M-CSF and GM-CSF Regulation of STAT5 Activation and DNA Binding in Myeloid Cell Differentiation is Disrupted in Nonobese Diabetic Mice

Defects in macrophage colony-stimulating factor (M-CSF) signaling disrupt myeloid cell differentiation in nonobese diabetic (NOD) mice, blocking myeloid maturation into tolerogenic antigen-presenting cells (APCs). In the absence of M-CSF signaling, NOD myeloid cells have abnormally high granulocyte macrophage colony-stimulating factor (GM-CSF) expression, and as a result, persistent activation of signal transducer/activator of transcription 5 (STAT5). Persistent STAT5 phosphorylation found in NOD macrophages is not affected by inhibiting GM-CSF. However, STAT5 phosphorylation in NOD bone marrow cells is diminished if GM-CSF signaling is blocked. Moreover, if M-CSF signaling is inhibited, GM-CSF stimulation in vitro can promote STAT5 phosphorylation in nonautoimmune C57BL/6 mouse bone marrow cultures to levels seen in the NOD. These findings suggest that excessive GM-CSF production in the NOD bone marrow may interfere with the temporal sequence of GM-CSF and M-CSF signaling needed to mediate normal STAT5 function in myeloid cell differentiation gene regulation

Homology of Distributive Lattices

We outline the theory of sets with distributive operations: multishelves and multispindles, with examples provided by semi-lattices, lattices and skew lattices. For every such a structure we define multi-term distributive homology and show some of its properties. The main result is a complete formula for the homology of a finite distributive lattice. We also indicate the answer for unital spindles and conjecture the general formula for semi-lattices and some skew lattices. Then we propose a generalization of a lattice as a set with a number of idempotent operations satisfying the absorption law.Comment: 30 pages, 3 tables, 3 figure

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

\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

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

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

Effects of social restrictions on people with dementia and carers during the pre-vaccine phase of the COVID-19 pandemic: experiences of IDEAL cohort participants

Copyright © 2022 The Author(s). This qualitative study was designed to understand the impact of social distancing measures on people with dementia and carers living in the community during a period of ongoing restrictions before the COVID-19 vaccination roll-out in England and Wales. We conducted semi-structured interviews with 11 people with dementia and 10 carers (including 3 dyads) living in the community in England and Wales. Participants were recruited during November and December 2020. We used framework analysis to identify issues and elicit suggestions for potential solutions. We identified three interrelated themes. People with dementia experienced a fear of decline in capabilities or mood and attempted to mitigate this. Carers were aware of changes in the person with dementia and an increase in caring responsibilities and for some, there was a change in the relationship. Subsequently, reduced confidence in capabilities to navigate a new and hostile environment created a cyclical dilemma of returning to ‘normal’ where not returning to usual activities made things worse. People with dementia and carers had feelings of neglect and being alone in their struggle, alongside feeling socially excluded during the pandemic when comparing themselves to others in society, and there was little optimism associated with the upcoming vaccine programme. People found their own solutions to reduce the effects of isolation by keeping busy and socially active and practising skills deemed to help reduce the progression of dementia. This and some limited local public initiatives for the general public facilitated feelings of social inclusion. This study adds understanding to existing evidence about the longer-term experience of social isolation several months into the pandemic highlighting the importance of health and community groups and how services can find ways to support, include and interact with people with dementia and carers during and after social restrictions.‘Identifying and mitigating the individual and dyadic impact of COVID-19 and life under physical distancing on people with dementia and carers (INCLUDE)’ was funded by the Economic and Social Research Council (ESRC) through grant ES/V004964/1. Investigators: Clare, L., Victor, C., Matthews, F., Quinn, C., Hillman, A., Burns, A., Allan, L., Litherland, R., Martyr, A., Collins, R., & Pentecost, C. ESRC is part of UK Research and Innovation (UKRI); ‘Improving the experience of Dementia and Enhancing Active Life: living well with dementia. The IDEAL study’ was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR) through grant ES/L001853/2. Investigators: L. Clare, I.R. Jones, C. Victor, J.V. Hindle, R.W. Jones, M. Knapp, M. Kopelman, R. Litherland, A. Martyr, F.E. Matthews, R.G. Morris, S.M. Nelis, J.A. Pickett, C. Quinn, J. Rusted, J. Thom. ESRC is part of UK Research and Innovation (UKRI). IDEAL data were deposited with the UK data archive in April 2020 and will be available to access from April 2023. Details of how the data can be accessed after that date can be found here: http://reshare.ukdataservice.ac.uk/854293/; ‘Improving the experience of Dementia and Enhancing Active Life: a longitudinal perspective on living well with dementia. The IDEAL-2 study’ is funded by Alzheimer’s Society, grant number 348, AS-PR2-16-001; Investigators: L. Clare, I.R. Jones, C. Victor, C. Ballard, A. Hillman, J.V. Hindle, J. Hughes, R.W. Jones, M. Knapp, R. Litherland, A. Martyr, F.E. Matthews, R.G. Morris, S.M. Nelis, C. Quinn, J. Rusted. L. Clare and L Allan acknowledge support from the NIHR Applied Research Collaboration South-West Peninsula. The views expressed are those of the author(s) and not necessarily those of the ESRC, UKRI, NIHR, the Department of Health and Social Care, the National Health Service, or Alzheimer’s Society. The support of ESRC, NIHR and Alzheimer’s Society is gratefully acknowledged

Evaluating 'living well' with mild-to-moderate dementia: Co-production and validation of the IDEAL My Life Questionnaire

YesWe aimed to co-produce and validate an accessible, evidence-based questionnaire measuring 'living well' with dementia that reflects the experience of people with mild-to-moderate dementia. Nine people with dementia formed a co-production group. An initial series of workshops generated the format of the questionnaire and a longlist of items. Preliminary testing with 53 IDEAL cohort participants yielded a shortlist of items. These were tested with 136 IDEAL cohort participants during a further round of data collection and assessed for reliability and validity. The co-production group contributed to decisions throughout and agreed the final version. An initial list of 230 items was reduced to 41 for initial testing, 12 for full testing, and 10 for the final version. The 10-item version had good internal consistency and test-retest reliability, and a single factor structure. Analyses showed significant large positive correlations with scores on measures of quality of life, well-being, and satisfaction with life, and expected patterns of association including a significant large negative association with depression scores and no association with cognitive test scores. The co-produced My Life Questionnaire is an accessible and valid measure of 'living well' with dementia suitable for use in a range of contexts.This work was supported by the Economic and Social Research Council, National Institute for Health and Care Research (ES/L001853/2), and Alzheimer’s Society (348, AS-PR2-16-001)

Evaluating ‘living well’ with mild-to-moderate dementia: Co-production and validation of the IDEAL My Life Questionnaire

Data availability statement: The My Life Questionnaire is free to use. A printable version can be downloaded from the Living with Dementia Toolkit https://livingwithdementiatoolkit.org.uk/home/how-are-you-feeling-today/ or via this link https://medicine.exeter.ac.uk/reach/publications/. Requests for further information about the IDEAL My Life Questionnaire may be directed to [email protected]. IDEAL cohort data were deposited with the UK Data Archive in April 2020. Details of how to access the data can be found here: https://reshare.ukdataservice.ac.uk/854293/.Copyright © The Author(s) 2023.. Objectives: We aimed to co-produce and validate an accessible, evidence-based questionnaire measuring ‘living well’ with dementia that reflects the experience of people with mild-to-moderate dementia. Methods: Nine people with dementia formed a co-production group. An initial series of workshops generated the format of the questionnaire and a longlist of items. Preliminary testing with 53 IDEAL cohort participants yielded a shortlist of items. These were tested with 136 IDEAL cohort participants during a further round of data collection and assessed for reliability and validity. The co-production group contributed to decisions throughout and agreed the final version. Results: An initial list of 230 items was reduced to 41 for initial testing, 12 for full testing, and 10 for the final version. The 10-item version had good internal consistency and test-retest reliability, and a single factor structure. Analyses showed significant large positive correlations with scores on measures of quality of life, well-being, and satisfaction with life, and expected patterns of association including a significant large negative association with depression scores and no association with cognitive test scores. Conclusions: The co-produced My Life Questionnaire is an accessible and valid measure of ‘living well’ with dementia suitable for use in a range of contexts.Economic and Social Research Council, National Institute for Health and Care Research (ES/L001853/2); Alzheimer's Society (348, AS-PR2-16-001)

Minimal Impact of COVID-19 Pandemic on the Mental Health and Wellbeing of People Living With Dementia: Analysis of Matched Longitudinal Data From the IDEAL Study

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The datasets presented in this article are not readily available because IDEAL data were deposited with the UK data archive in April 2020 and will be available to access from April 2023. Details of how the data can be accessed after that date can be found at: http://reshare.ukdataservice.ac.uk/854293/. INCLUDE data will be archived in connection with the IDEAL dataset in March 2022. Requests to access the datasets should be directed to http://reshare.ukdataservice.ac.uk/854293/ or Linda Clare [email protected]: Research suggests a decline in the mental health and wellbeing of people with dementia (PwD) during the COVID-19 pandemic; however few studies have compared data collected pre-pandemic and during the pandemic. Moreover, none have compared this change with what would be expected due to dementia progression. We explored whether PwD experienced changes in mental health and wellbeing by comparing pre-pandemic and pandemic data, and drew comparisons with another group of PwD questioned on two occasions prior to the pandemic. Methods: Community-dwelling PwD enrolled in the IDEAL programme were split into two groups matched for age group, sex, dementia diagnosis, and time since diagnosis. Although each group was assessed twice, one was assessed prior to and during the pandemic (pandemic group; n = 115) whereas the other was assessed prior to the pandemic (pre-pandemic group; n = 230). PwD completed measures of mood, sense of self, wellbeing, optimism, quality of life, and life satisfaction. Results: Compared to the pre-pandemic group, the pandemic group were less likely to report mood problems, or be pessimistic, but more likely to become dissatisfied with their lives. There were no changes in continuity in sense of self, wellbeing, and quality of life. Discussion: Results suggest the pandemic had little effect on the mental health and wellbeing of PwD, with any changes observed likely to be consistent with expected rates of decline due to dementia. Although personal accounts attest to the challenges experienced, PwD appear to have been resilient to the impact of lockdown and social restrictions during the pandemic.Economic and Social Research Council (ESRC)National Institute for Health Research (NIHR)Alzheimer’s Societ