Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice

Acknowledgements We would like to thank the Biological Services Facility at the University of Manchester for expert animal husbandry and Karen Davies who helped with the MRI. The Histology Facility equipment that was used in this study was purchased by the University of Manchester Strategic Fund. Special thanks goes to Peter Walker for their help with the histology. Funding information This work was supported by the Kohn Foundation, an Edward Bonham Carter Doctoral Scholarship, an EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine studentship grant (EP/L014904/1), and the Medical Research Council (MR/K501311/1).Peer reviewedPublisher PD

Deep dives: different groups’ experiences of and recovery needs from Covid-19

This national research into Covid-19 was undertaken with a biopsychosocial lens (Engels, 1977), that is to say, exploring the biological, psychological and social factors arising from Covid-19. Some factors could be predicted prior to the research and formed a skeleton analytical framework. This was expanded iteratively as each narrative was explored, with new factors recounted in narratives added to the framework. In this report we take a ‘deep dive’ seeking data pertaining to certain groups of people in order to provide specific insights into the needs of these groups rather than risking the specific disappearing into the general. This is not to treat different people’s needs in isolation, or as discrete. Different demographics and characteristics intersect influencing different experiences of Covid-19. In discussing the responses of people with a single shared characteristic we are not seeking to simplify or segregate, but rather to draw out nuance to further inform recovery efforts. Due to the nature of our data, these deep dives focus in on the experiences of people who were shielding; people with health or mental health conditions and services needed; people with additional needs and their carers; older adults and their carers; people experiencing decreased employment and financial hardship; experiences of learners and volunteers. It was not possible to consider the experiences of minority groups due to low numbers in the data

Decreased Serum Zinc Is An Effect Of Ageing And Not Alzheimer\u27s Disease

We examined the distribution of zinc in the periphery (erythrocytes and serum) in a large, well-characterised cohort, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, in order to determine if there is systemic perturbation in zinc homeostasis in Alzheimer’s disease (AD). We observed an age dependent decrease in serum zinc of approximately 0.4% per year. When correcting for the age dependent decline in serum zinc no significant difference between healthy controls (HC), mildly cognitively impaired (MCI) or AD subjects was observed

From here and now to there and then : practical recommendations for extrapolating cetacean density surface models to novel conditions

Density surface models (DSMs) are clearly established as a method of choice for the analysis of cetacean line transect survey data, and are increasingly used to inform risk assessments in remote marine areas subject to rising anthropogenic impacts (e.g. the high seas). However, despite persistent skepticism about the validity of extrapolated models, more and more DSMs are being applied well beyond the boundaries of the study regions where field sampling originally took place. This leads to potentially uncertain and error-prone model predictions that may mislead on-the-ground management interventions and undermine conservation decision-making. In addition, no consensus currently exists on the best way to define and measure extrapolation when it occurs, leaving users without the tools they require to audit models projected into novel conditions. Consequently, a transparent and consistent protocol for identifying scenarios under which extrapolation may be appropriate (or conversely, ill-advised) is urgently needed to better gauge how models behave outside the boundaries of sample data and to know how much faith can be placed in their outputs. This report aims to address this gap by synthesising recent advances in extrapolation detection, and presenting recommendations for a minimum standard for measuring extrapolation in novel environmental space. Such guidelines are essential to promoting transparency, replicability, and quality control, and will help marine scientists, managers and policy agencies to (i) better interpret density surfaces and their associated uncertainty; (ii) refine model development and selection approaches; and (iii) optimise the allocation of future survey effort by identifying priority knowledge gaps, e.g. by delineating areas where model predictions are the least supported by data. Our review is accompanied by supplementary R code offering a user-friendly framework for quantifying, summarising and visualising various forms of extrapolation in multivariate environmental space a priori (ahead of model fitting). We illustrate its application with case studies designed to revisit previously published predictions of sperm whale (Physeter macrocephalus) and beaked whale (Ziphiidae spp.) densities in the Northwest Atlantic, and evaluate them in light of several extrapolation metrics. Very early in their training, ecologists are given strong warnings against extrapolating, as model predictions made in data-deficient contexts rely heavily on assumptions that may not hold outside the range of sampled conditions. Navigating the ‘uncharted waters’ of extrapolation, however, is critical to scientific progress, and will be best achieved with a clear understanding of the mechanics, benefits, and limitations of extrapolated models.Publisher PD

Rubidium and potassium levels are altered in Alzheimer's disease brain and blood but not in cerebrospinal fluid

Loss of intracellular compartmentalization of potassium is a biochemical feature of Alzheimer's disease indicating a loss of membrane integrity and mitochondrial dysfunction. We examined potassium and rubidium (a biological proxy for potassium) in brain tissue, blood fractions and cerebrospinal fluid from Alzheimer's disease and healthy control subjects to investigate the diagnostic potential of these two metal ions. We found that both potassium and rubidium levels were significantly decreased across all intracellular compartments in the Alzheimer's disease brain. Serum from over 1000 participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), showed minor changes according to disease state. Potassium and rubidium levels in erythrocytes and cerebrospinal fluid were not significantly different according to disease state, and rubidium was slightly decreased in Alzheimer's disease patients compared to healthy controls. Our data provides evidence that contrasts the hypothesized disruption of the blood-brain barrier in Alzheimer's disease, with the systemic decrease in cortical potassium and rubidium levels suggesting influx of ions from the blood is minimal and that the observed changes are more likely indicative of an internal energy crisis within the brain. These findings may be the basis for potential diagnostic imaging studies using radioactive potassium and rubidium tracers

Teacher agency and professional learning communities; what can Learning Rounds in Scotland teach us?

