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[This corrects the article DOI: 10.1371/journal.ppat.1011461.].

Fundamental motor skills (FMS) are the cornerstone of a child’s motor development, but concerns remain on the current level of FMS competencies, and intervention is required. This evaluation investigated if a targeted Early Years FMS intervention, delivered by a specialist physical education (PE) provider, improved the FMS of 4–5-year-old children across multiple sites. Methods: The Early Years FMS intervention ran for 18 weeks, 1 h/week, using a standardised programme of activities to develop FMS competencies across 219 children from 15 schools in the Midlands, UK. An adapted assessment was employed as a measure of FMS, assessing locomotor, object control, and stability skills at weeks 1, 9, and 18. The FMS were each rated as green = competent, amber = working towards, or red = not meeting the standards of the skill. A description of key programme implementation characteristics was described. Findings: Statistically significant increases in FMS competencies were achieved for 80% of participants at 18 weeks. Key implementation characteristics for the intervention included consistent staffing, a standardised programme, and a variety of pedagogical approaches delivered by specialist PE staff. Conclusion: This evaluation provided important insights into the effectiveness and implementation of the Early Years FMS intervention to improve FMS competencies in children aged 4–5 years.

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell-derived cytokines initiating type 2 inflammation. During inflammation, ILC2 numbers are increased in the lung. However, the mechanisms controlling ILC2 trafficking and motility within inflamed lungs remain unclear and are crucial for understanding ILC2 function in pulmonary immunity. Using several approaches, including lung intravital microscopy, we demonstrate that pulmonary ILC2s are highly dynamic, exhibit amoeboid-like movement, and aggregate in the lung peribronchial and perivascular spaces. They express distinct chemokine receptors, including CCR8, and actively home to CCL8 deposits located around the airway epithelium. Within lung tissue, ILC2s were particularly motile in extracellular matrix-enriched regions. We show that collagen-I drives ILC2 to markedly change their morphology by remodeling their actin cytoskeleton to promote environmental exploration critical for regulating eosinophilic inflammation. Our study provides previously unappreciated insights into ILC2 migratory patterns during inflammation and highlights the importance of environmental guidance cues in the lung in controlling ILC2 dynamics.

Integrins come in subtypes that bind distinct ligands. This work reveals and quantifies subtype-specific mechanical force transmission and assembly of cytoskeleton architectures.

The ecological state of the Persian or Arabian Gulf (hereafter ‘Gulf') is in sharp decline. Calls for comprehensive ecosystem-based management approaches and transboundary conservation have gone largely unanswered, despite mounting marine threats made worse by climate change. The region's long-standing political tensions add additional complexity, especially now as some Gulf countries will soon adopt ambitious goals to protect their marine environments as part of new global environmental commitments. The recent interest in global commitments comes at a time when diplomatic relations among all Gulf countries are improving. There is a window of opportunity for Gulf countries to meet global marine biodiversity conservation commitments, but only if scientists engage in peer-to-peer diplomacy to build trust, share knowledge and strategize marine conservation options across boundaries. The Gulf region needs more ocean diplomacy and coordination; just as critically, it needs actors at its science-policy interface to find better ways of adapting cooperative models to fit its unique marine environment, political context and culture. We propose a practical agenda for scientist-led diplomacy in the short term and lines of research from which to draw (e.g. co-production, knowledge exchange) to better design future science diplomacy practices and processes suited to the Gulf's setting.

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.

Abstract Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of C. burnetii infection in livestock; and the first report of Neospora caninum, Toxoplasma gondii, and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions.

Family scholarship has documented negative associations between ambivalence and well-being in the context of parent-adult child relationships. As sibling ties remain salient throughout later life, ambivalence experienced in sibling relationships might also be related to older adult well-being. The purpose of this study was to examine the associations between sibling ambivalence and both psychological and physical well-being of older adults, as well as differences in these links by sibling gender composition. Data came from 702 older adults (392 women) who were 64.58 years old on average (SD = 4.51). Structural equation modeling using FIML revealed that participants who felt more ambivalence toward their siblings reported poorer psychological well-being. However, a multiple group analysis showed that this association was only significant for brother-brother pairs. Findings suggest the need to further investigate the implication of sibling ambivalence for psychological well-being in later life, especially for brothers. [ABSTRACT FROM AUTHOR]

One of the most surprising and important findings of the first human landings on the Moon was the discovery of a very fine layer of lunar dust covering the entire surface of Moon along with the negative impacts of this dust on the well-being and operational effectiveness of the astronauts, their equipment, and instrumentation. The United States is now planning for human missions to Mars, a planet where dust can also be expected to be ubiquitous for many or most landing sites. For these missions, the design and operations of key hardware systems must take this dust into account, especially when related to crew health and safety. Improved understanding of Martian dust characteristics can inform its potential to also perform transport of microorganisms, both those inadvertently brought to Mars by the astronauts, or, if Martian microorganisms exist, the potential for their inadvertent return to Earth with the astronauts. Careful planning and design are needed to assure that future missions do not violate the United Nations Outer Space Treaty (1967) signed by all spacefaring nations. In this paper, we review the impact of lunar dust on the Apollo missions and identify several questions about dust in the atmosphere of Mars that may be answered by the curated samples that would be returned by the planned Mars Sample Return (MSR) Campaign. These answers would not only provide an opportunity to better understand the history of Mars but could also reduce uncertainty in charting the future of humanity's exploration of the planet. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the utility of ultrasound (US) imaging for diagnosis of abnormal tracheal morphology, such as tracheal cartilaginous sleeves (TCS), in patients with syndromic craniosynostosis (SC). Study Design: Age‐matched cohort study. Setting: Tertiary pediatric hospital. Methods: Two age‐matched cohorts were identified: patients with SC and known TCS based upon airway endoscopy and normal controls without tracheal pathology. Enrolled patients underwent awake US of the neck which were randomized and reviewed by blinded pediatric radiologists and rated on presence or absence of normal tracheal cartilage morphology and visualization or nonvisualization of a tracheostomy tube. Fisher's exact test was used to assess pooled data. Fleiss' Kappa (κ) was calculated to assess inter‐rater reliability. Results: Ten patients were included in each cohort. Control patients were gender and age‐matched to TCS patients with a mean difference of 3.7 months (±3.9 months). Across all raters, cartilage type was correctly identified in 93% (95% confidence interval [CI]: 84%‐98%) and tracheostomy visualization in 97% (95% CI: 89%‐99%). The sensitivity and specificity for detection of abnormal cartilage pathology was 87% and 100%, respectively. Inter‐rater reliability for cartilage assessment was κ = 0.88 (95% CI: 0.67‐1.00, P <.05) and 0.83 (95% CI: 0.58‐1.00, P <.05) for tracheostomy presence. Conclusion: This study demonstrated that tracheal US is a feasible, accurate screening tool for TCS, and can be successfully performed non‐sedated in patients up to 18 years of age, both with and without tracheostomy tubes in place. [ABSTRACT FROM AUTHOR]

Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children. In this study, we developed an in silico model describing the pulmonary immune response to a common allergen, house dust mite, to investigate its downstream impact on the pathophysiology of asthma, including airway eosinophilic inflammation, remodelling, and lung function. We hypothesised that altered epithelial function following allergen exposure determines the onset of airway remodelling and abnormal lung function, which are irreversible with current asthma therapies. We calibrated the in silico model using age appropriate in vivo data from neonatal and adult mice. We validated the in silico model using in vivo data from mice on the effects of current treatment strategies. The in silico model recapitulates experimental observations and provides an interpretable in silico tool to assess airway pathology and the underlying immune responses upon allergen exposure. The in silico model simulations predict the extent of bronchial epithelial barrier damage observed when allergen sensitisation occurs and demonstrate that epithelial barrier damage and impaired immune maturation are critical determinants of reduced lung function and asthma development. The in silico model demonstrates that both epithelial barrier repair and immune maturation are potential targets for therapeutic intervention to achieve successful asthma prevention. [ABSTRACT FROM AUTHOR]

Objectives To develop a reproducible, reliable clinical index of alveolar bone grafting (ABG) outcome based on the eruption position of the cleft canine tooth and determine the association between eruption position and radiographic outcome at 6 months post-grafting. Methods Children with complete, non-syndromic, unilateral/bilateral cleft lip and palate in the West of Scotland were identified. Post-ABG radiographic outcome (Kindelan index) and canine eruption position in children with a cleft of the alveolus who had undergone ABG were documented. A Kindelan score was assigned to the 6-month post-bone-graft radiograph. Following canine tooth eruption, four-point clinical index scale (CIS) scores were assigned to maxillary occlusal images taken prior to commencement of definitive orthodontics; 1—canine eruption in alveolar crest, 2—canine eruption buccal to alveolar crest, 3—canine eruption palatal to alveolar crest, and 4—canine impaction. Intra and inter-rater reliability was assessed using Cohen and Fleiss kappa's, respectively. Duration of orthodontics treatment, number of orthodontic clinic visits, and clinical management of the cleft site space were noted. Results Eighty-three patients representing 98 bone graft sites were identified. CIS scoring intra- and inter-rater reliability was 0.69–0.99 and 0.63–0.75, respectively. CIS score was associated with reduced visits (P  = .015), months in orthodontics (P  = .009), and likelihood of space closure (P  = .006). Limitations This is a retrospective study with small numbers but is comparative to other similar studies in the literature. Conclusions The CIS presented appears to be a reliable index of ABG outcome. It also demonstrates an association with the burden of orthodontic care post-cleft alveolar bone graft. [ABSTRACT FROM AUTHOR]

Infections caused by acute respiratory viruses induce a systemic innate immune response, which can be measured by the increased levels of expression of inflammatory genes in immune cells. There is growing evidence that these acute viral infections, alongside transient transcriptomic responses, induce epigenetic remodeling as part of the immune response, such as DNA methylation and histone modifications, which might persist after the infection is cleared. In this article, we first review the primary mechanisms of epigenetic remodeling in the context of innate immunity and inflammation, which are crucial for the regulation of the immune response to viral infections. Next, we delve into the existing knowledge concerning the impact of respiratory virus infections on the epigenome, focusing on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Influenza A Virus (IAV), and Respiratory Syncytial Virus (RSV). Finally, we offer perspectives on the potential consequences of virus-induced epigenetic remodeling and open questions in the field that are currently under investigation.

Incidence and mortality rates from cervical cancer are two and four times higher, respectively, for Aboriginal and Torres Strait Islander women compared with non?Indigenous women, despite a nationally organised cervical [...], : Objective: This study aimed to describe Aboriginal and Torres Strait Islander women&apos;s views of self?collection introduced in the renewed National Cervical Screening Program. Methods: A total of 79 Aboriginal and/or Torres Strait Islander women (50 screened in previous five years, 29 under?screened) from five clinics across three Australian states/territories participated. Topics discussed were perceptions of self?collection, the instruction card and suggestions for implementing self?collection. We employed yarning (a qualitative method), which established relationships and trust between participants and researchers to facilitate culturally safe conversations. Transcripts were analysed thematically. Results: Most women were unaware of self?collection before the yarn but found it to be an acceptable way to participate in cervical screening. Women perceived self?collection would be convenient, provide a sense of control over the screening experience, and maintain privacy and comfort. The instructions were perceived to be simple and easy to follow. Women had concerns about collecting the sample correctly and the accuracy of the sample (compared to clinician?collected samples). Conclusions: Self?collection is acceptable to Aboriginal and Torres Strait Islander women. Implications for public health: Given the inequitable burden of cervical cancer experienced by Aboriginal and Torres Strait Islander women, self?collection is likely to significantly improve participation and ultimately improve cervical cancer outcomes.

This study examined proficiency levels in fundamental motor skills (FMS) in children within Key Stage 1 and 2 of the English school system. Four hundred and ninety-two children aged 6-9 Years old (245 boys, 247 girls) from school Years Two (n = 130), Three (n = 154) and Four (n = 208) participated in this study. FMS for the run, jump, throw and catch were assessed using the Test of Gross Motor Development -- 2. The proportion of children who achieved mastery or near mastery of the skills was determined. For the whole sample, 18.5% (n = 91) did not achieve mastery in any of the four skills. A similar proportion (18.7%, n = 92) achieved mastery in all four of the FMS examined in this study. The proportion of children achieving mastery of all four skills was lower for Year Two children (0%) compared to children in years Three (24%) and Four (25%). More boys (25.7%) achieved mastery in all four of the FMS compared to girls (11.7%). Individual behavioural components in skill performance were also examined. The results of the present study highlight that less than one-fifth of children aged 6-9 years old have mastered the four key FMS identified by the physical education (PE) curriculum despite having the developmental potential to become fundamentally competent by six years of age. Fostering positive trajectories of FMS development presents a challenge for PE specialists given the association between FMS mastery in childhood and physical activity, weight status and health.

Background: Many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of ‘doctor-diagnosed asthma’, thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes. Methods: We conducted a novel multivariate GWAS meta-analysis of wheezing phenotypes jointly derived using unbiased analysis of data collected from birth to 18 years in 9568 individuals from five UK birth cohorts. Results: Forty-four independent SNPs were associated with early-onset persistent, 25 with pre-school remitting, 33 with mid-childhood remitting, and 32 with late-onset wheeze. We identified a novel locus on chr9q21.13 (close to annexin 1 [ANXA1], p

Abstract Glaciers and ice caps (GICs) are important contributors of meltwater runoff and to global sea level rise. However, knowledge of GIC mass changes is largely restricted to the last few decades. Here we show the extent of 5327 Greenland GICs during Little Ice Age (LIA) termination (1900) and reveal that they have fragmented into 5467 glaciers in 2001, losing at least 587 km3 from their ablation areas, equating to 499 Gt at a rate of 4.34 Gt yr−1. We estimate that the long‐term mean mass balance in glacier ablation areas has been at least −0.18 to −0.22 m w.e. yr−1 and note the rate between 2000 and 2019 has been three times that. Glaciers with ice‐marginal lakes formed since the LIA termination have had the fastest changing mass balance. Considerable spatial variability in glacier changes suggest compounding regional and local factors present challenges for understanding glacier evolution.

Recruitment of poliovirus (PV) RNA to the human ribosome requires the coordinated interaction of the viral internal ribosome entry site (IRES) and several host cellular initiation factors and IRES trans-acting factors (ITAFs). Attenuated PV Sabin strains contain point mutations in the PV IRES domain V (dV) that inhibit viral translation. Remarkably, attenuation is most apparent in cells of the central nervous system, but the molecular basis to explain this is poorly understood. The dV contains binding sites for eukaryotic initiation factor 4G (eIF4G) and polypyrimidine tract-binding protein (PTB). Impaired binding of these proteins to the mutant IRESs has been observed, but these effects have not been quantitated. We used a fluorescence anisotropy assay to reveal that the Sabin mutants reduce the equilibrium dissociation constants of eIF4G and PTB to the PV IRES by up to 6-fold. Using the most inhibitory Sabin 3 mutant, we used a real-time fluorescence helicase assay to show that the apparent affinity of an active eIF4G/4A/4B helicase complex for the IRES is reduced by 2.5-fold. The Sabin 3 mutant did not alter the maximum rate of eIF4A-dependent helicase activity, suggesting that this mutant primarily reduces the affinity, rather than activity, of the unwinding complex. To confirm this affinity model of attenuation, we show that eIF4G overexpression in HeLa cells overcomes the attenuation of a Sabin 3 mutant PV-luciferase replicon. Our study provides a quantitative framework for understanding the mechanism of PV Sabin attenuation and provides an explanation for the previously observed cell type-specific translational attenuation.