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A data collection programme for improving healthcare in UK human spaceflight venturesOver the next decade the number of humans venturing beyond Earth is projected to rapidly increase in both quantity and diversity. Humans will regularly fly to the International Space Station until it is decommissioned by 2031, will return to the Moon by 2025 via the Artemis programme, and will fly to space via commercial ventures. Spaceflight presents a hazardous environment for human health. To understand spaceflight-associated health risks further and to increase safety via advanced healthcare approaches, including personalised medicine, more data must be collected. Importantly, this data must be derived from a diverse cohort of participants and a range of mission formats. We propose that the UK should start to consider all citizens venturing into space as potential participants from which health and biological data could be consensually collected. Importantly, we believe that this routine data collection programme should adopt a similar strategy to the UK National Health Service and the UK Biobank, by including "omics" data for scientific and healthcare purposes. We consider how such a world-leading programme, kick-started via a pilot study, might be realised through appropriate policy design, including which measures to collect, when to collect them, and unique ethical considerations pertaining to the spacefaring population.
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Mitochondrial sulfide promotes life span and health span through distinct mechanisms in developing versus adult treated Caenorhabditis elegansLiving longer without simultaneously extending years spent in good health ("health span") is an increasing societal burden, demanding new therapeutic strategies. Hydrogen sulfide (H2S) can correct disease-related mitochondrial metabolic deficiencies, and supraphysiological H2S concentrations can pro health span. However, the efficacy and mechanisms of mitochondrion-targeted sulfide delivery molecules (mtH2S) administered across the adult life course are unknown. Using a Caenorhabditis elegans aging model, we compared untargeted H2S (NaGYY4137, 100 µM and 100 nM) and mtH2S (AP39, 100 nM) donor effects on life span, neuromuscular health span, and mitochondrial integrity. H2S donors were administered from birth or in young/middle-aged animals (day 0, 2, or 4 postadulthood). RNAi pharmacogenetic interventions and transcriptomics/network analysis explored molecular events governing mtH2S donor-mediated health span. Developmentally administered mtH2S (100 nM) improved life/health span vs. equivalent untargeted H2S doses. mtH2S preserved aging mitochondrial structure, content (citrate synthase activity) and neuromuscular strength. Knockdown of H2S metabolism enzymes and FoxO/daf-16 prevented the positive health span effects of mtH2S, whereas DCAF11/wdr-23 - Nrf2/skn-1 oxidative stress protection pathways were dispensable. Health span, but not life span, increased with all adult-onset mtH2S treatments. Adult mtH2S treatment also rejuvenated aging transcriptomes by minimizing expression declines of mitochondria and cytoskeletal components, and peroxisome metabolism hub components, under mechanistic control by the elt-6/elt-3 transcription factor circuit. H2S health span extension likely acts at the mitochondrial level, the mechanisms of which dissociate from life span across adult vs. developmental treatment timings. The small mtH2S doses required for health span extension, combined with efficacy in adult animals, suggest mtH2S is a potential healthy aging therapeutic.
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Caenorhabditis elegans in microgravity: An omics perspectiveThe application of omics to study Caenorhabditis elegans (C. elegans) in the context of spaceflight is increasing, illuminating the wide-ranging biological impacts of spaceflight on physiology. In this review, we highlight the application of omics, including transcriptomics, genomics, proteomics, multi-omics, and integrated omics in the study of spaceflown C. elegans, and discuss the impact, use, and future direction of this branch of research. We highlight the variety of molecular alterations that occur in response to spaceflight, most notably changes in metabolic and neuromuscular gene regulation. These transcriptional features are reproducible and evident across many spaceflown species (e.g., mice and astronauts), supporting the use of C. elegans as a model organism to study spaceflight physiology with translational capital. Integrating tissue-specific, spatial, and multi-omics approaches, which quantitatively link molecular responses to phenotypic adaptations, will facilitate the identification of candidate regulatory molecules for therapeutic intervention and thus represents the next frontiers in C. elegans space omics research.
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Synthesis and biological evaluation of cyclobutane-based β3 integrin antagonists: A novel approach to targeting integrins for cancer therapyThe Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.
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Improved learning outcomes and teacher experience: A qualitative study of team-based learning in secondary schoolsBased on the benefits of Team-Based Learning (TBL) in higher education, our project investigated possible benefits of TBL in secondary education. We found that, despite challenges, the benefits of using TBL in secondary schools make it worth teachers’ time and effort. We conducted a year-long qualitative study with 13 teachers from Ireland, Spain and UK. While teachers found preparation time, institutional requirements, and managing student team dynamics challenging, challenges were outweighed by benefits including improved student engagement, quality of learning, skill development, and teacher job satisfaction. We recommend further TBL training for secondary-level teachers and further research into this topic
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The early lives of the Islanders: Stable isotope analysis of incremental dentine collagen from the prehispanic period of the Canary IslandsObjectives: This study presents isotopic information for incremental dentine collagen and bone bulk collagen from individuals from the Canary Islands (Tenerife and Gran Canaria) to explore dietary differences during childhood life. Materials and Methods: Eight individuals have been studied, which comprises 122 δ15N and δ13C incremental dentine measurements and eight bulk bone collagen analyses. A baseline of potentially consumed food sources has been developed for comparative purposes. A FRUITS model of probable contributions of each food source towards the diet of each individual has been developed. All samples but one belongs to the later period of indigenous occupation of the archipelago. Results: The dentine collagen data are presented in correlated δ13C and δ15N plots per individual, showing the isotopic changes throughout time. δ15N values for each individual tend to be variable whereas δ13C data are generally more stable with a range of +9.1 to +14‰ for δ15N and –17.4 to –20.8‰ for δ13C. Conclusion: The isotopic analysis allows for the reconstruction of 8 dietary profiles, which allow us to estimate the different dietary protein sources. The FRUITS model shows different percentages of the primary food sources for each individual. Where both δ13C and δ15N are elevated, this could be indicative of a higher marine contribution to the diet. There appear to be two main dietary profiles identifiable in the dataset and these may be related to changes in status or place of residence. Short-term variations in δ13C and δ15N and opposing co-variance of isotopic values can be indicative of nutritional stress, although metabolic changes during growth are also considered.
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Metal-Free Oxyacetoxylation of Arylynamines and Ynamides to Construct α-Acetoxyl AmidesYnamides/arylynamines are challenging substrates for oxyacetoxylation, especially due to various reactive sites of N-heteroaryl ring. Herein we report a metal-free PhI(OAc)2-mediated oxyacetoxylation of arylynamines / ynamides to provide α-acetoxyl amides in good to excellent yields. The transformation completes in a short time to afford solely the product without functionalising N-heteroaryl moiety, in a highly regio- and chemo-selective manner through β-iodo keteneiminium intermediate.
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Survey on Opportunity Management as part of Project Risk ManagementThe project to set-up the survey in this dataset was supported by the Association for Project Management (APM), and the survey has been sent sent to its corporate member organisations. The survey was intended to help to gain a better understanding of the policies and practice around Opportunity Management as a part of Project Risk Management. The survey has been designed and analysed by members of the APM Risk SIG and Delft University of Technology (The Netherlands). Results of the survey have been presented to APM to help the development of APM's documented approach to Project Risk Management in publications such as the APM Body of Knowledge and SIG Guides. In addition, anonymous and aggregated survey results are used for academic publications, providing more insight into the practice of Opportunity Management. The dataset contains: - Survey questions as they have been entered into Qualtrics (TM) [PDF] - Coding scheme that has been used to code the answers to the survey questions [PDF] - Raw answers to the survey questions (fully anonymized) [CSV] - Data Management Plan (DMP) for the survey as part of the HREC application [PDF] - HREC approval from TU Delft for the research protocol [PDF] - readme.txt file with this content
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Suprathreshold Approaches to Mapping the Visual Field in Advanced GlaucomaMeasuring the spatial extent of defects may be advantageous in advanced glaucoma where conventional perimetric sensitivity measurements are unreliable. We test whether suprathreshold tests on a higher density grid can more efficiently map advanced visual field loss. Data from 97 patients with mean deviation
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Understanding Disability and Physical Impairment in Early Medieval England: an Integration of Osteoarchaeological and Funerary EvidenceTHIS PAPER INVESTIGATES physical impairment and disability in the c 5th to 6th centuries ad in England through a combination of osteological and funerary analyses. A total of 1,261 individuals, 33 of whom had osteologically identifiable physical impairment, from nine early medieval cemeteries were included. The funerary data for all individuals in each cemetery was collected, and the individuals with physical impairment were analysed palaeopathologically. The burial treatment of individuals with and without physical impairment was compared both quantitatively and qualitatively, and patterns within and between cemeteries were explored to investigate contemporary perceptions and understandings of impairment and disability. The results suggest that some people with physical impairment and potential disability were buried with treatment that was arguably positive, while others were buried with treatment that was either normative or potentially negative. This suggests that, in the same way as the rest of the community, individuals with physical impairment and potential disability had a variety of identities (that may or may not have been influenced by their impairment or disability) and could occupy different social spaces/statuses.
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Exploring variation in implementation of multifactorial falls risk assessment and tailored interventions: a realist reviewFalls are the most common safety incident reported by acute hospitals. In England national guidance recommends delivery of a multifactorial falls risk assessment (MFRA) and interventions tailored to address individual falls risk factors. However, there is variation in how these practices are implemented. This study aimed to explore the variation by examining what supports or constrains delivery of MFRAs and tailored interventions in acute hospitals. A realist review of literature was conducted with searches completed in three stages: (1) to construct hypotheses in the form of Context, Mechanism, Outcome configurations (CMOc) about how MFRAs and interventions are delivered, (2) to scope the breadth and depth of evidence available in Embase to test the CMOcs, and (3) following prioritisation of CMOcs, to refine search strategies for use in multiple databases. Citations were managed in EndNote; titles, abstracts, and full texts were screened, with 10% independently screened by two reviewers. Two CMOcs were prioritised for testing labelled: Facilitation via MFRA tools, and Patient Participation in interventions. Analysis indicated that MFRA tools can prompt action, but the number and type of falls risk factors included in tools differ across organisations leading to variation in practice. Furthermore, the extent to which tools work as prompts is influenced by complex ward conditions such as changes in patient condition, bed swaps, and availability of falls prevention interventions. Patient participation in falls prevention interventions is more likely where patient directed messaging takes individual circumstances into account, e.g., not wanting to disturb nurses by using the call bell. However, interactions that elicit individual circumstances can be resource intensive and patients with cognitive impairment may not be able to participate despite appropriately directed messaging. Organisations should consider how tools can be developed in ways that better support consistent and comprehensive identification of patients' individual falls risk factors and the complex ward conditions that can disrupt how tools work as facilitators. Ward staff should be supported to deliver patient directed messaging that is informed by their individual circumstances to encourage participation in falls prevention interventions, where appropriate. PROSPERO: CRD42020184458.
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The extent of anticholinergic burden across an older Welsh population living with frailty: Cross-sectional analysis of general practice recordsBackground: Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (1) investigate the prevalence of anticholinergic prescribing for older patients, and (2) examine anticholinergic burden according to frailty status. Methods: Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage (SAIL) databank including patients aged ≥65 at their first GP consultation between 1st January and 31st December 2018. Frailty was identified using the electronic Frailty Index (eFI) and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to 1) describe the type and frequency of anticholinergics prescribed; 2) to estimate the association between frailty and cumulative ACB score (ACB-Sum). Results: In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared to patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061–1.064), moderate frailty, adj OR 1.134 (95%CI 1.131–1.136), severe frailty, adj OR 1.208 (95%CI 1.203–1.213)). Conclusions: Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications given the risks of functional and cognitive decline that frailty presents.
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A Rule-Based Predictive Model for Estimating Human Impact Data in Natural Onset Disasters - The Case of PRED ModelThis paper proposes a framework to cope with the lack of data at the time of a disaster by em-ploying predictive models. The framework can be used for disaster human impact assessment based on the socio-economic characteristics of the affected countries. A panel data of 4252 natural onset disasters between 1980 to 2020 is processed through concept drift phenomenon and rule-based classifiers, namely Moving Average (MA). A Predictive model for Estimating Data (PRED) is developed as a decision-making platform based on the Disaster Severity Analysis (DSA) Technique. A comparison with the real data shows that the platform can predict the human impact of a disaster (fatality, injured, homeless) up to 3% errors; thus, it is able to inform the selection of disaster relief partners for various disaster scenarios.
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Archaeologists discover ancient Mayan board game – here’s what it can teach modern educatorsArchaeologists have unearthed a stone scoreboard in Chichén Itzá, Mexico, shedding light on the Mayan civilization's ancient board game called Pok-a-Tok. The Mayan games held deep cultural and religious significance, reflecting the beliefs and values of the people. Winning such games was considered a sign of divine favor, while losing could result in human sacrifices. Mayan games fostered communal identity and connections between the physical, spiritual, and social realms. The concept of the "magic circle" in gaming, where players enter a temporary world with its own rules and boundaries, can be applied to modern education to promote inclusion, collaboration, and the development of critical thinking and problem-solving skills. By incorporating ancient and modern games, educators can create inclusive learning environments that cater to diverse student needs.
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Barriers and enablers to healthcare system uptake of direct oral anticoagulants for stroke prevention in atrial fibrillation: a qualitative interview study with healthcare professionals and policy makers in EnglandObjective: To better understand the factors influencing the uptake of direct oral anticoagulants (DOACs) across different health economies in National Health Service England from the perspective of health professionals and other health economy stakeholders. Design: Qualitative interview study using a critical realism perspective and informed by the Diffusion of Innovations in Service Organisations model. Setting: Three health economies in the North of England, United Kingdom. Participants: Healthcare professionals involved in the management of patients requiring oral anticoagulants, stakeholders involved in the implementation of DOACs and representatives of pharmaceutical industry companies and patient support groups. Intervention: Semistructured interviews (face-to-face or telephone) were conducted with 46 participants. Interviews were analysed using the Framework method. Results: Identified factors having an impact on the uptake of DOACs were grouped into four themes: perceived value of the innovation, clinician practice environment, local health economy readiness for change, and the external health service context. Together, these factors influenced what therapy options were offered and prescribed to patients with atrial fibrillation. The interviews also highlighted strategies used to improve or restrict the uptake of DOACs and tensions between providing patient-centred care and managing financial implications for commissioners. Conclusions: The findings contribute to the wider literature by providing a new and in-depth understanding on the uptake of DOACs. The findings may be applicable to other new medicines used in chronic health conditions.
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Can Personality Traits Predict Students’ Satisfaction with Blended Learning during the COVID-19 Pandemic?The present study aimed to assess the impact of personality traits on student satisfaction with blended learning which many higher education institutions have adopted since the COVID-19 pandemic in the UK. Personality traits were assessed using the International Personality Item Pool and student satisfaction was recorded on a 7-point Likert scale. Data analysis of 72 undergraduate students revealed that low extraversion and high neuroticism predicted higher levels of student satisfaction. Implications are discussed considering the current pandemic with a view of increasing student satisfaction and in-turn improving National Student Survey results that impact on Teaching Excellence Framework scores and league tables.
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Viewing Contact Sports as a Safeguarding Issue... Sustaining a sport-related concussion (SRC) has been associated with negative consequences to emotion and cognition in recent years,4,5 and head impacts are no different.1 Moreover, there is a consistent link reported with neurodegenerative diseases such as motor-neuron disease, Parkinson’s disease, and dementia. Although this is well-known within the scientific community, and becoming so in the general population, we still place children at risk. Promoting attitude change toward SRC and head impacts in sport is difficult enough with adults as many are accustomed to the way their contact sports are played and spectated. However, a redeeming feature for many researchers is that the evidence is there, and the rhetoric is being discussed in the mainstream media across the world.
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Providing a clearer insight into how sport-related concussion and physical pain impact mental health, cognition, and quality of lifeSport-related concussion (SRC) and physical pain are both associated with poor mental health, impaired cognition, and reduced quality of life. Despite SRC and physical pain often co-occurring, there is little research that investigates these two factors together, and therefore it is difficult to conclude which of these contributes to the negative outcomes asso ciated with them. Therefore, the present study aimed to investigate the effect of SRC and physical pain on mental health, cognitive ability, and quality of life. Depression was measured using the Center for Epidemiological Studies Depression Scale, anxiety was assessed using the State-Trait Anxiety Inventory while the SF-12 recorded health-related quality of life. A trail making task (TMT) assessed cognitive flexibility of participants. Analysis of 83 participants (43 concussed) revealed that SRC led to reduced accuracy on TMT(A) and (B), whereas physical pain was responsible for poorer mental health and reduced quality of life. This study highlights the influence that SRC has on cognitive ability and the impact that physical pain has on mental health and quality of life. With this information, we are better placed to predict the negative consequences of SRC and physical pain and therefore tailor support accordingly.
