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Autobiography of Anne Murray: tells of the Canadian singer's life from her origins in a coal mining town in Nova Scotia to her arrival on the world stage.

As continued COVID-19 disruption looks likely across the world, perhaps until 2021, contingency plans are evolving in case of further disruption in the 2020-2021 academic year. This includes delivering face-to-face programs fully online for at least part of the upcoming academic year for new and continuing cohorts. This temporary pivot will necessitate distance teaching and learning across almost every conceivable pedagogy, from fundamental degrees to professionally accredited ones. Each institution, program, and course will have its own myriad of individualized needs; however, there is a common question that unites us all: how do we provide teaching and assessment to students in a manner that is accessible, fair, equitable, and provides the best learning whilst acknowledging the temporary nature of the pivot? No \"one size fits all\" solution exists, and many of the choices that need to be made will be far from simple; however, this paper provides a starting point and basic principles to facilitate discussions taking place around the globe by balancing what we know from the pedagogy of online learning with the practicalities imposed by this crisis and any future crises.

Pollinators seek high quality nectar and pollen rewards critical for their growth and reproduction. Volatile emissions from inflorescences may signal plant health and floral resource quality to these flower-visiting insects. To understand the relationship between floral volatile emission and pollinator preference in a field setting, we conducted a replicated garden experiment consisting of 18 native perennial species from three different plant families with varying nutritional resource quality. We collected flower-visiting insects and floral volatile emissions over two field seasons, detecting over 60 volatile compounds and over 150 insect species. We collated trait data of visiting insects (bee or non-bee, body size, degree of sociality, nesting behavior, and whether the visitor was non-native) and evaluated interactions between these traits and volatile composition. Among the insect traits, bees and larger visitors had negative associations with sesquiterpenes, while in contrast visitors with complex nesting behaviors and social insects had positive associations. When comparing plant traits with bee traits, bee visitors had negative associations with purple inflorescences and larger insects and social insects both had positive associations with yellow inflorescences. We tested for direct associations between volatile class and insect taxa and found that sesquiterpenes had a strong positive relationship with hoverfly presence. This work demonstrates the complexity of floral volatiles as signals for pollinating insects and how floral scent composition allows individual compounds to act synergistically or antagonistically. These results can help us to better understand pollinator preferences and visitation patterns in the broad context of chemical ecology.

Abrupt dietary changes, as can be common when managing horses, may lead to compositional changes in gut microbiota, which may result in digestive or metabolic disturbances. The aim of this study was to describe and compare the faecal microbiota of ponies abruptly changed from pasture grazing ad libitum to a restricted hay-only diet and vice versa. The experiment consisted of two, 14-day periods. Faecal samples were collected on day 0 and days 1-3,7,14 after abrupt dietary change from grass to hay and from hay to grass. Microbial populations were characterised by sequencing the V3-V4 region of the 16S rRNA gene using the Illumina MiSeq platform, 4,777,315 sequences were obtained from 6 ponies. Further analyses were performed to characterise the microbiome as well as the relative abundance of microbiota present. The results of this study suggest that the faecal microbiota of mature ponies is highly diverse, and the relative abundances of individual taxa change in response to abrupt changes in diet. The faecal microbiota of ponies maintained on a restricted amount of hay-only was similar to that of the ponies fed solely grass ad libitum in terms of richness and phylogenetic diversity; however, it differed significantly in terms of the relative abundances at distinct taxonomic levels. Class Bacilli, order Lactobacillales, family Lactobacillaceae, and genus Lactobacillus were presented in increased relative abundance on day 2 after an abrupt dietary change from hay to grass compared to all other experimental days (P <0.05). Abrupt changes from grass to hay and vice versa affect the faecal microbial community structure; moreover, the order of dietary change appears to have a profound effect in the first few days following the transition. An abrupt dietary change from hay to grass may represent a higher risk for gut disturbances compared to abrupt change from grass to hay.

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea–mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted (Gatmc/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatmc/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatmc/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

ObjectiveTo validate a hypoxic ischaemic encephalopathy (HIE) prediction algorithm to identify infants at risk of HIE immediately after birth using readily available clinical data.DesignSecondary review of electronic health record data of term deliveries from January 2017 to December 2021.SettingA tertiary maternity hospital.PatientsInfants >36 weeks’ gestation with the following clinical variables available: Apgar Score at 1 min and 5 min, postnatal pH, base deficit, and lactate values taken within 1 hour of birthInterventionsPreviously trained open-source logistic regression and random forest (RF) prediction algorithms were used to calculate a probability index (PI) for each infant for the occurrence of HIE.Main outcomeValidation of a machine learning algorithm to identify infants at risk of HIE in the immediate postnatal period.Results1081 had a complete data set available within 1 hour of birth: 76 (6.95%) with HIE and 1005 non-HIE. Of the 76 infants with HIE, 37 were classified as mild, 29 moderate and 10 severe. The best overall accuracy was seen with the RF model. Median (IQR) PI in the HIE group was 0.70 (0.53–0.86) vs 0.05 (0.02–0.15), (p<0.001) in the non-HIE group. The area under the receiver operating characteristics curve for prediction of HIE=0.926 (0.893–0.959, p<0.001). Using a PI cut-off to optimise sensitivity of 0.30, 936 of the 1081 (86.5%) infants were correctly classified.ConclusionIn a large unseen data set an open-source algorithm could identify infants at risk of HIE in the immediate postnatal period. This may aid focused clinical examination, transfer to tertiary care (if necessary) and timely intervention.

Key Points The majority of patients with chronic kidney disease (CKD) incur neurological complications that might improve following renal transplantation Proteinuria, decreased glomerular filtration rate (GFR), and increased cystatin C are risk factors for cerebrovascular disease, which is in turn a risk factor for ongoing kidney dysfunction Stroke is a major complication of CKD in elderly patients undergoing dialysis; conventional ischaemic risk factors, as well as dialysis itself, can contribute to the development of stroke Patients undergoing dialysis often develop delirium after dialysis sessions, as well as chronic dementia, with prominent deficits in executive function and memory that are independent of age Systemic inflammation, oxidative stress, and dysregulation of sodium, potassium, and water channels in acute kidney injury can lead to brain injury, dysfunction, and oedema The kidney and the brain exhibit extensive organ crosstalk due to similarities in their vasculature and shared humoral and non-humoral pathways. In this Review, Claudio Ronco et al . evaluate the effects of chronic kidney disease, end-stage renal disease, and acute kidney injury on cognitive and cerebrovascular function. The authors also highlight the risk factors for cognitive impairment in patients undergoing dialysis. Patients with kidney disease often exhibit multiple organ dysfunction that is caused, in part, by marked connectivity between the kidney and other organs and tissues. Substantial crosstalk occurs between the kidney and the brain, as indicated by the frequent presentation of neurological disorders, such as cerebrovascular disease, cognitive impairment, and neuropathy during the natural history of chronic kidney disease. The underlying pathophysiology of such comorbid neurological disorders in kidney disease is governed by shared anatomic and vasoregulatory systems and humoral and non-humoral bidirectional pathways that affect both the kidney and the brain. During acute kidney injury, the brain and kidney might interact through the amplification of cytokine-induced damage, extravasation of leukocytes, oxidative stress, and dysregulation of sodium, potassium, and water channels. The advent of dialysis and renal transplantation programmes has led to a reduction in the rate of neurological complications associated with uraemia, but a new set of complications have arisen as a consequence of the effects of dialysis on the central nervous system over the short and long term. This Review discusses the clinical complications of acute and chronic renal failure from a neurologic perspective, and highlights current understanding of the underlying pathophysiologies.

Background This project sought to expand patient and public involvement (PPI) practices to the development of research finding dissemination with people aged 55+ years. The project is innovative due to its UK‐wide approach and use of PPI to plan better ways to share findings of health research with older adults, extending PPI beyond research project initiation to support dissemination activities. Objective The aim of this study is to understand how to develop effective public engagement activities with older adults to disseminate findings of health research. We hope to promote greater inclusivity and advance our understanding of this demographic. Methods This project combined three approaches: (i) an online questionnaire to ask what activities older adults enjoy; (ii) online planning workshops seeking public contributors' input in event planning and (iii) community events to share research findings and raise awareness of PPI. Activities were carried out in Cardiff, Belfast, Glasgow and Tewkesbury. Results The planning workshops clarified that in‐person activities and offering options for activities were important. Based on feedback from our contributors, all our events focused around a talk and question and answer session. Other short activities included light exercise and a writing activity. Discussion Our multiphase approach helped us develop informative activities that reflected the questionnaire results and the feedback from the workshops, as we tailored our events to each location. A phased approach allowed both researchers and contributors to gradually deepen their understanding. Conclusion Further awareness raising is needed to develop the role older adults currently hold in health research activities. Working closely with existing communities can help broaden diversity. Patient or Public Contribution Thirty‐three public contributors helped facilitate this project. Two of these also contributed to this article by writing a reflection of their experiences, one of whom also provided feedback for the article.

In a trial comparing 100 mg of aspirin with placebo in nearly 20,000 community-dwelling persons 70 years of age or older in Australia and the United States, aspirin use had no effect on the rate of survival free from dementia or physical disability.

Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1879 were depressed at baseline. Participants were given 100 mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; χ2 (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (–0.7; 95% CI –1.4 to –0.1; χ2 (1) = 4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms.