Sperm blocking is not a male adaptation to sperm competition in a parasitoid wasp

This work was supported by a NERC Doctoral Training Grant studentship to RAB. Data archived in Dryad Digital Repository at doi:10.5061/dryad.t0877The extent to which sperm or ejaculate-derived products from different males interact during sperm competition—from kamikaze sperm to sperm incapacitation—remains controversial. Repeated matings in the parasitoid wasp Nasonia vitripennis lead to a short-term reduction of efficient sperm use by females, which is crucial for a haplodiploid organism when needing to allocate sex adaptively (i.e. by fertilizing eggs to produce daughters). Repeated matings by females in this species, therefore, constrain sex allocation through this “sperm-blocking” effect, eliciting a cost to polyandry. Here, we explore the causes and consequences of sperm blocking and test the hypothesis that it is an ejaculate-related trait associated with sperm competition. First, we show that sperm blocking, which leads to an overproduction of sons, is not correlated with success in either offensive or defensive roles in sperm competition. Then, we show that the extent of sperm blocking is not affected by self–self or kin–kin ejaculate interactions when compared to self vs nonself or kin versus nonkin sperm competition. Our results suggest that sperm blocking is not a sperm competition adaptation, but is instead associated with the mechanics of processing sperm in this species, which are likely shaped by selection on female reproductive morphology for adaptive sex allocation.PostprintPeer reviewe

Identifying older adults with frailty approaching end-of-life: A systematic review

From SAGE Publishing via Jisc Publications RouterHistory: epub 2021-09-14Publication status: PublishedFunder: national institute for health research; FundRef: https://doi.org/10.13039/501100000272; Grant(s): PR-PRU-1217-21502Background:: People with frailty may have specific needs for end-of-life care, but there is no consensus on how to identify these people in a timely way, or whether they will benefit from intervention. Aim:: To synthesise evidence on identification of older people with frailty approaching end-of-life, and whether associated intervention improves outcomes. Design:: Systematic review (PROSPERO: CRD42020462624). Data sources:: Six databases were searched, with no date restrictions, for articles reporting prognostic or intervention studies. Key inclusion criteria were adults aged 65 and over, identified as frail via an established measure. End-of-life was defined as the final 12 months. Key exclusion criteria were proxy definitions of frailty, or studies involving people with cancer, even if also frail. Results:: Three articles met the inclusion criteria. Strongest evidence came from one study in English primary care, which showed distinct trajectories in electronic Frailty Index scores in the last 12 months of life, associated with increased risk of death. We found no studies evaluating established clinical tools (e.g. Gold Standards Framework) with existing frail populations. We found no intervention studies; the literature on advance care planning with people with frailty has relied on proxy definitions of frailty. Conclusion:: Clear implications for policy and practice are hindered by the lack of studies using an established approach to assessing frailty. Future end-of-life research needs to use explicit approaches to the measurement and reporting of frailty, and address the evidence gap on interventions. A focus on models of care that incorporate a palliative approach is essential

Food Intakes by Preschool Children in Flanders Compared with Dietary Guidelines

The objective of this study was to compare food group intakes among preschool children with food-based dietary guidelines (FBDG) and to determine the proportion of children meeting these guidelines. Food consumption of preschool children (2.5–6.5 years) living in Flanders (Belgium) were assessed in a cross-sectional study, using proxy reported 3d estimated dietary records (EDR) (n 696). Statistical modelling was used to account for within-individual variation in the 3d EDR. Mean daily intakes of most food groups (beverages, vegetables, fruit and milk) were below the minimum recommendations. Only ‘grains and potatoes’ and ‘meat products’ were in line with the recommendations and ‘bread and cereals’ showed borderline intakes. Mean intakes of energy-dense and low-nutritious foods, which are discouraged within a healthy diet (like snacks and sugared drinks), were high. Furthermore, the percentage of children complying with the different food-based dietary guidelines was for most food groups extremely low (ranging from approximately 4% for fluid and vegetable intakes up to 99% for potato intakes). Boys had in general higher mean intakes of the recommended food groups. In conclusion, preschool children in Flanders follow eating patterns that do not meet Flemish FBDG. Although the impact of these eating habits on preschooler’s current and future health should be further investigated, it is clear that nutrition education and intervention are needed among preschool children and their parents in Flanders

Rapid systematic review of systematic reviews : what befriending, social support and low intensity psychosocial interventions, delivered remotely, may reduce social isolation and loneliness among older adults and how? [version 2; peer review: 2 approved with reservations]

BACKGROUND: During the COVID-19 pandemic ‘social distancing’ has highlighted the need to minimise loneliness and isolation among older adults (aged 50+). We wanted to know what remotely delivered befriending, social support and low intensity psychosocial interventions may help to alleviate social isolation and loneliness and how they work. METHODS: We followed a systematic ‘review of reviews’ approach. Searches of 11 databases from the fields of health, social care, psychology and social science were undertaken during April 2020. Reviews meeting our PICOS criteria were included if they focussed on the evaluation of remote interventions to reduce levels of social isolation or loneliness in adults aged 50+ and were critically appraised using AMSTAR2. Narrative synthesis was used at a review and study level to develop a typology of intervention types and their effectiveness. Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) were used at a study level to explore the characteristics of successful interventions. RESULTS: We synthesised evidence from five systematic reviews and 18 primary studies. Remote befriending, social support and low intensity psychosocial interventions took the form of: (i) supported video-communication; (ii) online discussion groups and forums; (iii) telephone befriending; (iv) social networking sites; and (v) multi-tool interventions. The majority of studies utilised the first two approaches, and were generally regarded positively by older adults, although with mixed evidence around effectiveness. Focussing on processes and mechanisms, using ICA and QCA, we found that the interventions that were most successful in improving social support: (i) enabled participants to speak freely and to form close relationships; (ii) ensured participants have shared experiences/characteristics; (iii) included some form of pastoral guidance. CONCLUSIONS: The findings highlight a set of intervention processes that should be incorporated into interventions, although they do not lead us to recommend specific modes of support, due to the heterogeneity of interventions

Population-based interventions for preventing falls and fall-related injuries in older people.

Around one-third of older adults aged 65 years or older who live in the community fall each year. Interventions to prevent falls can be designed to target the whole community, rather than selected individuals. These population-level interventions may be facilitated by different healthcare, social care, and community-level agencies. They aim to tackle the determinants that lead to risk of falling in older people, and include components such as community-wide polices for vitamin D supplementation for older adults, reducing fall hazards in the community or people's homes, or providing public health information or implementation of public health programmes that reduce fall risk (e.g. low-cost or free gym membership for older adults to encourage increased physical activity). To review and synthesise the current evidence on the effects of population-based interventions for preventing falls and fall-related injuries in older people. We defined population-based interventions as community-wide initiatives to change the underlying societal, cultural, or environmental conditions increasing the risk of falling. We searched CENTRAL, MEDLINE, Embase, three other databases, and two trials registers in December 2020, and conducted a top-up search of CENTRAL, MEDLINE, and Embase in January 2023. We included randomised controlled trials (RCTs), cluster RCTs, trials with stepped-wedge designs, and controlled non-randomised studies evaluating population-level interventions for preventing falls and fall-related injuries in adults ≥ 60 years of age. Population-based interventions target entire communities. We excluded studies only targeting people at high risk of falling or with specific comorbidities, or residents living in institutionalised settings. We used standard methodological procedures expected by Cochrane, and used GRADE to assess the certainty of the evidence. We prioritised seven outcomes: rate of falls, number of fallers, number of people experiencing one or more fall-related injuries, number of people experiencing one or more fall-related fracture, number of people requiring hospital admission for one or more falls, adverse events, and economic analysis of interventions. Other outcomes of interest were: number of people experiencing one or more falls requiring medical attention, health-related quality of life, fall-related mortality, and concerns about falling. We included nine studies: two cluster RCTs and seven non-randomised trials (of which five were controlled before-and-after studies (CBAs), and two were controlled interrupted time series (CITS)). The numbers of older adults in intervention and control regions ranged from 1200 to 137,000 older residents in seven studies. The other two studies reported only total population size rather than numbers of older adults (67,300 and 172,500 residents). Most studies used hospital record systems to collect outcome data, but three only used questionnaire data in a random sample of residents; one study used both methods of data collection. The studies lasted between 14 months and eight years. We used Prevention of Falls Network Europe (ProFaNE) taxonomy to classify the types of interventions. All studies evaluated multicomponent falls prevention interventions. One study (n = 4542) also included a medication and nutrition intervention. We did not pool data owing to lack of consistency in study designs. Medication or nutrition Older people in the intervention area were offered free-of-charge daily supplements of calcium carbonate and vitamin D . Although female residents exposed to this falls prevention programme had fewer fall-related hospital admissions (with no evidence of a difference for male residents) compared to a control area, we were unsure of this finding because the certainty of evidence was very low. This cluster RCT included high and unclear risks of bias in several domains, and we could not determine levels of imprecision in the effect estimate reported by study authors. Because this evidence is of very low certainty, we have not included quantitative results here. This study reported none of our other review outcomes. Multicomponent interventions Types of interventions included components of exercise, environment modification (home; community; public spaces), staff training, and knowledge and education. Studies included some or all of these components in their programme design. The effectiveness of multicomponent falls prevention interventions for all reported outcomes is uncertain. The two cluster RCTs included high or unclear risk of bias, and we had no reasons to upgrade the certainty of evidence from the non-randomised trial designs (which started as low-certainty evidence). We also noted possible imprecision in some effect estimates and inconsistent findings between studies. Given the very low-certainty evidence for all outcomes, we have not reported quantitative findings here. One cluster RCT reported lower rates of falls in the intervention area than the control area, with fewer people in the intervention area having one or more falls and fall-related injuries, but with little or no difference in the number of people having one or more fall-related fractures. In another cluster RCT (a multi-arm study), study authors reported no evidence of a difference in the number of female or male residents with falls leading to hospital admission after either a multicomponent intervention ("environmental and health programme") or a combination of this programme and the calcium and vitamin D programme (above). One CBA reported no difference in rate of falls between intervention and control group areas, and another CBA reported no difference in rate of falls inside or outside the home. Two CBAs found no evidence of a difference in the number of fallers, and another CBA found no evidence of a difference in fall-related injuries. One CITS found no evidence of a difference in the number of people having one or more fall-related fractures. No studies reported adverse events. Given the very low-certainty evidence, we are unsure whether population-based multicomponent or nutrition and medication interventions are effective at reducing falls and fall-related injuries in older adults. Methodologically robust cluster RCTs with sufficiently large communities and numbers of clusters are needed. Establishing a rate of sampling for population-based studies would help in determining the size of communities to include. Interventions should be described in detail to allow investigation of effectiveness of individual components of multicomponent interventions; using the ProFaNE taxonomy for this would improve consistency between studies. [Abstract copyright: Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.

A peer-volunteer led active ageing programme to prevent decline in physical function in older people at risk of mobility disability (Active, Connected, Engaged [ACE]): study protocol for a randomised controlled trial

Background: The Active Connected Engaged [ACE] study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial [RCT] with an internal pilot phase. The ACE study incorporates a multi-level mixed methods process evaluation including a systems mapping approach and an economic evaluation. ACE aims to test the effectiveness and cost-effectiveness of a peer-volunteer led active ageing intervention designed to support older adults at risk of mobility disability to become more physically and socially active within their communities and to reduce or reverse, the progression of functional limitations associated with ageing. Methods/design: Community-dwelling, older adults aged 65 years and older (n = 515), at risk of mobility disability due to reduced lower limb physical functioning (Short Physical Performance Battery (SPPB) score of 4–9 inclusive) will be recruited. Participants will be randomised to receive either a minimal control intervention or ACE, a 6-month programme underpinned by behaviour change theory, whereby peer volunteers are paired with participants and offer them individually tailored support to engage them in local physical and social activities to improve lower limb mobility and increase their physical activity. Outcome data will be collected at baseline, 6, 12 and 18 months. The primary outcome analysis (difference in SPPB score at 18 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. Discussion: ACE is the largest, pragmatic, community-based randomised controlled trial in the UK to target this high-risk segment of the older population by mobilising community resources (peer volunteers). A programme that can successfully engage this population in sufficient activity to improve strength, coordination, balance and social connections would have a major impact on sustaining health and independence. ACE is also the first study of its kind to conduct a full economic and comprehensive process evaluation of this type of community-based intervention. If effective and cost-effective, the ACE intervention has strong potential to be implemented widely in the UK and elsewhere. Trial registration: ISRCTN, ISRCTN17660493. Registered on 30 September 2021. Trial Sponsor: University of Birmingham, Contact: Dr Birgit Whitman, Head of Research Governance and Integrity; Email: [email protected]. Protocol Version 5 22/07/22

Protocol for the PreventIT feasibility randomised controlled trial of a lifestyle-integrated exercise intervention in young older adults

Introduction The European population is rapidly ageing. In order to handle substantial future challenges in the healthcare system, we need to shift focus from treatment towards health promotion. The PreventIT project has adapted the Lifestyle-integrated Exercise (LiFE) programme and developed an intervention for healthy young older adults at risk of accelerated functional decline. The intervention targets balance, muscle strength and physical activity, and is delivered either via a smartphone application (enhanced LiFE, eLiFE) or by use of paper manuals (adapted LiFE, aLiFE). Methods and analysis The PreventIT study is a multicentre, three-armed feasibility randomised controlled trial, comparing eLiFE and aLiFE against a control group that receives international guidelines of physical activity. It is performed in three European cities in Norway, Germany, and The Netherlands. The primary objective is to assess the feasibility and usability of the interventions, and to assess changes in daily life function as measured by the Late-Life Function and Disability Instrument scale and a physical behaviour complexity metric. Participants are assessed at baseline, after the 6 months intervention period and at 1 year after randomisation. Men and women between 61 and 70 years of age are randomly drawn from regional registries and respondents screened for risk of functional decline to recruit and randomise 180 participants (60 participants per study arm). Ethics and dissemination Ethical approval was received at all three trial sites. Baseline results are intended to be published by late 2018, with final study findings expected in early 2019. Subgroup and further in-depth analyses will subsequently be published. Trial registration number NCT03065088; Pre-results

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes