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Background Machine learning tools that semi-automate data extraction may create efficiencies in systematic review production. We evaluated a machine learning and text mining tool’s ability to (a) automatically extract data elements from randomized trials, and (b) save time compared with manual extraction and verification. Methods For 75 randomized trials, we manually extracted and verified data for 21 data elements. We uploaded the randomized trials to an online machine learning and text mining tool, and quantified performance by evaluating its ability to identify the reporting of data elements (reported or not reported), and the relevance of the extracted sentences, fragments, and overall solutions. For each randomized trial, we measured the time to complete manual extraction and verification, and to review and amend the data extracted by the tool. We calculated the median (interquartile range [IQR]) time for manual and semi-automated data extraction, and overall time savings. Results The tool identified the reporting (reported or not reported) of data elements with median (IQR) 91% (75% to 99%) accuracy. Among the top five sentences for each data element at least one sentence was relevant in a median (IQR) 88% (83% to 99%) of cases. Among a median (IQR) 90% (86% to 97%) of relevant sentences, pertinent fragments had been highlighted by the tool; exact matches were unreliable (median (IQR) 52% [33% to 73%]). A median 48% of solutions were fully correct, but performance varied greatly across data elements (IQR 21% to 71%). Using ExaCT to assist the first reviewer resulted in a modest time savings compared with manual extraction by a single reviewer (17.9 vs. 21.6 h total extraction time across 75 randomized trials). Conclusions Using ExaCT to assist with data extraction resulted in modest gains in efficiency compared with manual extraction. The tool was reliable for identifying the reporting of most data elements. The tool’s ability to identify at least one relevant sentence and highlight pertinent fragments was generally good, but changes to sentence selection and/or highlighting were often required. Protocol https://doi.org/10.7939/DVN/RQPJKS

Background Reliance on P-value of significance in clinical trials is a source of debate because of misconceptions and misinterpretations associated with it. Bayesian methods are suggested as an alternative approach. As randomized-controlled trials (RCTs) are essential in generating research evidence, we investigated the change in the use of P-values and Bayesian analysis and the clustering of P-values at key significance levels in child health RCTs published in 2007 and 2017. Methods We searched Cochrane Central Register of Controlled Trials to identify random samples of child health RCTs published in 2007 (n = 300) and 2017 (n = 300). Data on trial characteristics and analytic approaches were extracted. We analyzed the 600 RCTs using the frequentist and Bayesian methods. The change in the proportion of trials reporting P-values and Bayesian analyses was assessed using Pearson/Fisher Exact tests and non-informative Dirichlet priors. Results Of 600 RCTs, 535 (89%) used frequentist methods only versus 65 (11%) that included some Bayesian methods. Only 2 of the 65 trials used Bayesian inferential statistics. The use of frequentist methods decreased from (273, 91% to 262, 87%) while the inclusion of Bayesian analysis slightly increased from (27, 9% to 38, 13%) between 2007 and 2017. Although most RCTs were from Europe (172, 29%) and North America (133, 22%), the increase in proportion of trials by continent was most in Asia (mean difference (MD) = 0.14, 95% credible interval (CI) 0.08–0.20) with posterior probability (PP) of 1.00. Parallel (487, 81.2%) and cluster (58, 9.7%) RCTs were the most common RCT types but the increase in cluster RCT (0.06, 95%CI 0.02–0.11, PP = 0.99) was more than any other RCT types over 10 years. We found clustering of P-values at the significance level of 0.05 (437, 72.8%), which increased between 2007 (209, 69.7%) and 2017 (228, 76%). The smallest P-value reported in this review was 0.0001 (1, 0.2%). Conclusions The statistical framework in child health RCTs has not changed from the frequentist methods that is based on P-values with an unexplained clustering at the significance level of 0.05. Bayesian methods may increase the confidence in interpretation of results of RCTs

