Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient sensing via transporters and G protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacological preparations for the treatment of T2DM. However, physiologically stimulated GLP-1 secretion through the diet might be a preventive or synergistic method for improving glucose metabolism in individuals who are OW, or have impaired glucose tolerance (IGT) or T2DM. Rationale This narrative review focuses on fasting and postprandial GLP-1 secretion in individuals with different metabolic conditions and degrees of glucose intolerance. Further, the influence of relevant diet-related factors (e.g., specific diets, meal composition and size, phytochemical content, and gut microbiome) that could affect fasting and postprandial GLP-1 secretion are discussed. Results Some studies showed a diminished glucose- or meal-stimulated GLP-1 response in participants with T2DM, IGT, or OW compared to those with NGT, whereas other studies have reported an elevated or unchanged GLP-1 response in T2DM or IGT. Meal composition, especially the relationship between macronutrients and interventions targeting the microbiome can impact postprandial GLP-1 secretion, although it is not clear which macronutrients are strong stimulants of GLP-1. Moreover, glucose tolerance, antidiabetic treatment, grade of overweight/obesity, and sex were important factors influencing GLP-1 secretion. Conclusion The results presented in this review highlig, INTRODUCTION: Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide and central mediator of glucose metabolism, is secreted by L cells in the intestine in response to food intake. Postprandial secretion of GLP-1 is triggered by nutrient sensing via transporters and G protein-coupled receptors (GPCRs). GLP-1 secretion may be lower in adults with obesity (OW) or type 2 diabetes mellitus (T2DM) than in those with normal glucose tolerance (NGT), but these findings are inconsistent. Because of the actions of GLP-1 on stimulating insulin secretion and promoting weight loss, GLP-1 and its analogs are used in pharmacological preparations for the treatment of T2DM. However, physiologically stimulated GLP-1 secretion through the diet might be a preventive or synergistic method for improving glucose metabolism in individuals who are OW, or have impaired glucose tolerance (IGT) or T2DM.RATIONALE: This narrative review focuses on fasting and postprandial GLP-1 secretion in individuals with different metabolic conditions and degrees of glucose intolerance. Further, the influence of relevant diet-related factors (e.g., specific diets, meal composition and size, phytochemical content, and gut microbiome) that could affect fasting and postprandial GLP-1 secretion are discussed.RESULTS: Some studies showed a diminished glucose- or meal-stimulated GLP-1 response in participants with T2DM, IGT, or OW compared to those with NGT, whereas other studies have reported an elevated or unchanged GLP-1 response in T2DM or IGT. Meal composition, especially the relationship between macronutrients and interventions targeting the microbiome can impact postprandial GLP-1 secretion, although it is not clear which macronutrients are strong stimulants of GLP-1. Moreover, glucose tolerance, antidiabetic treatment, grade of overweight/obesity, and sex were important factors influencing GLP-1 secretion.CONCLUSION: The results presented in this review highlight the potential o

Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics. Commonly measured soil metrics were analysed in five soil increments for 0–1 metre (n = 4550). Less commonly measured soil metrics which were assumed to change across the soil profile were measured on a subset of samples only (n = 3762). Additionally, we developed a simple method for soil organic matter fractionation using density fractionation which is part of the less common metrics. Finally, soil metrics which may impact SOC dynamics, but with less confidence as to their importance across the soil profile were only measured on topsoil (~5–15 cm = mineral soil) and subsoil (below 50 cm) samples (n = 2567).

•1. To predict how biodiversity will respond to global change, it is crucial to understand the relative roles of abiotic drivers and biotic interactions in driving associations between the biodiversity of disparate taxa. It is particularly challenging to understand diversity–diversity links across domains and habitats, because data are rarely available for multiple above- and below-ground taxa across multiple sites. •2. Here, we analyse data from a unique biodiversity data set gathered across a variety of oceanic temperate terrestrial habitats in Wales, comprising 300 sites with co-located soil microbial, plant, bird and pollinator surveys along with climate and soil physicochemical information. Soil groups are analysed using metabarcoding of the 16S, ITS1 and 18S DNA regions, allowing in-depth characterisation of microbial and soil animal biodiversity. •3. We explore biodiversity relationships along three aspects of community composition: First, we assess correlation between the alpha diversity of different groups. Second, we assess whether biotic turnover between sites is correlated across different groups. Finally, we investigate the co-occurrence of individual taxa across sites. In each analysis, we assess the contribution of linear or nonlinear environmental effects. •4. We find that a positive correlation between alpha diversity of plants, soil bacteria, soil fungi, soil heterotrophic protists, bees and butterflies is in fact driven by complex nonlinear responses to abiotic drivers. In contrast, environmental variation did not account for positive associations between the diversity of plants and both birds and AM fungi, suggesting a role for biotic interactions. •5. Both the diversity and taxon-level associations between the differing soil groups remained even after accounting for nonlinear environmental gradients. Above-ground, spatial factors played larger roles in driving biotic communities, while linear environmental gradients were sufficient to explain ma

