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Purpose: This article reflects on the adaption of Sarah Pink's video re-enactment methodology for exploring children's out-of-school lifeworlds. Design/methodology/approach: Video re-enactments originate in the work of Sarah Pink who developed the methodology to study everyday routines, including activities associated with people's energy consumption at home. This article discusses the adaption of this methodology for exploring 9–10-year-old children's out-of-school lifeworlds in their homes in the global cities of Hong Kong, Melbourne and Singapore. Findings: The article reflects on the practical ways in which the video re-enactment methodology was adapted to explore children's out-of-school activities in the three different locations. In terms of activities, the findings highlight that children's out-of-school lifeworlds included regular routines across a week that contribute to and constitute their everyday activities, with varying time spent on leisure, homework and scheduled activities. Originality/value: The authors discuss and reflect on the implications of adapting a methodology in order to make it relevant and innovative in a new research context. The use of video re-enactments with children to explore their out-of-school activities gives greater insights into their lifeworlds and their engagement in various activities and the opportunity for children to reflect on their everyday lives.

RNA modifications are widespread in biology and abundant in ribosomal RNA. However, the importance of these modifications is not well understood. We show that methylation of a single nucleotide, in the catalytic center of the large subunit, gates ribosome assembly. Massively parallel mutational scanning of the essential nuclear GTPase Nog2 identified important interactions with rRNA, particularly with the 2′-O-methylated A-site base Gm2922. We found that methylation of G2922 is needed for assembly and efficient nuclear export of the large subunit. Critically, we identified single amino acid changes in Nog2 that completely bypass dependence on G2922 methylation and used cryoelectron microscopy to directly visualize how methylation flips Gm2922 into the active site channel of Nog2. This work demonstrates that a single RNA modification is a critical checkpoint in ribosome biogenesis, suggesting that such modifications can play an important role in regulation and assembly of macromolecular machines.

Abstract:There is growing recognition of the critical role that refugee fathers have in helping their children and families adjust to starting life in a new country, and the contribution of their mental and physical health to settlement and family health outcomes. The aims of this systematic review were to summarize and critically appraise the quality of research reporting on estimates of mental and physical health conditions among refugee fathers. Electronic databases were systematically searched to identify peer-reviewed studies reporting on the mental and/or physical health of refugee fathers of children aged 0–18 years, who had settled in a host country. Study details and estimates of mental and/or physical health conditions were extracted, and a critical appraisal of study quality conducted. Ten studies reporting estimates of post-traumatic stress (2–86%) and general psychological distress, anxiety, depression, stress and prolonged grief (25–50%) were identified. Only one study reported on physical health. Study quality and variability in recruitment, samples, data collection methods and outcomes across studies made it difficult to estimate the overall prevalence of mental and physical health difficulties. Despite marked heterogeneity across studies, this review highlights that mental health difficulties among refugee fathers are common, identifying them as a specific cohort of socially and culturally diverse fathers at risk of poor health. The findings underscore the need for health and social policy and service delivery specifically focussed on promoting the mental health of refugee fathers and their families.Résumé:On reconnaît de plus en plus que les pères réfugiés jouent un rôle essentiel auprès de leurs enfants et de leur famille pour qu'ils s'adaptent et construisent une nouvelle vie, et que leur santé mentale et physique contribue à la réussite de l'installation et à la santé de leur famille. Cette revue systématique avait pour objectif de résumer et d'évaluer de manière critique la qualité des rapports de recherche sur les problèmes de santé mentale et physique chez les pères réfugiés. Afin d'identifier les études évaluées par des pairs portant sur la santé mentale et/ou physique des pères réfugiés d'enfants âgés de 0 à 18 ans et installés dans un pays d'accueil, des bases de données électroniques ont été systématiquement consultées. Les détails de l'étude et le compte rendu des problèmes de santé mentale et/ou physique ont été extraits, puis une évaluation critique de la qualité de l'étude effectuée. Dix études faisant état de stress post-traumatique (2–86%) et de détresse psychologique générale, d'anxiété, de dépression, de stress et de douleur prolongée (25–50%) ont été identifiées. Seule une étude mentionnait la santé physique. En raison de la qualité des études et de la variabilité du recrutement, des échantillons, des modes de collecte des données et des résultats, il a été difficile d'estimer la prévalence globale des problèmes de santé mentale et physique. Malgré une hétérogénéité marquée entre les études, cette revue révèle que les problèmes de santé mentale chez les pères réfugiés sont courants. Elle les identifie comme une cohorte spécifique de pères issus de milieux sociaux et culturels divers dont la santé est à risque. Les résultats soulignent la nécessité de politiques sanitaires et sociales et de prestations de services spécifiquement axées sur la promotion de la santé mentale des pères réfugiés et de leur famille.

Realist interviews are a data collection method used in realist evaluations. There is little available guidance for realist interviewing in cross-cultural contexts. Few published realist evaluations have included cross-cultural interviews, providing limited analyses of the cross-cultural application of realist methodology. This study integrated realist and cross-cultural qualitative methods in a realist evaluation of an Australian doula support program. The interviews were conducted with Arabic speaking clients of the program. The process included collaboration with a bicultural researcher, philosophically situating the study for methodologically coherent integration, bicultural review of the appropriateness of realist ‘how’ and ‘why’ questions, decisions about language translation and interpretation, pilot interviews, and co-facilitation of the interviews. Integration of the methods was feasible and valuable. This study may support other realist evaluators to give voice to people from culturally diverse groups, in a manner that is culturally safe, methodologically coherent and rigorous, and that produces trustworthy results.

RAS is a major anticancer drug target which requires membrane localization to activate downstream signal transduction. The direct inhibition of RAS has proven to be challenging. Here, we present a novel strategy for targeting RAS by stabilizing its interaction with the prenyl-binding protein PDE6D and disrupting its localization. Using rationally designed RAS point mutations, we were able to stabilize the RAS:PDE6D complex by increasing the affinity of RAS for PDE6D, which resulted in the redirection of RAS to the cytoplasm and the primary cilium and inhibition of oncogenic RAS/ERK signaling. We developed an SPR fragment screening and identified fragments that bind at the KRAS:PDE6D interface, as shown through cocrystal structures. Finally, we show that the stoichiometric ratios of KRAS:PDE6D vary in different cell lines, suggesting that the impact of this strategy might be cell-type-dependent. This study forms the foundation from which a potential anticancer small-molecule

The PI3K pathway is commonly activated in breast cancer, with PI3K-AKT pathway inhibitors used clinically. However, mechanisms that limit or enhance the therapeutic effects of PI3K-AKT inhibitors are poorly understood at a genome-wide level. Parallel CRISPR screens in 3 PTEN-null breast cancer cell lines identified genes mediating resistance to capivasertib (AKT inhibitor) and AZD8186 (PI3Kβ inhibitor). The dominant mechanism causing resistance is reactivated PI3K-AKT-mTOR signalling, but not other canonical signalling pathways. Deletion of TSC1/2conferred resistance to PI3Kβi and AKTi through mTORC1. However, deletion of PIK3R2and INPPL1drove specific PI3Kβi resistance through AKT. Conversely deletion of PIK3CA, ERBB2, ERBB3 increased PI3Kβi sensitivity while modulation of RRAGC, LAMTOR1, LAMTOR4increased AKTi sensitivity. Significantly, we found that Mcl-1loss enhanced response through rapid apoptosis induction with AKTi and PI3Kβi in both sensitive and drug resistant TSC1/2null cells. The combination effect was BAKbut not BAXdependent. The Mcl-1i + PI3Kβ/AKTi combination was effective across a panel of breast cancer cell lines with PIK3CAand PTENmutations, and delivered increased anti-tumor benefit in vivo. This study demonstrates that different resistance drivers to PI3Kβi and AKTi converge to reactivate PI3K-AKT or mTOR signalling and combined inhibition of Mcl-1 and PI3K-AKT has potential as a treatment strategy for PI3Kβi/AKTi sensitive and resistant breast tumours.

The Internet of Things is reshaping many households’ digital landscape and influencing children’s play and learning, especially in the form of toys that are named the Internet of Toys (IoToys). IoToys may generate a significant influence on children’s growth. While increasing attention is drawn to the IoToys, confusion around their conceptualization and use is evident. Without a thorough understanding of what the IoToys are, the progress of meaningful research on this topic will be greatly hindered. We, thus, conducted a systematic review to determine existing definitions of the IoToys using seven major databases over the past 20 years. After analyzing the definitions identified, we found that the previous definitions neglected the significance of defining “toys” in their work. The review led to a discussion around how to understand “toys” and then a more precise conceptualization of the IoToys, based on which implications for future research are offered.

In this colloquium we share stories from two schools located in Western Australia that were inspired from the Reggio Emilia education project. The focus is on a view of children as capable citizens of the now. The examples in practice describe learning scenarios in which educators work as researchers using the ordinary moments of daily classroom life. It is in these ordinary moments where a pedagogy of listening is enacted.

Two paralogs of the guanine dissociation inhibitor-like solubilizing factors UNC119, UNC119A and UNC119B, are present in the human genome. UNC119 binds to N-myristoylated proteins and masks the hydrophobic lipid from the hydrophilic cytosol, facilitating trafficking between different membranes. Two classes of UNC119 cargo proteins have been classified: low affinity cargoes, released by the Arf-like proteins ARL2 and ARL3, and high affinity cargoes, which are specifically released by ARL3 and trafficked to either the primary cilium or the immunological synapse. The UNC119 homologues have reported differences in functionality, but the structural and biochemical bases for these differences are unknown. Using myristoylated peptide binding and release assays, we show that peptides sharing the previously identified UNC119A high affinity motif show significant variations of binding affinities to UNC119B of up to 427-fold. Furthermore, we solve the first two crystal structures of UNC119B, one in complex with the high affinity cargo peptide of LCK and a second one in complex with the release factor ARL3. Using these novel structures, we identify a stretch of negatively charged amino acids unique to UNC119B that may undergo a conformational change following binding of a release factor which we propose as an additional release mechanism specific to UNC119B.

This review will identify, critically appraise, and synthesise evidence on culturally competent approaches to the provision of primary care to women of immigrant and refugee backgrounds who experience family and domestic violence.

Purpose: The purpose of this article is to contribute to the research methodology literature that arose out of the (new) sociology of childhood and the UN Convention of the Rights of the Child (1989) with regard to conducting ethical research withchildren rather than onchildren. In particular, this article reflects on the development of a method (learning dialogues). Design/methodology/approach: Learning dialogues were designed to enable children to share their responses to prompts about specific aspects of their lifeworlds. This was one method used to produce the data corpus which also included a large-scale survey, classroom ethnographies and (video) re-enactments of children's lives after school. Findings: The piloting of the learning dialogues took place in several iterations and a particular form was used for the main study. The original idea and development of the learning dialogues highlights they were both a rich source of data that complemented the other data sources in the study and an activity that children indicated that they enjoyed. The authors discuss the practicalities involved with adapting a qualitative method to different settings and to projects with large numbers of children. Originality/value: The conceptualisation of the learning dialogues as sources of personal documentation about aspects of children's lifeworlds was unique to this research. In thinking about the learning dialogues as one source of data within a broader project, the research aimed to be more inclusive of all participants in contributing to the findings produced in the project.

The contemporary air‐sea flux of CO2is investigated by the use of an air‐sea flux equation, with particular attention to the uncertainties in global values and their origin with respect to that equation. In particular, uncertainties deriving from the transfer velocity and from sparse upper ocean sampling are investigated. Eight formulations of air‐sea gas transfer velocity are used to evaluate the combined standard uncertainty resulting from several sources of error. Depending on expert opinion, a standard uncertainty in transfer velocity of either ~5% or ~10% can be argued and that will contribute a proportional error in air‐sea flux. The limited sampling of upper ocean fCO2is readily apparent in the Surface Ocean CO2Atlas databases. The effect of sparse sampling on the calculated fluxes was investigated by a bootstrap method, that is, treating each ship cruise to an oceanic region as a random episode and creating 10 synthetic data sets by randomly selecting episodes with replacement. Convincing values of global net air‐sea flux can only be achieved using upper ocean data collected over several decades but referenced to a standard year. The global annual referenced values are robust to sparse sampling, but seasonal and regional values exhibit more sampling uncertainty. Additional uncertainties are related to thermal and haline effects and to aspects of air‐sea gas exchange not captured by standard models. An estimate of global net CO2exchange referenced to 2010 of −3.0 ± 0.6 Pg C/year is proposed, where the uncertainty derives primarily from uncertainty in the transfer velocity. The oceanic carbon sink reduces the rate of accumulation of CO2in the atmosphere but is also responsible for the acidification of the ocean. One method of estimating the size of the oceanic carbon sink depends on a calculation of upward and downward flows of CO2at the sea surface. This study revisits this calculation using updated knowledge of the transfer processes at the sea surface and the results of a large international collaborative effort (Surface Ocean CO2Atlas) to collect and compile measurements of CO2in the upper ocean. Greater sampling of the oceans improves estimates, but direct calculation in each year is not practical. Instead, we calculate fluxes in a recent year (2010) using upper ocean measurements of CO2over many years. The remaining uncertainty is dominated by limited knowledge of the efficiency of stirring of gas across the sea surface, the air‐sea transfer velocity. The study suggests a relatively large downward flow of CO2into the ocean compared to previous applications of this method and other methods to estimate the oceanic carbon sink. Increased knowledge is rewarded by reduced uncertainty in the net global flux; that flux is estimated at −3.0 ± 0.6 Pg C/year. Further understanding of transfer velocities and better sampling may reduce the uncertainty in the future. Increased understanding of air‐sea gas transfer processes and better sampling of the upper ocean enables higher confidence in calculations of air‐sea CO2fluxesThe calculations imply a relatively large global net air‐to‐sea flux of −3.0 Pg C/year (referenced to 2010)This flux is known within 0.6 Pg C/year, where uncertainty in air‐sea transfer velocity is the largest contribution to the combined uncertainty

In this study, we hypothesized that replacing conventional milk, which contains A1 and A2 ß-casein proteins, with milk that contains only A2 ß-casein in the diet of dairy or milk-intolerant preschoolers (age 5 to 6 years) would result in reduced gastrointestinal symptoms associated with milk intolerance, and that this would correspond with cognitive improvements. This randomized, double-blind, crossover study aimed to compare the effects of 5 days’ consumption of conventional milk versus milk containing only A2 ß-casein on gastrointestinal symptoms, as assessed via visual analog scales, average stool frequency and consistency, and serum inflammatory and immune biomarkers in healthy preschoolers with mild-to-moderate milk intolerance. The study also aimed to compare changes in the cognitive behavior of preschoolers, based on Subtle Cognitive Impairment Test scores. Subjects who consumed milk containing only A2 ß-casein had significantly less severe gastrointestinal symptoms as measured by visual analog scales, reduced stool frequency, and improvements in stool consistency, compared with subjects consuming conventional milk. There were significant increases from baseline in serum interleukin-4, immunoglobulins G, E, and G1, and beta-casomorphin-7 coupled to lower glutathione levels, in subjects consuming conventional milk compared with milk containing only A2 ß-casein. Subtle Cognitive Impairment Test analysis showed significant improvements in test accuracy after consumption of milk containing only A2 ß-casein. There were no severe adverse events related to consumption of either milk product. Replacing conventional milk with milk containing only A2 ß-casein reduced gastrointestinal symptoms associated with milk intolerance in Chinese preschool children, with corresponding improvements in aspects of cognitive performance.

This study presents an investigation into the impact of varied burner staging environments on an oxy-fuel flame and the rate of the NO formation and destruction processes. The experimental data were extracted from the use of a 250 kWthdown-fired combustion test facility with a scaled-down model of an industrial low-NOxburner. Two oxy-coal combustion regimes were investigated by varying a fixed flow of oxidant between the secondary and tertiary registers, so as to impact the stoichiometry in the fuel-rich region and flame structure, and using various NO recycling regimes, to test the impact of these different burner configurations on NO reburning. The data were collected by monitoring key emissions in the flue gas and in the flame, as well as temperatures throughout the furnace and the unburned carbon content of the ash. A detailed investigation encompassing the impact of secondary oxidant proportion for different oxidants on NO emissions, together with the quantification of recycled NO destruction, is discussed. This investigation finds that 85–95% of the recycled NO is destroyed at a range of burner configurations using OF 27 and OF 30 at 170 kWth. In addition to this, NO formation and carbon burnout are found to be significantly affected with changing burner configurations. Further to this, OF 30 flames appear to be more sensitive to burner configuration than OF 27 flames with regards to both NO formation and destruction, possibly due to the decreased density of the OF 30 oxidant. Radial profiles of two burner configurations at OF 27 and OF 30, as well as an axial profile of two burner configurations at OF 30, were analyzed. The profiles appear to show that burner staging aids in controlling the products of NO reburning, hence maximizing the destruction of recycled NO.

Despite nearly three decades of the use of new technologies in education, schools seem to have remained impervious to significant change. Heritage curriculum and traditional pedagogies persist and, indeed, are dominant in school contexts, which seem to be embedded in the past, rather than preparing children for their future lives. Pockets of innovation illustrate that transformation is possible and comes with the added benefits of renewed student enthusiasm and engagement in learning. Yet, systemic changes are limited in a global context that is dominated by high stakes testing and the neo-liberal agenda. This article explores the potential for change. Focusing on the early years, which are the foundation of schooling, we report on data from a study using iPads for learning with kindergarten children in Australia (4 and 5 years of age). The data support the contention that new technologies offer the possibility for new learning by enabling young children to embark on investigations and explorations that were not possible in previous eras. In this article, we focus on transformations and explore the potential of the iPads to encourage playful explorations for investigating, reflecting, making meaning, knowledge building, and communicating ideas to a shared audience.

Background Patients with Crohn’s disease (CD) frequently complain of cognitive difficulties such as problems with concentration and clouding of thought, yet this has scarcely been objectively defined and underlying mechanisms remain unknown.Objective The objective of this article is to objectively measure cognitive impairments in patients with CD compared with healthy controls, and if present, to identify potentially modifiable, contributing factors associated with cognitive impairment.Methods CD patients and healthy age-/sex-matched controls completed surveys encompassing clinical, demographic, psychiatric, fatigue and sleep parameters. Contemporaneously, disease activity assessment with serum CRP, faecal calprotectin, Harvey–Bradshaw Index and the Subtle Cognitive Impairment test (SCIT) were performed, with the primary measure of response time (SCIT-RT) compared between groups. Multiple linear regression assessed for factors associated with slower SCIT-RT, denoting subtle cognitive impairment.Results A total of 49 CD and 31 control individuals participated, with median age 44 years (range 22–65) and 43 years (21–63), respectively. Compared to controls, SCIT-RT was slower across all timepoints in CD patients (ANOVA p< 0.001). In multivariate analysis, serum CRP (standardised beta coefficient 0.27, 95% CI (0.02, 0.51)), abdominal pain (0.43 (0.16, 0.70)), plasma haemoglobin (1.55 (1.42, 1.68)), and concurrent fatigue (0.56 (0.25, 0.88)) were each independently associated with slower SCIT-RT in CD (each p< 0.05), with a trend for poorer sleep quality 0.54 (−0.03, 1.11) (p= 0.06), yet conversely, higher faecal calprotectin titres were associated with faster SCIT-RT (−1.77 (−1.79, −1.76), p< 0.01).Conclusions Patients with CD demonstrated subtle cognitive impairment utilising the objective SCIT, correlating with systemic inflammation and other disease burden measures, although higher faecal calprotectin titres were unexpectedly associated with less cognitive impairment.

Patients with Crohn’s disease (CD) frequently complain of cognitive difficulties such as problems with concentration and clouding of thought, yet this has scarcely been objectively defined and underlying mechanisms remain unknown. The objective of this article is to objectively measure cognitive impairments in patients with CD compared with healthy controls, and if present, to identify potentially modifiable, contributing factors associated with cognitive impairment. CD patients and healthy age-/sex-matched controls completed surveys encompassing clinical, demographic, psychiatric, fatigue and sleep parameters. Contemporaneously, disease activity assessment with serum CRP, faecal calprotectin, Harvey–Bradshaw Index and the Subtle Cognitive Impairment test (SCIT) were performed, with the primary measure of response time (SCIT-RT) compared between groups. Multiple linear regression assessed for factors associated with slower SCIT-RT, denoting subtle cognitive impairment. A total of 49 CD and 31 control individuals participated, with median age 44 years (range 22–65) and 43 years (21–63), respectively. Compared to controls, SCIT-RT was slower across all timepoints in CD patients (ANOVA p?

Objective The efficacy of low-level laser treatment (LLLT) for chronic back pain remains controversial due to insufficient trial data. We aimed to conduct an updated review to determine if LLLT (including laser acupuncture) has specific benefits in chronic non-specific low back pain (CNLBP).Methods Electronic databases were searched for randomised trials using sham controls and blinded assessment examining the intervention of LLLT in adults with CNLBP. Primary outcomes were pain and global assessment of improvement with up to short-term follow-up. Secondary outcomes were disability, range of back movement, and adverse effects. A random effects meta-analysis was conducted. Subgroup analyses were based on laser dose, duration of baseline pain, and whether or not laser therapy used an acupuncture approach.Results 15 studies were selected involving 1039 participants. At immediate and short-term follow-up there was significant pain reduction of up to WMD (weighted mean difference) -1.40 cm (95% CI -1.91 to -0.88 cm) in favour of laser treatment, occurring in trials using at least 3 Joules (J) per point, with baseline pain <30 months and in non-acupuncture LLLT trials. Global assessment showed a risk ratio of 2.16 (95% CI 1.61 to 2.90) in favour of laser treatment in the same groups only at immediate follow-up.Conclusions We demonstrated moderate quality of evidence (GRADE) to support a clinically important benefit in LLLT for CNLBP in the short term, which was only seen following higher laser dose interventions and in participants with a shorter duration of back pain. Rigorously blinded trials using appropriate laser dosage would provide greater certainty around this conclusion.

Objective:To investigate the extent to which Aboriginal women access primary care for themselves and their infant in the year after childbirth. Method:Cross sectional population‐based survey of women giving birth to Aboriginal babies in South Australia between July 2011 and June 2013. Results:A total of 344 women took part in the study 4–9 months after giving birth. The majority had seen a primary health care practitioner since the birth: 86% had seen a Child and Family Health Service (CaFHS) nurse, 81% a general practitioner (GP), and 61% an Aboriginal health worker (AHW). Women living in remote areas were more likely to have seen primary care practitioners than women living in Adelaide (GP: OR 2.3, 95% CI 1.0–5.2; CaFHS: OR 2.4, 95% CI 1.0–5.8; AHW: OR 5.2, 95% CI 2.8–9.8). Around 16% of women with gestational diabetes and 10% with hypertension had not seen a GP since the birth, and 24% of women who had a low birthweight infant had not seen a CaFHS nurse. Conclusions:Despite high prevalence of maternal and infant morbidity, a sizeable minority of women did not access primary care practitioners postpartum. Implications for public health:Stronger efforts are needed to ensure Aboriginal women and families receive appropriate postnatal follow‐up.

To investigate the extent to which Aboriginal women access primary care for themselves and their infant in the year after childbirth.