Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life

Quantifying fenbendazole and its metabolites in self-medicating wild red grouse Lagopus lagopus scoticus using an HPLC–MS–MS approach

On red grouse estates in the UK the nematode parasite Trichostrongylus tenuis is often controlled by application of grit medicated with the anthelmintic fenbendazole (FBZ). To date, assessment of the efficacy has been inhibited by the inability to quantify uptake of FBZ by the birds. We have developed a simple and sensitive HPLC–MS–MS method for detecting and quantifying FBZ and its metabolites from a 300 mg sample of red grouse liver. This method could be used to improve the efficacy of medicated grit treatment by allowing the identification of conditions and application methods that optimize the uptake of FBZ. With the necessary modifications, our method will also be applicable to other wildlife species where self-medication is used for parasite control

Evidence and methods required to evaluate the impact for patients who use social prescribing : a rapid systematic review and qualitative interviews

Background Social prescribing encourages health-care and other professionals to refer patients to a link worker, who will develop a personalised plan to improve the patient’s health and well-being. We explore the feasibility of evaluating the service. Objective The objective was to answer the following research questions. (1) What are the most important evaluation questions that an impact study could investigate? (2) What data are already available at a local or national level and what else would be needed? (3) Are there sites delivering at a large enough scale and in a position to take part in an impact study? (4) How could the known challenges to evaluation (e.g. information governance and identifying a control group) be addressed? Data sources Data sources included MEDLINE ALL (via Ovid), searched from inception to 14 February 2019, and the first 100 hits of a Google (Google Inc., Mountain View, CA, USA) search. Review methods Rapid systematic review – electronic searches up to February 2019. Studies included any study design or outcomes. Screening was conducted by one reviewer; eligibility assessment and data extraction were undertaken by two reviewers. Data were synthesised narratively. Qualitative interviews – data from 25 participants in different regions of England were analysed using a pragmatic framework approach across 12 areas including prior data collection, delivery sites, scale and processes of current service delivery, and known challenges to evaluation. Views of key stakeholders (i.e. patients and academics) were captured. Results Rapid systematic review – 27 out of 124 studies were included. We identified outcomes and highlighted research challenges. Important evaluation questions included identification of the most appropriate (1) outcomes and (2) methods for dealing with heterogeneity. Qualitative interviews – social prescribing programmes are holistic in nature, covering domains such as social isolation and finance. Service provision is heterogeneous. The follow-on services that patients access are often underfunded or short term. Available data – there was significant heterogeneity in data availability, format and follow-up. Data were collected using a range of tools in ad hoc databases across sites. Non-attendance data were frequently not captured. Service users are more deprived and vulnerable than the overall practice population. Feasibility and potential limitations of an evaluation – current data collection is limited in determining the effectiveness of the link worker social prescribing model; therefore, uniform data collection across sites is needed. Standardised outcomes and process measures are required. Cost–utility analysis could provide comparative values for assessment alongside other NHS interventions. Limitations This was a rapid systematic review that did not include a systematic quality assessment of studies. COVID-19 had an impact on the shape of the service. We were not able to examine the potential causal mechanisms in any detail. Conclusions We describe possible future research approaches to determine effectiveness and cost-effectiveness evaluations; all are limited in their application. (1) Evaluation using currently available, routinely collected health-care, costing and outcomes data. (2) Evaluative mixed-methods research to capture the complexity of social prescribing through understanding heterogeneous service delivery across comparative settings. Cost-effectiveness evaluation using routinely available costing and outcomes data to supplement qualitative data. (3) Interventional evaluative research, such as a cluster randomised controlled trial focused on the link worker model. Cost-effectiveness data collected as part of the trial. Future work Mature data are currently not available. There needs to be an agreement across schemes on the key outcomes that need to be measured, harmonisation of data collection, and follow-up referrals (how and when). Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 29. See the NIHR Journals Library website for further project information

Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity

The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no non-invasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc- maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here we show that tumor cell retention of a system xc--specific positron emission tomography radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds. The decrease in [18F]FSPG retention correlated with a depletion of intracellular cystine resulting from increased de novo glutathione biosynthesis, shown through [U-13C6, U-15N2]cystine isotopic tracing. In vivo, treatment with the chemotherapeutic doxorubicin decreased [18F]FSPG tumor uptake in a mouse model of ovarian cancer, coinciding with markers of oxidative stress but preceding tumor shrinkage and decreased glucose utilization. Having already been used in pilot clinical trials, [18F]FSPG PET could be rapidly translated to the clinic as an early redox indicator of tumor response to treatment

What is the best way to evaluate social prescribing? A qualitative feasibility assessment for a national impact evaluation study in England

Objectives Despite significant investment in social prescribing in England over the last decade, we still do not know if it works, or how models of social prescribing fit within wider health and care policy and practice. This study explores current service delivery structures and assesses the feasibility of a national evaluation of the link worker model. Methods Semi-structured interviews were conducted between May and September 2020, with 25 key informants from across social prescribing services in England. Participants included link workers, voluntary, community and social enterprise staff, and those involved in policy and decision-making for social prescribing services. Interview and workshop transcripts were analysed thematically, adopting a framework approach. Results We found differences in how services are provided, including by individual link workers, and between organisations and regions. Standards, referral pathways, reporting, and monitoring structures differ or are lacking in voluntary services as compared to clinical services. People can self-refer to a link worker or be referred by a third party, but the lack of standardised processes generated confusion in both public and professional perceptions of the link worker model. We identified challenges in determining the appropriate outcomes and outcome measures needed to assess the impact of the link worker model. Conclusions The current varied service delivery structures in England poses major challenges for a national impact evaluation. Any future rigorous evaluation needs to be underpinned with national standardised outcomes and process measures which promote uniform data collection

Assessing a potential non-invasive method for viral diagnostic purposes in European squirrels.

Viral infections globally threaten wild and captive mammal populations, with surveillance options limited by a lack of non-invasive diagnostics; especially when infection is asymptomatic in nature. We explored the potential for hair samples collected from red (Sciurus vulgaris) and grey (Sciurus carolinensis) squirrels to provide a means of screening for adenovirus (ADV) and squirrelpox virus (SQPV) using evolving polymerase chain reaction (PCR) assays. An initial pilot study phase utilised samples opportunistically harvested from grey squirrels controlled in Gwynedd, United Kingdom (UK). The screening of 319 grey squirrel carcasses revealed 58% spleen ADV DNA qPCR and 69% SQPV antibody enzyme linked immunosorbent assay (ELISA) positives. We developed new nested ADV and SQPV qPCRs and examined tail hair samples from a sub-set of 80 of these 319 sampled squirrels and these assays amplified ADV and SQPV DNA in a higher proportion of animals than the original qPCR (94% and 21% respectively). Tail hair samples obtained from six Cumbrian red squirrels which had died from squirrelpox disease also revealed 100% SQPV and 50% ADV DNA positive by the nested qPCR assays. These findings indicate enhanced sensitivity for the new platform. The integration of this non-invasive approach in assessing viral infection has wide application in epidemiological studies of wild mammal populations, in particular, during conservation translocations, where asymptomatic infections are of concern

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SNP calls for chromosome 5 from bulked segregant analysis. F1s were generated from crosses between a self-incompatible and a self-compatible parent of Arabidopsis lyrata, sampled from the Great Lakes region of Eastern North America, which were then crossed amongst themselves to create F2s. Pools were created from: 1) 10 individuals that were phenotypically self-incompatible; and 2) 10 individuals that were phenotypically self-compatible. Three lanes of separate runs (two 150 bp and one 100 bp paired-end read run) were sequenced on an Illumina GAII instrument for each pool. The Illumina quality-filtered reads were mapped against the A. lyrata reference genome sequence MN47 (Hu et al. 2011) using GenomeMapper (Schneeberger et al. 2009), allowing for up to 10% mismatches/gaps relative to the read length. All alternative alleles relative to the reference base with a minimum frequency within each pool of 10% and a score of at least 25 were called by SHORE, as described (Ossowski et al. 2008). SNP calls (in genes only) were made using SHORE and compared for the two pools against the MN47 reference and for a reference genome constructed from two self-compatible individuals (AL4). These individuals were created by hybridisation between individuals sampled from the same population used for the self-compatible parent of the pools with the MN47 reference strain. The genomic sequence thus was determined by subtraction from the MN47 reference. The data file shows the SNP calls, % of reads with the variant and read coverage for that position. See readme file for complete details. References Hu TT, Pattyn P, Bakker EG, et al. (2011) The Arabidopsis lyrata genome sequence and the basis of rapid genome size change. Nature Genetics 43, 476-481. doi: 10.1038/ng.807 Ossowski S, Schneeberger K, Clark RM, et al. (2008) Sequencing of natural strains of Arabidopsis thaliana with short reads. Genome Research 18, 2024-2033. 10.1101/gr.080200.108 Schneeberger K, Hagmann J, Ossowski S, et al. (2009) Simultaneous alignment of short reads against multiple genomes. Genome Biology 10, 1-12. 10.1186/gb-2009-10-9-r9

Paternal attractiveness and the effects of differential allocation of parental investment

The differential allocation hypothesis (DAH) predicts that an individual should vary its reproductive investment according to the attractiveness of its mate. A recently revised version of the DAH makes explicit that investment can be positive, i.e. higher for the offspring of attractive males which should be of higher quality, or negative, i.e. higher for offspring of unattractive males, for example compensating for inheriting poor paternal genes. Moreover, investment can be made by the father and the mother. Here, we tested whether experimental manipulation of male attractiveness affected parental investment at different reproductive stages and thus influenced fitness-related traits in offspring. In two aviaries, all male zebra finches, Taeniopygia guttata, were given red leg rings to increase attractiveness and in two aviaries all males received green leg rings to decrease attractiveness. This controlled for assortative mating between treatments. Ring colour was merely an experimental manipulation of male attractiveness, not paternal quality, so we might expect additional investment to elevate offspring quality. Eggs were cross-fostered between and within treatments to allow differentiation of effects of investment in eggs and nestlings. Clutch and brood sizes were standardized. Both positive and negative investment were observed: Eggs from red-ringed fathers had higher yolk to albumen ratios than eggs from green-ringed fathers. Nestlings from eggs laid and incubated by parents in the red-ringed group had higher hatching masses than those in the green-ringed group. Both parents in the green-ringed group fed nestlings more frequently than red-ringed parents. Offspring performance was influenced by the treatment of both foster and biological parents, but combined effects of these different investment patterns on fitness-related traits were ambiguous. Male attractiveness appeared to affect patterns of reproductive investment but not consistently across all forms of reproductive investment suggesting that the costs and benefits of differential allocation vary among individuals and across contexts

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Smoke, curtains and mirrors: the production of race through time and title registration

This article analyses the temporal effects of title registration and their relationship to race. It traces the move away from the retrospection of pre-registry common law conveyancing and toward the dynamic, future-oriented Torrens title registration system. The Torrens system, developed in early colonial Australia, enabled the production of ‘clean’, fresh titles that were independent of their predecessors. Through a process praised by legal commentators for ‘curing’ titles of their pasts, this system produces indefeasible titles behind its distinctive ‘curtain’ and ‘mirror’, which function similarly to magicians’ smoke and mirrors by blocking particular realities from view. In the case of title registries, those realities are particular histories of and relationships with land, which will not be protected by property law and are thus made precarious. Building on interdisciplinary work which theorises time as a social tool, I argue that Torrens title registration produces a temporal order which enables land market coordination by rendering some relationships with land temporary and making others indefeasible. This ordering of relationships with land in turn has consequences for the human subjects who have those relationships, cutting futures short for some and guaranteeing permanence to others. Engaging with Renisa Mawani and other critical race theorists, I argue that the categories produced by Torrens title registration systems materialise as race