Recently there has been growth in researching teacher agency. Some research has considered the relationship between teacher agency and professional learning. Similarly, there has been growing interest in professional learning communities as resources for professional learning. Connections have been made between professional learning communities and teacher agency, with professional learning communities seen as an affordance for the exercise of teacher agency. However, it has also been argued that there is little detailed evidence of what happens inside professional learning communities or of teacher agency in action. The research reported here focuses on a form of professional learning community from Scotland: Learning Rounds. It uses data from transcripts of post classroom observation conversations to consider the extent to which Learning Rounds provide an affordance for teacher agency and the extent to which that affordance is utilised. This research makes a contribution in three ways: adding to an empirical understanding of what happens in professional learning communities; understanding how teacher agency is (or is not) exercised in practice; considering what factors might affect the utilisation (or otherwise) of affordances for teacher agency. The paper concludes with several recommendations for developing effective professional learning communities as an affordance for teacher agency

Delivering transformative action in paediatric pain: a <i>Lancet Child &amp; Adolescent Health</i> Commission

Every infant, child, and adolescent will experience pain at times throughout their life. Childhood pain ranges from acute to chronic, and includes procedural, disease-related, breakthrough, and other types of pain. Despite its ubiquity, pain is a major challenge for individuals, families, health-care professionals, and societies. As a private mental experience, pain is often hidden and can go undiscussed or ignored. Undertreated, unrecognised, or poorly managed pain in childhood leads to important and long-lasting negative consequences that continue into adulthood, including continued chronic pain, disability, and distress. This undertreatment of pain should not continue, as there are available tools, expertise, and evidence to provide better treatment for childhood pain

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial

Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. Design: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. Results: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation

The impact of Covid-19 pandemic on hospices : a systematic integrated review and synthesis of recommendations for policy and practice

Background: The Covid-19 pandemic resulted in the development of numerous recommendations for practice and policy for specialist palliative care provided by hospices in United Kingdom (UK), as hospices were significantly affected by the pandemic and protections put in place. The aim of this review is to identify and synthesise recommendations or implications for policy and practice that have been generated for adult hospice specialist palliative care during the first 24 months of the Covid-19 pandemic. Methods: AMED, BNI, CINAHL, EMBASE, EMCARE, HMIC, Medline, PsycINFO, PubMed databases were searched for peer-reviewed papers, as well as hand searchers for grey literature. Literature relating to hospices and Covid-19 in the UK were included and a thematic synthesis of recommendations for hospice policy and practice was undertaken. Results: 858 articles were identified with 12 meeting the inclusion criteria. Fifty-eight recommendations or implications were identified: 31 for policy, 27 for practice, and 10 covering both. Recommendations were organised under ten themes. There were several recommendations seeking to secure hospice resources to mitigate the short-term impact of the pandemic, as well as those focused on longer-term implications such as core funding. The impact of the pandemic on the quality of hospice care was the focus for numerous recommendations around improving integration of hospice care in the community, provision of bereavement support and better use of Advance Care Plans (ACP). However, there were significant gaps related to carer visitation in hospices, inequities of palliative care, or hospice-at-home services. Conclusion: The Covid-19 pandemic and protections exposed several ongoing policy and practice needs, especially around hospice resources, while generating novel issues for hospices to address. Significant policy gaps remain to be addressed to mitigate the impact of the pandemic on the quality of hospice specialist palliative care

UK consensus guidelines for the delivery of unexpected news in obstetric ultrasound: The ASCKS framework

Background: Studies indicate there is a need to improve the delivery of unexpected news via obstetric ultrasound, but there have been few advances in this area. One factor preventing improvement has been a lack of consensus regarding the appropriate phrases and behaviours which sonographers and ultrasound practitioners should use in these situations. Aims: To develop consensus guidelines for unexpected news delivery in Early Pregnancy Unit and Fetal Anomaly Screening Programme NHS settings. Methods: A workshop was conducted to identify priorities and reach consensus on areas of contention. Contributors included interdisciplinary healthcare professionals, policy experts, representatives from third-sector organisations, lay experts and academic researchers (n = 28). Written and verbal feedback was used to draft initial guidance which was then circulated amongst the wider writing group (n = 39). Revisions were undertaken until consensus was reached. Results: Consensus guidelines were developed outlining the behaviours and phrases which should be used during scans where unexpected findings are identified. Specific recommendations included that: honest and clear communication should be prioritised, even with uncertain findings; technical terms should be used, but these should be written down together with their lay interpretations; unless expectant parents use other terminology (e.g. ‘foetus’), the term ‘baby’ should be used as a default, even in early pregnancy; at the initial news disclosure, communication should focus on information provision. Expectant parents should not be asked to make decisions during the scan. Conclusions: These recommendations can be used to develop and improve news delivery interventions in obstetric ultrasound settings. The full guidelines can be accessed online as supplemental material and at https://doi.org/10.5518/100/24