The Antiproton Decelerator (AD) at CERN provides antiproton bunches with a kinetic energy of 5.3 MeV. The Extra-Low ENergy Antiproton ring at CERN, commissioned at the AD in 2018, now supplies a bunch of electron-cooled antiprotons at a fixed energy of 100 keV. The MUSASHI antiproton trap was upgraded by replacing the radio-frequency quadrupole decelerator with a pulsed drift tube to re-accelerate antiprotons and optimize the injection energy into the degrader foils. By increasing the beam energy to 119 keV, a cooled antiproton accumulation efficiency of (26 +- 6)% was achieved., Comment: 22 pages, 8 figures

Lattice gauge theories (LGTs) were introduced in 1974 by Wilson to study quark confinement. These models have been shown to exhibit (de-)confined phases, yet it remains challenging to define experimentally accessible order parameters. Here we propose percolation-inspired order parameters (POPs) to probe confinement of dynamical matter in $\mathbb{Z}_2$ LGTs using electric field basis snapshots accessible to quantum simulators. We apply the POPs to study a classical $\mathbb{Z}_2$ LGT and find a confining phase up to temperature $T=\infty$ in 2D (critical $T_c$, i.e. finite-$T$ phase transition, in 3D) for any non-zero density of $\mathbb{Z}_2$ charges. Further, using quantum Monte Carlo we demonstrate that the POPs reproduce the square lattice Fradkin-Shenker phase diagram at $T=0$ and explore the phase diagram at $T>0$. The correlation length exponent coincides with the one of the 3D Ising universality class and we determine the POP critical exponent characterizing percolation. Our proposed POPs provide a geometric perspective of confinement and are directly accessible to snapshots obtained in quantum simulators, making them suitable as a probe for quantum spin liquids., Comment: 5+9 pages, 4+6 figures

We propose and analyze a family of approximately-symmetric neural networks for quantum spin liquid problems. These tailored architectures are parameter-efficient, scalable, and significantly out-perform existing symmetry-unaware neural network architectures. Utilizing the mixed-field toric code model, we demonstrate that our approach is competitive with the state-of-the-art tensor network and quantum Monte Carlo methods. Moreover, at the largest system sizes (N=480), our method allows us to explore Hamiltonians with sign problems beyond the reach of both quantum Monte Carlo and finite-size matrix-product states. The network comprises an exactly symmetric block following a non-symmetric block, which we argue learns a transformation of the ground state analogous to quasiadiabatic continuation. Our work paves the way toward investigating quantum spin liquid problems within interpretable neural network architectures, Comment: 5+10 pages

Since the advent of Deepfakes in digital media, the development of robust and reliable detection mechanism is urgently called for. In this study, we explore a novel approach to Deepfake detection by utilizing electroencephalography (EEG) measured from the neural processing of a human participant who viewed and categorized Deepfake stimuli from the FaceForensics++ datset. These measurements serve as input features to a binary support vector classifier, trained to discriminate between real and manipulated facial images. We examine whether EEG data can inform Deepfake detection and also if it can provide a generalized representation capable of identifying Deepfakes beyond the training domain. Our preliminary results indicate that human neural processing signals can be successfully integrated into Deepfake detection frameworks and hint at the potential for a generalized neural representation of artifacts in computer generated faces. Moreover, our study provides next steps towards the understanding of how digital realism is embedded in the human cognitive system, possibly enabling the development of more realistic digital avatars in the future.

The Kunming-Montreal Global Biodiversity Framework, launched during the United Nations Biodiversity Conference in December 2022, encourages governments, companies, and investors to publish data on their nature-related risks, dependencies, and impacts. These disclosures are intended to drive businesses to recognise, manage and mitigate their reliance on ecosystem goods and services. However, there is a “biodiversity blind spot” that is evident for most organisations and business schools. Business education rarely addresses the root causes of biodiversity loss, such as the unsustainable exploitation of natural resources. As the dominant positioning of Education for Sustainable Development Goals (ESDG) presents biodiversity in anthropocentric instrumental terms inadequate for addressing ecosystem decline, we posit that a more progressive and transformative ecocentric education through ecopedagogy and ecoliteracy is needed. Both approaches include the development of critical thinking about degrowth, circular economy, and conventional stakeholder theory to include non-human stakeholders. Using comparative case studies from Northumbria University, the University of Hong Kong, and Amsterdam University of Applied Sciences, we illustrate how business education can be transformed to address biodiversity loss, providing theoretical guidance and practical recommendations to academic practitioners and future business leaders.

