Mapping the light fantastic at Newgrange

THE WORLD HERITAGE PROPERTY of Brú na Bóinne attracts thousands of visitors from Ireland and around the globe, many drawn by the remarkable winter solstice phenomenon, when the rising sun’s rays illuminate the burial chamber. During 2020 it became clear that public health measures to combat the global pandemic were going to preclude visitor access to the chamber of the Great Mound of Newgrange, including during the annual winter solstice celebrations. When the government agencies OPW and NMS discussed how to manage Newgrange and the solstice during the restrictions, Clare Tuffy, Manager of Visitor Services at Brú na Bóinne, suggested that the absence of visitors from the Newgrange chamber would present an opportunity to advance aspects of the Research Framework, established for the World Heritage Property. This identified areas for further study and analysis, specifically to explore, document and better understand aspects of the solar illumination during the solstice. Guided by Dr Frank Prendergast, a multi-disciplinary team devised a research project to record direct sunlight on the floor of the Newgrange chamber over a period of 41 days centred around winter solstice 2020. A summary of the first results of this research to date is reported here, along with some background information on the solar illumination at Newgrange passage tomb

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.Swedish Research Council et al.Manuscrip

Efficacy of a compulsory homework programme for increasing physical activity and improving nutrition in children: A cluster randomised controlled trial

Background: Most physical activity interventions in children focus on the school setting; however, children typically engage in more sedentary activities and spend more time eating when at home. The primary aim of this cluster randomised controlled trial was to investigate the effects of a compulsory, health-related homework programme on physical activity, dietary patterns, and body size in primary school-aged children. Methods: A total of 675 children aged 7-10 years from 16 New Zealand primary schools participated in the Healthy Homework study. Schools were randomised into intervention and control groups (1:1 allocation). Intervention schools implemented an 8-week applied homework and in-class teaching module designed to increase physical activity and improve dietary patterns. Physical activity was the primary outcome measure, and was assessed using two sealed pedometers that monitored school- and home-based activity separately. Secondary outcome measures included screen-based sedentary time and selected dietary patterns assessed via parental proxy questionnaire. In addition, height, weight, and waist circumference were measured to obtain body mass index (BMI) and waist-to-height ratio (WHtR). All measurements were taken at baseline (T0), immediately post-intervention (T1), and 6-months post-intervention (T2). Changes in outcome measures over time were estimated using generalised linear mixed models (GLMMs) that adjusted for fixed (group, age, sex, group x time) and random (subjects nested within schools) effects. Intervention effects were also quantified using GLMMs adjusted for baseline values. Results: Significant intervention effects were observed for weekday physical activity at home (T1 [P < 0.001] and T2 [P = 0.019]), weekend physical activity (T1 [P < 0.001] and T2 [P < 0.001]), BMI (T2 only [P = 0.020]) and fruit consumption (T1 only [P = 0.036]). Additional analyses revealed that the greatest improvements in physical activity occurred in children from the most socioeconomically deprived schools. No consistent effects on sedentary time, WHtR, or other dietary patterns were observed. Conclusions: A compulsory health-related homework programme resulted in substantial and consistent increases in children's physical activity - particularly outside of school and on weekends - with limited effects on body size and fruit consumption. Overall, our findings support the integration of compulsory home-focused strategies for improving health behaviours into primary education curricula. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000590268. Registered 17 April 2018. © 2019 The Author(s)

Inflammation: the driver of poor outcomes among children with severe acute malnutrition?

Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition and underlies at least 10% of all deaths among children younger than 5 years in low-income countries. SAM is a complex, multisystem disease, with physiological perturbations observed in conjunction with the loss of lean mass, including structural and functional changes in many organ systems. Despite the high mortality burden, predominantly due to infections, the underlying pathogenic pathways remain poorly understood. Intestinal and systemic inflammation is heightened in children with SAM. Chronic inflammation and its consequent immunomodulation may explain the increased morbidity and mortality from infections in children with SAM, both during hospitalization and in the longer term after discharge. Recognition of the role of inflammation in SAM is critical in considering new therapeutic targets in this disease, which has not seen a transformational approach to treatment for several decades. This review highlights the central role of inflammation in the wide-ranging pathophysiology of SAM, as well as identifying potential interventions that have biological plausibility based on evidence from other inflammatory syndromes

Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4+ T Cells That Are Functionally Suppressive

The skin provides an important first line of defence and immunological barrier to invasive pathogens, but immune responses must also be regulated to maintain barrier function and ensure tolerance of skin surface commensal organisms. In schistosomiasis-endemic regions, populations can experience repeated percutaneous exposure to schistosome larvae, however little is known about how repeated exposure to pathogens affects immune regulation in the skin. Here, using a murine model of repeated infection with Schistosoma mansoni larvae, we show that the skin infection site becomes rich in regulatory IL-10, whilst in its absence, inflammation, neutrophil recruitment, and local lymphocyte proliferation is increased. Whilst CD4+ T cells are the primary cellular source of regulatory IL-10, they expressed none of the markers conventionally associated with T regulatory (Treg) cells (i.e. FoxP3, Helios, Nrp1, CD223, or CD49b). Nevertheless, these IL-10+ CD4+ T cells in the skin from repeatedly infected mice are functionally suppressive as they reduced proliferation of responsive CD4+ T cells from the skin draining lymph node. Moreover, the skin of infected Rag-/- mice had impaired IL-10 production and increased neutrophil recruitment. Finally, we show that the mechanism behind IL-10 production by CD4+ T cells in the skin is due to a combination of an initial (day 1) response specific to skin commensal bacteria, and then over the following days schistosome-specific CD4+ T cell responses, which together contribute towards limiting inflammation and tissue damage following schistosome infection. We propose CD4+ T cells in the skin that do not express markers of conventional T regulatory cell populations have a significant role in immune regulation after repeated pathogen exposure and speculate that these cells may also help to maintain skin barrier function in the context of repeated percutaneous insult by other skin pathogensy The Wellcome Trust, grant number: 092745/Z/10/Z

Implementation of a hospice community service redesign: Qualitative research identifying lessons learned

Background: The need to improve equity of access to palliative care is well recognized; however, much less is known about how new models of hospice community services can be successfully introduced. Aim: We aimed to capture learning from the implementation experiences of hospice stakeholders during the first 12 months of a hospice community services redesign. Design: Qualitative research using individual semi-structured interviews (n = 38) and follow-up focus groups (n = 8). Methods: Participants were clinical and non-clinical staff, hospice leaders, volunteers, and external stakeholders. Interviews were analysed with framework analysis using Normalisation Process Theory. Focus groups were used to confirm and prioritise recommendations. Results: Implementation is more likely to be successful where hospice personnel are enabled to work together in understanding and adapting to new ways of working. Participants gave examples of being supported to plan activities, to form networks of participation, to pilot new ways of working, and to appraise and improve their work. Receiving feedback on progress is beneficial. Implementation strategies that are tailored to each context could be effective if they engage with hospice stakeholders to ensure that strategic aims are well-understood and that the necessary resources are available. Positive experiences of implementation are more likely where stakeholders understand the changes and can participate in planning. Where necessary, changes to human resources and technology support systems would ideally be adopted prior to making changes to patient-facing services. Conclusion: This study contributes knowledge from a charitable provider of specialist palliative care during the implementation of a hospice community service redesign. We identified opportunities for future improvement, particularly regarding communication, planning, prioritisation, and feedback. Investment of time and reflection during implementation can support the ambition of hospices to become integrated within a place-based system, to improve access to palliative care within the communities they serve. We report key implementation recommendations for organisations considering service redesign

Cardiac rehabilitation to improve health-related quality of life following trans-catheter aortic valve implantation: a randomised controlled feasibility study: RECOVER-TAVI Pilot, ORCA 4, for the Optimal Restoration of Cardiac Activity Group

Objectives: Transcatheter aortic valve implantation (TAVI) is often undertaken in the oldest frailest cohort of patients undergoing cardiac interventions. We plan to investigate the potential benefit of cardiac rehabilitation (CR) in this vulnerable population. Design: We undertook a pilot randomised trial of CR following TAVI to inform the feasibility and design of a future randomised clinical trial (RCT). Participants: We screened patients undergoing TAVI at a single institution between June 2016 and February 2017. Interventions: Participants were randomised post-TAVI to standard of care (control group) or standard of care plus exercise-based CR (intervention group). Outcomes: We assessed recruitment and attrition rates, uptake of CR, and explored changes in 6-min walk test, Nottingham Activities of Daily Living, Fried and Edmonton Frailty scores and Hospital Anxiety and Depression Score, from baseline (30 days post TAVI) to 3 and 6 months post randomisation. We also undertook a parallel study to assess the use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the post-TAVI population. Results: Of 82 patients screened, 52 met the inclusion criteria and 27 were recruited (3 patients/month). In the intervention group, 10/13 (77%) completed the prescribed course of 6 sessions of CR (mean number of sessions attended 7.5, SD 4.25) over 6 weeks. At 6 months, all participants were retained for follow-up. There was apparent improvement in outcome scores at 3 and 6 months in control and CR groups. There were no recorded adverse events associated with the intervention of CR. The KCCQ was well accepted in 38 post-TAVI patients: mean summary score 72.6 (SD 22.6). Conclusions: We have demonstrated the feasibility of recruiting post-TAVI patients into a randomised trial of CR. We will use the findings of this pilot trial to design a fully powered multicentre RCT to inform the provision of CR and support guideline development to optimise health-related quality of life outcomes in this vulnerable population. Retrospectively registered 3rd October 2016 clinicaltrials.gov NCT02921880. Trial registration: Clinicaltrials.Gov identifier NCT0292188

Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature

Defects in cerebrospinal fluid (CSF) flow may contribute to idiopathic scoliosis. However, the mechanisms underlying detection of CSF flow in the central canal of the spinal cord are unknown. Here we demonstrate that CSF flows bidirectionally along the antero-posterior axis in the central canal of zebrafish embryos. In the cfap298tm304 mutant, reduction of cilia motility slows transport posteriorly down the central canal and abolishes spontaneous activity of CSF-contacting neurons (CSF-cNs). Loss of the sensory Pkd2l1 channel nearly abolishes CSF-cN calcium activity and single channel opening. Recording from isolated CSFcNs in vitro, we show that CSF-cNs are mechanosensory and require Pkd2l1 to respond to pressure. Additionally, adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, reminiscent of kyphosis in humans. These results indicate that CSF-cNs are mechanosensory cells whose Pkd2l1-driven spontaneous activity reflects CSF flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to maintenance of natural curvature of the spine

Fostering a Culture of Collaboration for Change:​ TU Dublin’s Engaged Research Network ​

Engagement drives a strong research culture, fostering collaboration, impact, and sustainability. It enables integration by connecting early-career and senior researchers; enhances research outcomes; and creates more opportunities for funding. This creates a more inclusive, diverse, and dynamic research ecosystem. Engaged research is co-created with stakeholders, e.g. communities, industries, and policymakers, to provide tangible outcomes and impact. TU Dublin has established an Engaged Research Network (ERN) to enable knowledge co-creation. The aim is to build its capacity for Engaged Research, with a focus on the UN Sustainable Development Goals. It focuses on connecting and supporting staff and PhD students and developing and sharing resources and experience. Full network meetings are scheduled twice a year, where the members identify priority initiatives to run. Working groups are established and supported to deliver outcomes from these initiatives during the year. There are currently \u3e130 ERN members, with 3 main working groups, which have delivered positive outcomes: o Mentoring programme development (pilot programme underway)o Hackathon/themed networking events development (events on 2 themes have been supported, including a Greenhouse for Engaged Research in Education (GERE) with the Learning, Teaching and Assessment team, and a collaboration with TU Dublin Radiation and Environmental Science Centre on research roundtables with researchers and community partners, on air, soil and water health) o Network podcast series development (Pilot podcast available on Spotify) This ground-up approach to peer learning is effectively building supports for researchers to enhance their confidence and skills in engaged research, through the ERN