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Demographic research tends to track child mortality conditions with annualized death rates, paying little mind to how these annualized rates reflect in the lives of the surviving population. Yet, demography’s age-old interest in how exposure to child mortality affects individuals’ perceptions, decisions, and behaviors, and ultimately macro-level population processes, raises questions about how pervasive intimate experiences of child death remain across the globe—particularly in low- and middle-income countries where declines in mortality are recent. In this paper, we document women’s experiences of under-five mortality in 50 low- and middle-income countries, focusing comprehensively on experiences in their immediate natal or conjugal family in the form of sibling or offspring death. Specifically, we analyze Demographic and Health Survey Program data on 1.05 million women spanning three decadal birth cohorts to document women’s life-course exposure to under-five sibling or offspring death, the intergenerational clustering of these experiences, and how they are (not) changing across cohorts. The results show an exceedingly high, and often stable, percentage of women have experienced under-five sibling and offspring deaths. Moreover, women’s risk of offspring death is often strongly associated with their history of sibling death; this strong intergenerational clustering has remained stable, or has grown larger, across cohorts in most countries.

Background Appropriate tracing methods for sentinel lymph node biopsy (SLNB) play a key role in accurate axillary staging. This prospective, non-inferiority, phase III RCT compared the feasibility and diagnostic performance of ultrasound-assisted carbon nanoparticle suspension (CNS) mapping with dual tracer-guided SLNB in patients with early breast cancer. Methods Eligible patients had primary breast cancer without nodal involvement (cN0), or had clinically positive lymph nodes (cN1) that were downstaged to cN0 after neoadjuvant chemotherapy. Patients were randomly assigned (1 : 1) to undergo either ultrasound-assisted CNS sentinel lymph node (SLN) mapping (UC group) or dual tracer-guided mapping with CNS plus indocyanine green (ICG) (GC group). The primary endpoint was the SLN identification rate. Results Between 1 December 2019 and 30 April 2021, 330 patients were assigned randomly to the UC (163 patients) or GC (167 patients) group. The SLN identification rate was 94.5 (95 per cent c.i. 90.9 to 98.0) per cent in the UC group and 95.8 (92.7 to 98.9) per cent in the GC group. The observed difference of –1.3 (–5.9 to 3.3) per cent was lower than the prespecified non-inferiority margin of 6 per cent (Pnon–inferiority = 0.024). No significant difference was observed in metastatic node rate (30.5 versus 24.4 per cent; P = 0.222), median number of SLNs harvested (3 (range 1–7) versus 3 (1–8); P = 0.181), or duration of surgery (mean(s.d.) 7.53(2.77) versus 7.63(3.27) min; P = 0.316) between the groups. Among the subgroup of patients who had undergone neoadjuvant treatment, the SLN identification rate was 91.7 (82.2 to 100) per cent in the UC group and 90.7 (81.7 to 99.7) per cent in the GC group. Conclusion The diagnostic performance of ultrasound-assisted CNS mapping was non-inferior to that of dual tracer-guided SLN mapping with CNS plus ICG in patients with early breast cancer. Registration number NCT04951245 (http://www.clinicaltrials.gov).

BACKGROUND Outdoor play is critical to children’s healthy development and well-being. Early learning and childcare centers (ELCCs) are important venues for increasing children’s outdoor play opportunities, and early childhood educators’ (ECE) perception of outdoor play can be a major barrier to outdoor play. The OutsidePlay-ECE risk-reframing intervention is a fully automated and open access web-based intervention to reframe ECEs’ perceptions of the importance of outdoor play and risk in play and to promote a change in their practice in supporting it in ELCC settings. We grounded the intervention in social cognitive theory and behavior change techniques. OBJECTIVE The aim of this study is to evaluate the effectiveness of the OutsidePlay-ECE web-based risk-reframing intervention. METHODS We conducted a single-blind randomized controlled trial in Canada between December 2020 and June 2021 to test the OutsidePlay-ECE risk-reframing intervention for ECEs. We recruited participants using social media and mass emails through our partner and professional networks. We invited ECEs and administrators working in an ELCC, who can speak, read, and understand English. We randomized consented participants to the intervention or control condition. The participants allocated to the intervention condition received a link to the OutsidePlay-ECE intervention. Participants allocated to the control condition read the Position Statement on Active Outdoor Play, a 4-page document on research and recommendations for action in addressing barriers to outdoor play. The primary outcome was a change in tolerance of risk in play. The secondary outcome was goal attainment. We collected data on the web via REDCap (Vanderbilt University) at baseline and 1 week and 3 months after intervention. RESULTS A total of 563 participants completed the baseline survey, which assessed their demographics and tolerance of risk in play. They were then randomized: 281 (49.9%) to the intervention and 282 (50.1%) to the control condition. Of these, 136 (48.4%) and 220 (78%) participants completed the baseline requirements for the intervention and control conditions, respectively. At 1 week after intervention, 126 (44.8%) and 209 (74.1%) participants completed follow-up assessments, respectively, and at 3 months after intervention, 119 (42.3%) and 195 (69.1%) participants completed the assessments, respectively. Compared with participants in the control condition, participants in the intervention group had significantly higher tolerance of risk in play at 1 week (β=.320; P=.001) and 3 months after intervention (β=.251; P=.009). Intention-to-treat analyses replicated these findings (β=.335; Pβ=.271; P=.004, respectively). No significant intervention effect was found for goal attainment outcomes (odds ratio 1.124, 95% CI 0.335-3.774; P=.85). CONCLUSIONS The results of this randomized controlled trial demonstrated that the OutsidePlay-ECE intervention was effective and had a sustained effect in increasing ECEs’ and administrators’ tolerance of risk in play. It was not effective in increasing goal attainment. CLINICALTRIAL ClinicalTrials.gov NCT04624932; https://clinicaltrials.gov/ct2/show/NCT04624932 INTERNATIONAL REGISTERED REPORT RR2-10.2196/31041

Background and AimGuidelines recommended that cardiac index (CI) of term infants with septic shock should reach the target level of 3.3–6.0L/(min⋅m2). However, there are still no standard values for preterm infants with septic shock. Herein, we investigated the functional echocardiographic baseline values of left ventricular (LV) systolic functional parameters at the onset of septic shock in preterm infants and possible correlations between baseline values and poor outcomes.Materials and MethodsThis was a prospective, observational, and longitudinal single-center study. Eligible infants were monitored for LV systolic functional parameters using functional echocardiography at the onset of septic shock. The primary study outcome was the difference in the baseline value of LV systolic functional parameters in preterm infants with septic shock with different gestational age (GA) and birth weight (BW). The secondary outcome was septic shock-associated death or severe brain injury (including grade 3–4 intraventricular hemorrhage or periventricular leukomalacia).ResultsIn total, 43 subjects met the criteria, with a median GA of 321/7 weeks and BW of 1800 grams. No difference was observed in baseline values of LV systolic functional parameters among infants with different GA and BW. Infants were assigned to good and poor outcomes groups based on septic shock-associated death or severe brain injury. Out of 43 infants, 29 (67.4%) had good outcomes vs. 14 (32.6%) with poor outcomes. Stroke index (SI) [18.2 (11.1, 18.9) mL/m2 vs. 23.5 (18.9, 25.8) mL/m2, p = 0.017] and cardiac index (CI)[2.7 (1.6, 3.5) L/(min⋅m2) vs. 3.4 (3.0, 4.8) L/(min⋅m2), p = 0.015] in infants with poor outcomes were significantly lower (P < 0.05). Receiver operating characteristic (ROC) curve analysis showed that the cut-off values of SI and CI for predicting poor outcomes in preterm infants with septic shock were 19.5 mL/m2 (sensitivity, 73.9%; specificity, 81.8%) and 2.9L/(min⋅m2) (sensitivity, 78.3%; specificity, 72.7%), with area under the ROC curve (AUC) value of 0.755 and 0.759, respectively.ConclusionThere were no differences in baseline LV systolic functional values among preterm infants with septic shock with different GA and BW. However, preterm infants with SI2 and/or CI2) at the onset of septic shock were at high risk of having poor outcomes.

Given the potential importance of social environment on obesity and to better understand their causal relationship amongst children and adolescents, this scoping review systematically searches for and evaluates programs and interventions using natural experiment designs. A majority of the studies assessing peer and social norm effects reported significant findings. Peer effects with nontrivial effect sizes likely have practical implications for interventions, while a strong conclusion cannot be drawn for social norm and neighborhood safety effects. Leveraging naturally occurring data might provide future research with a promising way of establishing a more robust causal inference for the topic of interest.

Background: Recent studies showed homologous recombination deficiency (HRD) status may correlate with pathological complete response (pCR) rate. However, whether HRD specifically predicts platinum chemotherapy efficacy or predicts pCR benefit irrespective of treatment regimen remains unclear. Methods: This meta-analysis aimed to determine the predictive value of HRD on pCR in patients with triple-negative breast cancer (TNBC) receiving platinum-based neoadjuvant chemotherapy (NCT). Published articles were searched on PubMed, Embase, Medline, Web of Science, and Cochrane database up to June 1, 2021 and studies reporting pCR rate for HRD carriers on platinum-based NCT selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined for pCR, clinical response rates and grade 3 or higher adverse events (AEs) using the random-effects model. Bias risk was evaluated using Cochrane Collaboration’s tool. Findings: Seven studies were eligible. Results showed that HRD carriers had higher pCR rates than non-HRD carriers across all treatment arms (OR 3.35, 95% CI 1.93 – 5.81, p < 0.01). In HRD carriers, pCR rate was higher in patients on platinum-based NCT relative to those without platinum exposure (OR 1.95, 95% CI 1.17 – 3.23, p = 0.01). We did not observe marked pCR improvements in non-HRD carriers. PCR rates in breast cancer susceptibility gene (BRCA) mutant relative to the BRCA wild-type group did not differ significantly in HRD carriers on platinum-based NCT (OR 1.84, 95% CI 0.84 – 4.02, p = 0.12). Interpretation: HRD carriers correlated with higher pCR in TNBC patients on platinum-based NCT irrespective of BRCA status. In non-HRD carriers, adding platinum to NCT was associated with elevated AEs rather than improved therapeutic effect. Registration Information: PROSPERO, registration number CRD420212498740. Funding Information: This study was supported by grants from National Natural Science Foundation of China (82171898)，Science and Technology Planning Project of Guangzhou City (202002030236), Beijing Medical Award Foundation(YXJL-2020-0941-0758), Science and Technology Special Fund of Guangdong Provincial People's Hospital (No.Y012018218), CSCO-Hengrui Cancer Research Fund (Y-HR2016-067), Medical Scientific Research Foundation of Guangdong Province (B2021406), and Guangdong Provincial Department of Education Characteristic Innovation Project（2015KTSCX080. Declaration of Interests: We declare no competing interests.

BACKGROUND Outdoor risky play, such as climbing, racing, and independent exploration, is an important part of childhood and is associated with various positive physical, mental, and developmental outcomes for children. Parental attitudes and fears, particularly mothers’, are a major deterrent to children’s opportunities for outdoor risky play. OBJECTIVE The aim of this study was to evaluate the efficacy of 2 versions of an intervention to reframe mothers’ perceptions of risk and change parenting behaviors: a web-based intervention or an in-person workshop, compared with the control condition. METHODS The Go Play Outside! randomized controlled trial was conducted in Canada from 2017 to 2018. Participants were recruited through social media, snowball sampling, and community notices. Mothers of children aged 6-12 years were self-assessed through eligibility questions, and those eligible and consented to participate in the study were randomized into a fully automated web-based intervention, the in-person workshop, or the control condition. The intervention was underpinned by social cognitive theory, incorporating behavior change techniques. Participants progressed through a series of self-reflection exercises and developed a goal for change. Control participants received the Position Statement on Active Outdoor Play. The primary outcome was increase in tolerance of risky play and the secondary outcome was goal attainment. Data were collected online via REDCap at baseline, 1 week, and 3 months after the intervention. Randomization was conducted using sealed envelope. Allocations were concealed to researchers at assignment and data analysis. We conducted mediation analyses to examine whether the intervention influenced elements of social cognitive theory, as hypothesized. RESULTS A total of 451 mothers were randomized and completed baseline sociodemographic assessments: 150 in the web-based intervention, 153 in the in-person workshop, and 148 in the control condition. Among these, a total of 351 mothers completed the intervention. At 1 week after the intervention, 113, 85, and 135 mothers completed assessments for each condition, respectively, and at 3 months after the intervention, 105, 84, and 123 completed the assessments, respectively. Compared with mothers in the control condition, mothers in the web-based intervention had significantly higher tolerance of risky play at 1 week (P=.004) and 3 months after the intervention (P=.007); and mothers in the in-person workshop had significantly higher tolerance of risky play at 1 week after the intervention (P=.02). No other significant outcomes were found. None of the potential mediators were found to significantly mediate the outcomes. CONCLUSIONS The trial demonstrates that the web-based intervention was effective in increasing mothers’ tolerance for risk in play. CLINICALTRIAL ClinicalTrials.gov NCT03374683; https://clinicaltrials.gov/ct2/show/NCT03374683 INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-018-2552-4

Objectives: To compare the clinical efficacy of heated, humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) in extremely low-birth-weight preterm infants (ELBWI) after extubation.Methods: This trial included 94 extremely low-birth-weight infants (ELBWI), within 7 days after birth, and prepared for tracheal extubation and a change to non-invasive ventilation in the neonatal intensive care unit (NICU) admitted to our hospital from January 2015 to December 2018, with 48 infants in the HHHFNC group and 46 infants in the NCPAP group. Reintubation rate within 72 h after initial extubation, total ventilation time, non-invasive ventilation time, total oxygen inhalation time, and the time to reach full enteral feeding were the primary outcome measures. Total intestinal feeding time, average weight gain rate, days of hospitalization, costs of hospitalization, and complication rates, including nasal injury, IVH, BPD, NEC, ROP, and PDA, were used as secondary outcomes. Data were analyzed using Student's t-test or the Mann-Whitney U-test with a Chi-square test or Fisher's exact test, as appropriate, in SPSS (25.0).Results: HHHFNC not only shortened the oxygen exposure time but also effectively reduced the incidence of nasal injury (6.25 vs. 36.96%) and NEC (10.42 vs. 28.26%) (P < 0.05). Additionally, HHHFNC achieved a significant advance in the time to reach full enteral feeding (31.24 ± 11.35 vs. 34.21 ± 14.09 days); increased the average weight gain rate (16.07 ± 3.10 vs. 13.74 ± 4.21) and reduced the days of hospitalization (73.45 ± 18.84 vs. 79.24 ± 19.75), with a lower cost of hospitalization (16.04 ± 3.64 vs.18.79 ± 4.13) thousand dollars (all P < 0.05).Conclusions: Compared with NCPAP, HHHFNC was effective in preventing extubation failure in mechanically ventilated preterm ELBWI. HHHFNC shortens oxygen consumption time and significantly reduces the incidence of nasal injury and necrotizing enterocolitis; moreover, it can also reduce the length of stay and the hospitalization costs.

Additional file 1: Appendix A: An expanded version of Table 3 that is shown in the manuscript. Appendix B: Food Parenting Item Bank Questionnaire. Appendix C.

PurposeThere has been a call to improve measurement rigour and standardization of food parenting practices measures, as well as aligning the measurement of food parenting practices with the parenting literature. Drawing from an expert-informed conceptual framework assessing three key domains of food parenting practices (autonomy promotion, control, and structure), this study combined factor analytic methods with Item Response Modeling (IRM) methodology to psychometrically validate responses to the Food Parenting Practice item bank.MethodsA sample of 799 Canadian parents of 5–12-year-old children completed the Food Parenting Practice item bank (129 items measuring 17 constructs). The factorial structure of the responses to the item bank was assessed with confirmatory factor analysis (CFA), confirmatory bi-factor item analysis, and IRM. Following these analyses, differential Item Functioning (DIF) and Differential Response Functioning (DRF) analyses were then used to test invariance properties by parents’ sex, income and ethnicity. Finally, the efficiency of the item bank was examined using computerized adaptive testing simulations to identify the items to include in a short form.ResultsOverall, the expert-informed conceptual framework was predominantly supported by the CFA as it retained the same 17 constructs included in the conceptual framework with the exception of the access/availability and permissive constructs which were respectively renamed covert control and accommodating the child to better reflect the content of the final solution. The bi-factor item analyses and IRM analyses revealed that the solution could be simplified to 11 unidimensional constructs and the full item bank included 86-items (empirical reliability from 0.78 to 0.96, except for 1 construct) and the short form had 48 items.ConclusionOverall the food parenting practice item bank has excellent psychometric properties. The item bank includes an expanded version and short version to meet various study needs. This study provides more efficient tools for assessing how food parenting practices influence child dietary behaviours. Next steps are to use the IRM calibrated item bank and draw on computerized adaptive testing methodology to administer the item bank and provide flexibility in item selection.

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Rabies, which is caused by the rabies virus (RABV), is an ancient zoonosis that has a high mortality rate. Previous studies have indicated that recombinant RABV expressing canine interleukin-6 (rHEP-CaIL6), induced more virus-neutralizing antibodies than parental RABV in mice following intramuscular immunization. To investigate the immune response induced in the CNS by rHEP-CaIL6 after intranasal or intracranial administration in mice, the permeability of the blood-brain barrier (BBB), the infiltration of CD3 T cells, and innate immune response-related effector molecules in the CNS were examined. It was observed that infection of rHEP-CaIL6 led to enhanced BBB permeability following intranasal infection. More CD3 T cells infiltrated into the central nervous system (CNS) in mice infected with rHEP-CaIL6 than in those infected with the HEP-Flury strain. Furthermore, rHEP-CaIL6 induced an increased expression of innate immune response-related effector molecules, compared with the parental HEP-Flury strain, within the CNS. Taken together, these findings suggest that rHEP-CaIL6 induced stronger immune responses in mice brains, which is more beneficial for virus clearance. These results may also partly illustrate the role of IL6 in RABV infection.

Background The purpose of this study was to investigate whether there is a bi-directional relationship between sleep characteristics (time in bed, sleep duration, sleep chronology, and sleep efficiency) and time spent participating in outdoor active play among children. Methods Participants consisted of 433 children aged 10–13 years from Kingston, ON, Canada. Time in bed, sleep duration, sleep chronology, and sleep efficiency were measured for 8 consecutive nights using data from a sleep log and Actical accelerometer. Outdoor active play was measured for the 7 days that fell in between these 8 nights using a combination of data from accelerometers, global positioning system loggers, and geographic information systems. Generalized estimating equation models were used to assess the relationships between sleep characteristics and outdoor active play. These models accounted for the repeated measures nested within participants and adjusted for several confounders (e.g., age, sex, family income, neighborhood traffic and green space). Results Time in bed, sleep duration, sleep chronology, and sleep efficiency were not significantly associated with the following day’s outdoor active play. There was a significant (p = 0.017) association between outdoor active play and the following night’s time in bed, which suggested that each hour increase in outdoor active play was associated with a 4.0 min increase in time in bed. Outdoor active play was not significantly associated with sleep duration, sleep chronology, or sleep efficiency. Conclusions None of the sleep characteristics predicted the following day’s outdoor active play. Increase time spent in outdoor active play predicted a longer time in bed, but not sleep duration, sleep chronology, or sleep efficiency.

Mobile-Health is increasingly used to deliver lifestyle modification interventions; however, little is known about how users engage with these apps. This study aims to profile how teens engage with Aim2Be– a lifestyles behavior modification app), characterize engagement profiles, and examine which engagement profiles support changes in behaviors (diet, physical activity, screen time and sleep) and changes in the mediators targeted by the app. Data were collected from 301 teens (14.8 years, 49% boys, 68% Caucasian) living in Canada, from March to October 2018, who utilized the Aim2Be app for 4.5 months. App-analytics tracked teen engagement with the app features (selecting aims, completing tasks and quick wins, using the knowledge center and social wall, and accessing the virtual coach). Factor mixture modeling identified the following engagement profiles: Uninvolved (32%) did not use most app features; Dabblers (25%) minimally used the app features; Engaged (24%) had moderate-to-high use of app features; and Keeners (19%) had the highest use of all app features. Regression models showed that teens were more engaged with Aim2Be if their parents were involved and if they participated with their mothers and/or an educated parent. Finally, Keeners significantly improved on most mediators of behavior change and increased their fruit and vegetable intake. The findings suggest that parental engagement supported teen engagement of the Aim2Be app and high engagement was needed to support behavior change among teens. Gaining a greater understanding of the features that appeal to teens is necessary to support behavior change.

BackgroundParental attitudes regarding child safety and risk engagement play important roles in child injury prevention and health promotion efforts. Few studies have compared mothers’ and fathers’ attitudes on these topics. This study used the risk engagement and protection survey (REPS) previously validated with fathers to compare with data collected from mothers.MethodsMulti-group confirmatory factor analysis was used with a sample of 234 mothers and 282 fathers. Eligible parents had a child 6–12 years attending a paediatric hospital for an injury-related or other reason. We tested the factor structure of the survey by examining configural, metric and scalar invariance. Following this, mothers’ and fathers’ mean scores on the two identified factors of child injury protection and risk engagement were compared.ResultsComparing mothers’ and fathers’ data showed the two-factor structure of the REPS held for the mothers’ data. Comparing mean scores for the two factors suggested that fathers and mothers held equivalent attitudes. For the combined sample, parent injury protection attitude scores were significantly higher for daughters versus sons. In addition, attitude scores were significantly lower for injury protection and higher for risk engagement among parents born in Canada compared with those who were not.ConclusionsThe REPS allows for valid assessment of injury protection and risk engagement factors for fathers and mothers. Mothers conceptualised the two factors as distinct concepts, similar to fathers. The REPS can be used to inform parenting programme development, implementation and evaluation.

Nucleoprotein (N) is a key element in rabies virus (RABV) replication. To further investigate the effect of N on RABV, we manipulated an infectious cDNA clone of the RABV HEP-Flury to rearrange the N gene from its wild-type position of 1 (N-P-M-G-L) to 2 (P-N-M-G-L), 3 (P-M-N-G-L), or 4 (P-M-G-N-L), using an approach that left the viral nucleotide sequence unaltered. Subsequently, viable viruses were recovered from each of the rearranged cDNA and examined for their gene expression levels, growth kinetics in cell culture, pathogenicity in suckling mice and protection in mice. The results showed that gene rearrangement decreased N mRNA transcription and vRNA replication. As a result, all viruses with rearranged genomes showed worse replication than that of rHEP-Flury in NA cells at a MOI of 0.01, but equivalent or slightly better replication levels at a MOI of 3. Consequently, the lethality in suckling mice infected with N4 was clearly attenuated compared with rHEP-Flury. However, the protection to mice was not enhanced. This study not only gives us insight into the understanding of the phenotype of RABV N gene rearrangement, but also helps with rabies vaccine candidate construction.

Background Outdoor risky play, such as climbing, racing, and independent exploration, is an important part of childhood and is associated with various positive physical, mental, and developmental outcomes for children. Parental attitudes and fears, particularly mothers’, are a major deterrent to children’s opportunities for outdoor risky play. Objective The aim of this study was to evaluate the efficacy of 2 versions of an intervention to reframe mothers’ perceptions of risk and change parenting behaviors: a web-based intervention or an in-person workshop, compared with the control condition. Methods The Go Play Outside! randomized controlled trial was conducted in Canada from 2017 to 2018. Participants were recruited through social media, snowball sampling, and community notices. Mothers of children aged 6-12 years were self-assessed through eligibility questions, and those eligible and consented to participate in the study were randomized into a fully automated web-based intervention, the in-person workshop, or the control condition. The intervention was underpinned by social cognitive theory, incorporating behavior change techniques. Participants progressed through a series of self-reflection exercises and developed a goal for change. Control participants received the Position Statement on Active Outdoor Play. The primary outcome was increase in tolerance of risky play and the secondary outcome was goal attainment. Data were collected online via REDCap at baseline, 1 week, and 3 months after the intervention. Randomization was conducted using sealed envelope. Allocations were concealed to researchers at assignment and data analysis. We conducted mediation analyses to examine whether the intervention influenced elements of social cognitive theory, as hypothesized. Results A total of 451 mothers were randomized and completed baseline sociodemographic assessments: 150 in the web-based intervention, 153 in the in-person workshop, and 148 in the control condition. Among these, a total of 351 mothers completed the intervention. At 1 week after the intervention, 113, 85, and 135 mothers completed assessments for each condition, respectively, and at 3 months after the intervention, 105, 84, and 123 completed the assessments, respectively. Compared with mothers in the control condition, mothers in the web-based intervention had significantly higher tolerance of risky play at 1 week (P=.004) and 3 months after the intervention (P=.007); and mothers in the in-person workshop had significantly higher tolerance of risky play at 1 week after the intervention (P=.02). No other significant outcomes were found. None of the potential mediators were found to significantly mediate the outcomes. Conclusions The trial demonstrates that the web-based intervention was effective in increasing mothers’ tolerance for risk in play. Trial Registration ClinicalTrials.gov NCT03374683; https://clinicaltrials.gov/ct2/show/NCT03374683 International Registered Report Identifier (IRRID) RR2-10.1186/s13063-018-2552-4

There has been increasing recognition of the importance of children's outdoor play and independent mobility for thriving children, neighbourhoods, cities and society, which has led to calls to reverse children's retreat from the street commonplace in many Western nations. We privilege the voices of children aged 10–13 living in three diverse neighbourhoods in an urban centre in Canada to examine the factors that influence children's unsupervised outdoor activities (UOA), such as play, hanging out, and active. A total of 105 children participated in go-along interviews. Analyses revealed two themes: First, ‘feeling safe’ encompassed a sense of social and physical safety, including children's sense of neighbourliness, social dangers, discomfort around traffic, and personal agency to keep themselves safe. Second, having ‘things to do,’ included the affordances that children perceived as important in their neighbourhoods, particularly having other children to play with, diverse amenities and access to nature, and opportunities for challenge and risky play. We outline a conceptual model of children's decision process for UOA that identifies key variables that influence children's engagement in UOA.

The purpose of this multinational and cross-sectional study was to investigate whether nighttime sleep duration was associated with physical activity (PA) and sedentary time (SED) the following day, whether daytime PA/SED were associated with sleep duration the subsequent night, and whether the associations were modified by sex and study sites. Data from 5779 children aged 9-11. years were analyzed. A waist-worn Actigraph GT3X. + accelerometer was used to assess children's 24-h movement behaviours for 7. days, i.e. sleep duration, total SED, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA). Multilevel linear regression models were used to account for the repeated measures nested within participants (there were up to 7 sleep. . PA/SED and PA/SED. . sleep pairings per participant) and schools, and adjusted for covariates. To facilitate interpretation, all sleep and PA/SED variables were standardized. Results showed that the relationship between sleep and PA/SED is bi-directional in this international sample of children. Specifically, for each one standard deviation (SD) unit increase in sleep duration, SED the following day decreased by 0.04 SD units, while LPA and MVPA increased by 0.04 and 0.02 SD units, respectively. Sleep duration decreased by 0.02 SD units and increased by 0.04 SD units for each one SD unit increase in SED and MVPA, respectively. Sleep duration was not affected by changes in LPA. These associations differed across sex and study sites in both directions. However, since the observed effect sizes are subtle, public health initiatives should consider the clinical and practical relevance of these findings. Refereed/Peer-reviewed

Objective In field settings, wrist- and waist-worn accelerometers are typically used to assess sleep characteristics and movement behaviors, respectively. There has been a shift in movement behavior studies to wear accelerometers 24 h/d. Sleep characteristics could be assessed in these studies if sleep algorithms were available for waist-worn accelerometers. The objective of this study was to develop and provide validity data for an algorithm/sleep likelihood score cut-off to estimate sleep efficiency in children using the waist-worn Actical accelerometer. Design Cross-sectional study. Participants Fifty healthy children aged 10-13 years. Measurements Children wore an Actical on their waist and an Actiwatch 2 on their nondominant wrist for 8 nights at home in their normal sleep environment. Participants were randomized into algorithm/sleep likelihood score "development" and "test" groups (n=25 per group). Within the development group, we assessed sleep efficiency with the Actical using the same algorithm that the Actiwatch 2 uses and selected the sleep likelihood score cut-off value that was the most accurate at predicting sleep efficiency at the nightly level compared with the Actiwatch 2. We applied this algorithm and cut-off value to the test group. Results Mean (SD) sleep efficiency estimates for the test group from the Actical and Actiwatch 2 were 89.0% (3.9%) and 88.7% (3.1%), respectively. Bland-Altman plots and absolute difference scores revealed considerable agreement between devices for both nightly and weekly estimates of sleep efficiency. Conclusion A waist-worn Actical accelerometer can accurately predict sleep efficiency in field settings among healthy 10- to 13-year-olds.

Phosphoprotein (P) of the Rabies virus (RABV) is critically required for viral replication and pathogenicity. Here we manipulated infectious cDNA clones of the RABV HEP-Flury to translocate the P gene from its wild-type position 2 to 1, 3, or 4 in gene order, using an approach which left the viral nucleotide sequence unaltered. The recovered viruses were evaluated for the levels of gene expression, growth kinetics in cell culture, lethality in suckling mice and protection of mice. The results showed that viral replication was affected by the absolute value of N protein which was regulated by P protein. Viral lethality in suckling mice was consistent with the ratio of P mRNA in one complete transcription. The protection of mice induced by viruses was related to the antibody titer 5 weeks post-infection which might be regulated by G protein. However, the ability to induce cell apoptosis and viral spread were not only related to the viral replication but also to the ratio of related gene which affected by the gene position. These findings might not only improve the understanding of phenotype of RABV and P gene rearrangement, but also help rabies vaccine candidate construction.

Phosphoprotein (P) of the Rabies virus (RABV) is critically required for viral replication and pathogenicity. Here we manipulated infectious cDNA clones of the RABV HEP-Flury to translocate the P gene from its wild-type position 2 to 1, 3, or 4 in gene order, using an approach which left the viral nucleotide sequence unaltered. The recovered viruses were evaluated for the levels of gene expression, growth kinetics in cell culture, lethality in suckling mice and protection of mice. The results showed that viral replication was affected by the absolute value of N protein which was regulated by P protein. Viral lethality in suckling mice was consistent with the ratio of P mRNA in one complete transcription. The protection of mice induced by viruses was related to the antibody titer 5 weeks post-infection which might be regulated by G protein. However, the ability to induce cell apoptosis and viral spread were not only related to the viral replication but also to the ratio of related gene which affected by the gene position. These findings might not only improve the understanding of phenotype of RABV and P gene rearrangement, but also help rabies vaccine candidate construction.