ITER envisages the use of two heating neutral beam injectors plus an optional one as part of the auxiliary heating and current drive system, to reach the desired performances during its various phases of operation. The 16.5 MW expected neutral beam power per injector is several notches higher than worldwide existing facilities. In order to enable such development, a Neutral Beam Test Facility (NBTF) was established at Consorzio RFX, exploiting the synergy of two test beds, called SPIDER and MITICA. SPIDER is dedicated developing and characterizing large efficient negative ion sources at relevant parameters in ITER-like conditions: source and accelerator located in the same vacuum where the beam propagates, immunity to electromagnetic interferences of multiple radio-frequency (RF) antennas, avoidance of RF-induced discharges on the outside of the source. Three years of experiments on SPIDER have addressed to the necessary design modifications to enable full performances. The source is presently under a long shut-down phase to incorporate learnings from the experimental campaign, in particular events/issues occurred during operation, which led to the identification of improvement opportunities/necessities (e.g. RF discharges, local burns, water leaks, other damages, configuration/design upgrades to maximize chances/margin to quest target parameters). Parallelly, developments on MITICA, the full-scale prototype of the ITER Neutral Beam Injector (NBI) featuring a 1 MV accelerator and ion neutralization, are underway including manufacturing of the beam source, accelerator and the beam line components, while power supplies and auxiliary plants, already installed, are under final testing and commissioning. Integration, commissioning and tests of the 1 MV power supplies are essential for this first-of-kind system, unparalleled both in research and industry field. 1.2 MV dc insulating tests of high voltage components were successfully completed. The integrated test to confir

Objective: To provide qualitative empirical data on parental expectations of diagnostic prenatal genomic sequencing and the value of the results to families. Methods: We interviewed 15 families-mothers and/or fathers-who had had prenatal genomic sequencing about their expectations and their respective evaluations of the benefits of genomic sequencing. Results: Families' hopes for genetic sequencing clustered around three themes: hoping to identify the cause of the fetal anomaly in a terminated pregnancy; hopes for guidance as to the likely outcome of current pregnancy; and hopes for information to support future family planning. In addition, hopes were discussed in terms of the potential for results to be beneficial in acquiring greater knowledge, while at the same time recognizing that new knowledge may raise more questions. Assessment of the value of sequencing largely mirrored these expectations when positive results seen. Negative results can also be seen as valuable in ruling out a genetic cause and in providing certainty that families had done everything that they could to know about the cause of fetal demise. Conclusion: It would appear that with guidance from genetic counsellors, families were largely able to navigate the many uncertainties of prenatal genomic sequencing and thus see themselves as benefitting from sequencing. However, support structures are essential to guide them through their expectations and interpretations of results to minimize possible harms. Engaging in the process of genomic sequencing was seen as beneficial in of itself to families who would otherwise be left without any options to seek diagnostic answers.

Distal limb injuries are common in racing horses and track surface properties have been associated with injury risk. To better understand how track surfaces may contribute to equine limb injury, we developed the first 3D computational model of the equine hoof interacting with a racetrack and simulated interactions with model representations of 1) a dirt surface and 2) an all-weather synthetic track. First, a computational track model using the Smoothed Particle Hydrodynamics (SPH) method with a Drucker-Prager (D-P) elastoplastic material model was developed. It was validated against analytical models and published data and then calibrated using results of a custom track testing device applied to the two racetrack types. Second, a sensitivity analysis was performed to determine which model parameters contribute most significantly to the mechanical response of the track under impact-type loading. Third, the SPH track model was coupled to a biomechanical model of the horse forelimb and applied to hoof-track impact for a horse galloping on each track surface. We found that 1) the SPH track model was well validated and it could be calibrated to accurately represent impact loading of racetrack surfaces at two angles of impact; 2) the amount of harrowing applied to the track had the largest effect on impact loading, followed by elastic modulus and cohesion; 3) the model is able to accurately simulate hoof-ground interaction and enables study of the relationship between track surface parameters and the loading on horses' distal forelimbs.

Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine.

It is safe to say that global capitalism has created the conditions for a more liberal market as well as free interchange among nations. This particularly pivoted in the rise and expansion of tourism, but at the same time, it made things harder for the destinations in view of a climate of excessive competition. This chapter brings some reflection on how educating tourists to visit destinations is mainly marked by an ongoing state of political violence and instability. The thesis held by the authors stands for tourism education avoids long-dormant ethnocentric discourses based on the fear of traveling to so-called risky destinations. This begs the question to what extent behind the alarmism of tourism safety and security lies deep western ethnocentrism.

Although tourism marketing and management have gained firm positions over the recent years, no less true seems to be that the rules of marketing have been put upside down just after the pandemic. The DMO model has been proven to be efficient in recycling destinations in the context of crisis and chaos. This chapter delves into the world of national identities and heritage as key factors of national cohesion and unity. Having said this, the DMO model helps readers to expand their understanding of tourist preferences as well as the narratives emanating from the core of nations and sold as national heritage.

Background and Aims: It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. Methods: We conducted three web-based surveys among stroke physicians in Scandinavia and the United Kingdom. Results: Eighty-nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. Conclusion: Considerable proportions of stroke physicians in Scandinavia and the United Kingdom were uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials.

Background and Aims: It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. Methods: We conducted three web-based surveys among stroke physicians in Scandinavia and the United Kingdom. Results: Eighty-nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. Conclusion: Considerable proportions of stroke physicians in Scandinavia and the United Kingdom were uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials.