140 research outputs found

    Using Bayesian Networks to Investigate the Influence of Subseasonal Arctic Variability on Midlatitude North Atlantic Circulation

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    Recent enhanced warming and sea ice depletion in the Arctic have been put forward as potential drivers of severe weather in the midlatitudes. Evidence of a link between Arctic warming and midlatitude atmospheric circulation is growing, but the role of Arctic processes relative to other drivers remains unknown. Arctic–midlatitude connections in the North Atlantic region are particularly complex but important due to the frequent occurrence of severe winters in recent decades. Here, dynamic Bayesian networks with hidden variables are introduced to the field to assess their suitability for teleconnection analyses. Climate networks are constructed to analyze North Atlantic circulation variability at 5-day to monthly time scales during the winter months of the years 1981–2018. The inclusion of a number of Arctic, midlatitude, and tropical variables allows for an investigation into the relative role of Arctic influence compared to internal atmospheric variability and other remote drivers. A robust covariability between regions of amplified Arctic warming and two definitions of midlatitude circulation is found to occur entirely within winter at submonthly time scales. Hidden variables incorporated in networks represent two distinct modes of stratospheric polar vortex variability, capturing a periodic shift between average conditions and slower anomalous flow. The influence of the Barents–Kara Seas region on the North Atlantic Oscillation is found to be the strongest link at 5- and 10-day averages, while the stratospheric polar vortex strongly influences jet variability on monthly time scales

    An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba dictyostelium discoideum

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    Mutations in either of two presenilin genes can cause familial Alzheimer's disease. Presenilins have both proteolysis-dependent functions, as components of the γ-secretase complex, and proteolysis-independent functions in signalling. In this study, we investigate a conserved function of human presenilins in the development of the simple model organism Dictyostelium discoideum. We show that the block in Dictyostelium development caused by the ablation of both Dictyostelium presenilins is rescued by the expression of human presenilin 1, restoring the terminal differentiation of multiple cell types. This developmental role is independent of proteolytic activity, because the mutation of both catalytic aspartates does not affect presenilin ability to rescue development, and the ablation of nicastrin, a γ-secretase component that is crucial for proteolytic activity, does not block development. The role of presenilins during Dictyostelium development is therefore independent of their proteolytic activity. However, presenilin loss in Dictyostelium results in elevated cyclic AMP (cAMP) levels and enhanced stimulation-induced calcium release, suggesting that presenilins regulate these intracellular signalling pathways. Our data suggest that presenilin proteins perform an ancient non-proteolytic role in regulating intracellular signalling and development, and that Dictyostelium is a useful model for analysing human presenilin function

    Maintaining independence in individuals with dementia at home after a fall: a protocol for the UK pilot cluster randomised controlled trial MAINTAIN

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    \ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Introduction Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual\u27s overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia. Method and analysis This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes. Ethics and dissemination The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals. Trial registration number ISRCTN16413728

    Microbes in beach sands : integrating environment, ecology and public health

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    Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Reviews in Environmental Science and Bio/Technology 13 (2014): 329-368, doi:10.1007/s11157-014-9340-8.Beach sand is a habitat that supports many microbes, including viruses, bacteria, fungi and protozoa (micropsammon). The apparently inhospitable conditions of beach sand environments belie the thriving communities found there. Physical factors, such as water availability and protection from insolation; biological factors, such as competition, predation, and biofilm formation; and nutrient availability all contribute to the characteristics of the micropsammon. Sand microbial communities include autochthonous species/phylotypes indigenous to the environment. Allochthonous microbes, including fecal indicator bacteria (FIB) and waterborne pathogens, are deposited via waves, runoff, air, or animals. The fate of these microbes ranges from death, to transient persistence and/or replication, to establishment of thriving populations (naturalization) and integration in the autochthonous community. Transport of the micropsammon within the habitat occurs both horizontally across the beach, and vertically from the sand surface and ground water table, as well as at various scales including interstitial flow within sand pores, sediment transport for particle-associated microbes, and the large-scale processes of wave action and terrestrial runoff. The concept of beach sand as a microbial habitat and reservoir of FIB and pathogens has begun to influence our thinking about human health effects associated with sand exposure and recreational water use. A variety of pathogens have been reported from beach sands, and recent epidemiology studies have found some evidence of health risks associated with sand exposure. Persistent or replicating populations of FIB and enteric pathogens have consequences for watershed/beach management strategies and regulatory standards for safe beaches. This review summarizes our understanding of the community structure, ecology, fate, transport, and public health implications of microbes in beach sand. It concludes with recommendations for future work in this vastly under-studied area.2015-05-0

    Maintaining independence in individuals with dementia at home after a fall:a protocol for the UK pilot cluster randomised controlled trial MAINTAIN

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    Introduction: Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual’s overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia. Method and analysis: This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes. Ethics and dissemination: The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals. Trial registration number: ISRCTN16413728

    A rehabilitation intervention to improve recovery after an episode of delirium in adults over 65 years (RecoverED): study protocol for a multi-centre, single-arm feasibility study

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    Background: Delirium affects over 20% of all hospitalised older adults. Delirium is associated with a number of adverse outcomes following hospital admission including cognitive decline, anxiety and depression, increased mortality and care needs. Previous research has addressed prevention of delirium in hospitals and care homes, and there are guidelines on short-term treatment of delirium during admission. However, no studies have addressed the problem of longer-term recovery after delirium and it is currently unknown whether interventions to improve recovery after delirium are effective and cost-effective. The primary objective of this feasibility study is to test a new, theory-informed rehabilitation intervention (RecoverED) in older adults delivered following a hospital admission complicated by delirium to determine whether (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible. Methods: The study is a multi-centre, single-arm feasibility study of a rehabilitation intervention with an embedded process evaluation. Sixty participants with delirium (aged > 65 years old) and carer pairs will be recruited from six NHS acute hospitals across the UK. All pairs will be offered the intervention, with follow-up assessments conducted at 3 months and 6 months post-discharge home. The intervention will be delivered in participants’ own homes by therapists and rehabilitation support workers for up to 10 intervention sessions over 12 weeks. The intervention will be tailored to individual needs, and the chosen intervention plan and goals will be discussed and agreed with participants and carers. Quantitative data on reach, retention, fidelity and dose will be collected and summarised using descriptive statistics. The feasibility outcomes that will be used to determine whether the study meets the criteria for progression to a definitive randomised controlled trial (RCT) include recruitment, delivery of the intervention, retention, data collection and acceptability of outcome measures. Acceptability of the intervention will be assessed using in-depth, semi-structured qualitative interviews with participants and healthcare professionals. Discussion: Findings will inform the design of a pragmatic multi-centre RCT of the effectiveness and cost-effectiveness of the RecoverED intervention for helping the longer-term recovery of people with delirium compared to usual care. Trial registration: The feasibility study was registered: ISRCTN1567657

    Hugs and behaviour points: alternative education and the regulation of 'excluded' youth

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    In England, alternative education (AE) is offered to young people formally excluded from school, close to formal exclusion or who have been informally pushed to the educational edges of their local school. Their behaviour is seen as needing to change. In this paper, we examine the behavioural regimes at work in 11 AE programmes. Contrary to previous studies and the extensive ‘best practice’ literature, we found a return to highly behaviourist routines, with talking therapeutic approaches largely operating within this Skinnerian frame. We also saw young people offered a curriculum largely devoid of languages, humanities and social sciences. What was crucial to AE providers, we argue, was that they could demonstrate 'progress' in both learning and behaviour to inspectors and systems. Mobilising insights from Foucault, we note the congruence between the external regimes of reward and punishment used in AE and the kinds of insecure work and carceral futures that might be on offer to this group of young people

    Quality and reporting standards, resources, training materials and information for realist evaluation: the RAMESES II project

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    Background: Many of the problems confronting policy- and decision-makers, evaluators and researchers today are complex, as are the interventions designed to tackle them. Their success depends both on individuals’ responses and on the wider context of people’s lives. Realist evaluation tries to make sense of these complex interventions. It is a form of theory-driven evaluation, based on realist philosophy that aims to understand why these complex interventions work, how, for whom, in what context and to what extent. Objectives: Our objectives were to develop (a) quality standards, (b) reporting standards, (c) resources and training materials, (d) information and resources for patients and other lay participants and (e) to build research capacity among those interested in realist evaluation. Methods: To develop the quality and reporting standards, we undertook a thematic review of the literature, supplemented by our content expertise and feedback from presentations and workshops. We synthesised findings into briefing materials for realist evaluations for the Delphi panel (a structured method using experts to develop consensus). To develop our resources and training materials, we drew on our experience in developing and delivering education materials, feedback from the Delphi panel, the RAMESES JISCMail e-mail list, training workshops and feedback from training sessions. To develop information and resources for patients and other lay participants in realist evaluation, we convened a group consisting of patients and the public. We built research capacity by running workshops and training sessions. Results: Our literature review identified 152 realist evaluations, and when 37 of these had been analysed we were able to develop our briefing materials for the Delphi panel. The Delphi panel comprised 35 members from 27 organisations across six countries and five disciplines. Within three rounds, the panels had reached a consensus on 20 key reporting standards. The quality standards consist of eight criteria for realist evaluations. We developed resources and training materials for 15 theoretical and methodological topics. All resources are available online (www.ramesesproject.org). We provided methodological support to 17 projects and presentations or workshops to help build research capacity in realist evaluations to 29 organisations. Finally, we produced a generic patient information leaflet for lay participants in realist evaluations. Limitations: Our project had ambitious goals that created a substantial workload, leading to the need to prioritise objectives. For example, we truncated the literature review and focused on standards and training material development. Conclusions: Although realist evaluation holds much promise, misunderstandings and misapplications of it are common. We hope that our project’s outputs and activities will help to address these problems. Our resources are the start of an iterative journey of refinement and development of better resources for realist evaluations. The RAMESES II project seeks not to produce the last word on these issues, but to capture current expertise and establish an agreed state of the science. Much methodological development is needed in realist evaluation but this can take place only if there is a sufficient pool of highly skilled realist evaluators. Capacity building is the next key step in realist evaluation. Funding: The National Institute for Health Research Health Services and Delivery Research programme

    Development of a UK core dataset for geriatric medicine research: a position statement and results from a Delphi consensus process

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    BACKGROUND: There is lack of standardisation in assessment tools used in geriatric medicine research, which makes pooling of data and cross-study comparisons difficult. METHODS: We conducted a modified Delphi process to establish measures to be included within core and extended datasets for geriatric medicine research in the United Kingdom (UK). This included three complete questionnaire rounds, and one consensus meeting. Participants were selected from attendance at the NIHR Newcastle Biomedical Research Centre meeting, May 2019, and academic geriatric medicine e-mailing lists. Literature review was used to develop the initial questionnaire, with all responses then included in the second questionnaire. The third questionnaire used refined options from the second questionnaire with response ranking. RESULTS: Ninety-eight responses were obtained across all questionnaire rounds (Initial: 19, Second: 21, Third: 58) from experienced and early career researchers in geriatric medicine. The initial questionnaire included 18 questions with short text responses, including one question for responders to suggest additional items. Twenty-six questions were included in the second questionnaire, with 108 within category options. The third questionnaire included three ranking, seven final agreement, and four binary option questions. Results were discussed at the consensus meeting. In our position statement, the final consensus dataset includes six core domains: demographics (age, gender, ethnicity, socioeconomic status), specified morbidities, functional ability (Barthel and/or Nottingham Extended Activities of Daily Living), Clinical Frailty Scale (CFS), cognition, and patient-reported outcome measures (dependent on research question). We also propose how additional variables should be measured within an extended dataset. CONCLUSIONS: Our core and extended datasets represent current consensus opinion of academic geriatric medicine clinicians across the UK. We consider the development and further use of these datasets will strengthen collaboration between researchers and academic institutions

    Development of a UK core dataset for geriatric medicine research: : a position statement and results from a Delphi consensus process

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    Funding AS and MW are funded by the Newcastle National Institute for Health (NIHR) Biomedical Research Centre, which also funded the initial meeting of academic clinicians in geriatric medicine during the Delphi process. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NHS, or the Department of Health. Acknowledgements The authors acknowledge the contributions of members of the UK Geriatric Medicine Core Dataset Extended Working Group.Peer reviewedPublisher PD
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