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Effects of semaglutide in obesity-related heart failure with preserved ejection fraction across the age spectrum: findings from the STEP-HFpEF programme
Get PDFBackground:
The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with age, and older adults with HFpEF have worse physical function, quality of life, and clinical outcomes. Semaglutide demonstrated efficacy in the treatment of obesity‐related HFpEF in the STEP‐HFpEF trials. Some have speculated that older patients may have less to gain from incretin therapies (and perhaps more to lose) than younger patients.
Aims:
In this pre‐specified pooled subanalysis of the STEP‐HFpEF trials, we evaluated the efficacy of semaglutide across the age spectrum.
Methods:
The STEP‐HFpEF and STEP‐HFpEF DM trials enrolled participants with obesity‐related HFpEF and randomized them to semaglutide 2.4 mg once weekly ( n = 573) or placebo ( n = 572) for 52 weeks. Dual primary outcomes (change in Kansas City Cardiomyopathy Questionnaire clinical summary score [KCCQ‐CSS] and change in body weight) and secondary outcome measures (6‐minute walk distance [6MWD], C‐reactive protein, hierarchical composite endpoint containing all‐cause death, heart failure events, changes in KCCQ‐CSS and 6MWD) were compared across specific age groups; <55 years, 55–64 years, 65–74 years and ≥75 years.
Results:
Among 1145 randomized participants, 8.8% ( N = 101) were <55, 23.3% ( N = 267) were aged between 55–64, 42.4% ( N = 485) were between 65–74, and 25.5% ( N = 292) were 75 years or over. The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ‐CSS ( p ‐interaction = 0.80), and body weight ( p ‐interaction = 0.41). Similar benefits were observed for the key secondary endpoints, with no treatment effect heterogeneity across age groups. Moreover, the safety of semaglutide was consistent across age groups.
Conclusion:
In patients with HFpEF enrolled across the STEP‐HFpEF and STEP‐HFpEF DM trials, treatment with semaglutide improved disease‐specific symptoms, physical function and reduced body weight across the age spectrum. The safety profile of semaglutide was consistent in older and younger patients
The importance of nature in children's development
No full textTraditional early childhood education (ECE) settings are typically characterised by children spending most of their time indoors and when they are outdoors the playground tends to have limited integration of natural elements, such as trees and woodland areas, varied topography, and vegetation with a variety of trees, rocks, fallen logs, and loose parts. On the contrary, in nature-based ECE, nature is integrated into the philosophy, curriculum, and/or wider environment, and children typically spend most of their day outdoors in immersive nature experiences. The opportunity to explore the concepts of Learning to Move and Moving to Learn is enhanced beyond the traditional approach to teaching physical education. This is due to the wide affordances the natural environment provides in achieving physical competence, in addition to the wider social, emotional, and cognitive outcomes that physical education seeks to achieve
Harnessing generative artificial intelligence to advance education for sustainable development
Get PDFIn this paper we report on a study of the impact of the CoDesignS ESD AI Coach on academic and practitioner perspectives regarding the integration of Education for Sustainable Development (ESD) within teaching and curriculum design. Employing activity theory as the analytical framework, we investigate both the opportunities and limitations associated with the use of generative AI (GenAI) in educational contexts to support ESD.
Eighteen participants from a range of higher education (HE) institutions in the UK engaged in the research through a workshop setting. The cohort represented a breadth of disciplinary backgrounds, including engineering, medical sciences, sustainability and veterinary sciences.
The workshop introduced participants to concepts of sustainability and ESD, followed by the CoDesignS ESD Framework and its Role, Objective, Community, Key, Shape (ROCKS) method for effective prompting.
We employed a mixed-methods research design, incorporating pre-and-post surveys alongside focus groups. Discussion focused on the extent to which the tool enhanced or hindered participants’ understanding of sustainability concepts, and how well it aligned with disciplinary expectations. Reflections also addressed the perceived relevance and accuracy of GenAI-generated content.
Survey data revealed that participants felt more confident and better equipped with resources to embed sustainability into their curriculum, and they reported increased assurance in using GenAI tools for curriculum development.
Based on focus group analysis, we conclude that the CoDesignS ESD AI Coach holds particular value as a prompt for idea generation. However, it should not be used in isolation. Those specialising in sustainability and curriculum design should guide its effective implementation
Co-developing best bets for participatory disaster risk management in a postcolonial harmscape
No full textThe conditions that characterise marginal and informal settlements in the Global South make the environmental hazards resulting from the current Climate Crisis more dangerous, giving rise to multifaceted risks that can be characterised as Anthropocene harmscapes. As such settlements are home to a large and growing population, this is an increasingly widespread problem that, if not addressed, could result in deaths, unrest and increasing numbers of climate refugees. Recognizing that neither climate change nor informality are going to disappear, it is essential to find practicable, contextualised and locally appropriate ways of mitigating and coping with climate change-exacerbated risks such as water scarcity, floods and fires. This paper describes a co-research process intended to enable residents of at-risk settlements to mobilize their own knowledges and experiences to identify and articulate strategies with a realistic potential for practical implementation. It demonstrates how this process yielded suggestions for actions that operate at a range of scales, from small changes to everyday practices that can be accomplished by individuals and households to infrastructural improvements that need cooperation and resourcing from local or national authorities. It also demonstrates some of the limitations of decolonial approaches that uniquely prioritize local knowledges when attempting to address challenges with global origins
From the gut to the brain: potential novel avenues for IBD treatment via serotonergic pathways
Get PDFInflammatory bowel disease (IBD) is an idiopathic condition characterised by chronic relapsing intestinal inflammation, affecting approximately 6.8 million people globally. Crohn’s disease and ulcerative colitis are two main subtypes. The microbiota in IBD patients has been extensively researched, and dysbiosis is associated with IBD onset. While current treatments reduce morbidity and improve the quality of life of IBD patients, they have strong anti-inflammatory effects, creating an immunosuppressed environment and increase the risk of comorbidities, highlighting the need for better therapeutics. The gut-brain axis (GBA) communication pathway allows bidirectional neural, hormonal, metabolic, immunological and microbial signalling. This review investigates the signalling pathways across the GBA and explores how dysbiosis, neuroinflammation and serotonergic dysregulation are interlinked and may contribute to IBD pathogenesis and neurological comorbidities. Focusing on the immunomodulation of serotonergic signalling and proposed mechanisms of action of psychotropic drugs, including antidepressants and psychedelic compounds, we highlight the serotonergic signalling pathway as a potential novel therapeutic target for IBD combination therapy
Observation of orbitally excited Bc+ states
Get PDFThe observation of a wide peaking structure in the B c + γ mass spectrum is reported using proton-proton collision data collected by the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9 fb − 1 . The statistical significance over the background-only hypothesis exceeds seven standard deviations. The width of the observed structure is larger than the expectation from a single-peak hypothesis, and is well described by an effective minimal model consisting of two narrow peaks located at 6704.8 ± 5.5 ± 2.8 ± 0.3 MeV / c 2 and 6752.4 ± 9.5 ± 3.1 ± 0.3 MeV / c 2 . The uncertainty terms are statistical, systematic, and associated to the knowledge of the B c + mass, respectively. The measured peak locations are in line with theoretical predictions for lowest excited P -wave B c + states, marking the first observation of orbitally excited beauty-charm mesons and providing important insights into the internal dynamics of hadrons containing two heavy quarks
What are the factors that can challenge and promote resilience in parents of children with intellectual disabilities?
Get PDFBackground:
Raising a child with intellectual disabilities poses significant challenges. Despite the challenges faced by parents of children with intellectual disabilities, resilient parents can maintain a positive outlook and effectively navigate these challenges, whereas others struggle. This systematic review contributes to the literature by synthesising research on the factors influencing resilience among parents of children with intellectual disabilities.
Methods:
Searches were conducted using databases MEDLINE, PsycINFO, EMBASE, CINAHL and SocINDEX. Reference lists of all included articles were searched. Quality assessments were performed using CASP.
Results:
Of the 6382 studies identified, 27 were included in the review. A narrative synthesis of the included studies was performed. The study details were organised into two main factors: personal and contextual.
Conclusion:
This systematic review highlights the need to promote the resilience of parents of children with intellectual disabilities. Evidence suggests that a combination of personal and contextual factors contributes to parental resilience
Coagulative granular hydrogels with an enzyme catalyzed fibrin network for endogenous tissue regeneration
Get PDFGranular hydrogels, composed of densely packed microgels, are an emerging class of injectable microporous scaffolds that provide interstitial porosity for endogenous cell recruitment and tissue repair. However, weak bonding interactions between constituent microgels compromise the mechanical integrity of these biomaterials, limiting their scope and effectiveness for in vivo applications where structural support is required. To address this challenge, we introduce a new bioinspired stabilization method and a novel class of regenerative biomaterial: coagulative granular hydrogels, assembled from thrombin-functionalized gelatin methacryloyl microgels. The surface-bound thrombin is enzymatically active and catalyzes the conversion of fibrinogen into a fibrin hydrogel that extends throughout the interstitial voids of the granular hydrogel. This secondary network acts as a biological glue to stabilize the granular hydrogel, yielding shear and compressive properties comparable to bulk hydrogel controls. Furthermore, the interstitial fibrin network provides a favorable microenvironment for the adhesion, proliferation, and invasion of endothelial cells, highlighting the potential of the biomaterial to support endogenous tissue repair. Subcutaneous injection in mice showed that the coagulative granular hydrogels preserved structural integrity and supported fibrin deposition, cell infiltration, and collagen remodeling in vivo. Future work will adapt this technology to other biomaterials and validate its performance for different tissue repair applications
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