Objective:Increasing evidence links unhealthy food environments with diet quality and overweight/obesity. Recent evidence has demonstrated that relative food environment measures outperform absolute measures. Few studies have examined the interplay between these two measures. We examined the separate and combined effects of the absolute and relative densities of unhealthy food outlets within 1600 m buffers around elementary schools on children’s diet- and weight-related outcomes.Design:This is a cross-sectional study of 812 children from thirty-nine schools. The Youth Healthy Eating Index (Y-HEI) and daily vegetables and fruit servings were derived from the Harvard Food Frequency Questionnaire for Children and Youth. Measured heights and weights determined BMI Z-scores. Food outlets were ranked as healthy, somewhat healthy and unhealthy according to provincial paediatric nutrition guidelines. Multilevel mixed-effects regression models were used to assess the effect of absolute (number) and relative (proportion) densities of unhealthy food outlets within 1600 m around schools on diet quality and weight status.Setting:Two urban centres in the province of Alberta, Canada.Participants:Grade 5 students (10–11 years).Results:For children attending schools with a higher absolute number (36+) of unhealthy food outlets within 1600 m, every 10 % increase in the proportion of unhealthy food outlets was associated with 4·1 lower Y-HEI score and 0·9 fewer daily vegetables and fruit.Conclusions:Children exposed to a higher relative density of unhealthy food outlets around a school had lower diet quality, specifically in areas where the absolute density of unhealthy food outlets was also high.

Capturing socioeconomic inequalities in relation to chronic disease is challenging since socioeconomic status (SES) encompasses many aspects. We constructed a comprehensive individual-level SES index based on a broad set of social and demographic indicators (gender, education, income adequacy, occupational prestige, employment status) and examined its relationship with smoking, a leading chronic disease risk factor. Analyses were based on baseline data from 17,371 participants of Alberta’s Tomorrow Project (ATP), a prospective cohort of adults aged 35–69 years with no prior personal history of cancer. To construct the SES index, we used principal component analysis (PCA) and to illustrate its utility, we examined the association with smoking intensity and smoking history using multiple regression models, adjusted for age and gender. Two components were retained from PCA, which explained 61% of the variation. The SES index was best aligned with educational attainment and occupational prestige, and to a lesser extent, with income adequacy. In the multiple regression analysis, the SES index was negatively associated with smoking intensity (p < 0.001). Study findings highlight the potential of using individual-level SES indices constructed from a broad set of social and demographic indicators in epidemiological research.

Emerging evidence suggests that the COVID-19 pandemic and associated public health measures, including lockdowns and school closures, have been negatively affecting school-aged children’s psychological wellbeing. To identify supports required to mitigate the negative impacts of the COVID-19 pandemic, we gathered in-depth information on school-aged children’s and parents’ lived experiences of COVID-19 and perceptions of its impact on psychological wellbeing in grade 4–6 students in Canada. In this qualitative study, we conducted telephone-based semi-structured interviews with parents (n = 15) and their children (n = 16) from six schools in small and mid-sized northern prairie communities in Canada. Interviews were analyzed through thematic analysis. Three interrelated themes have emerged. First, the start of COVID-19 brought sudden and stressful changes to children’s lives. Second, disruptions to daily life led to feelings of boredom and lack of purpose. Third, limited opportunities for social interaction led to loneliness and an increase in screen time to seek social connection with peers. Results underscore the need for resilience building and the promotion of positive coping strategies to help school-aged children thrive in the event of future health crises or natural disasters.

Background: There is an unresolved debate about the reliability of the interpretation of P-value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P-value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. Methods: We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. Discussion: We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P-value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P-values of significance, if observed, will be reported. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods.Systematic review registration: Open Science Framework https://osf.io/aj2df

Background There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. Methods We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P values of significance, if observed, will be reported. Discussion This review will present the difference in the proportion of trials that reported on P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. The implications for future clinical research will be discussed and this research work will be published in a peer-reviewed journal. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods. Systematic review registration Open Science Framework https://osf.io/aj2df

Introduction The National Advisory Committee on Immunization (NACI) makes recommendations for vaccines in Canada. To inform considerations for equity when making recommendations, the NACI Secretariat developed a matrix of factors that may influence vaccine equity. To inform the matrix we mapped the evidence for P2ROGRESS And Other factors potentially associated with unequal levels of illness or death from vaccine-preventable diseases (VPDs) and systematically reviewed the evidence for interventions aimed at reducing inequities. Methods In October 2019 we searched Medline, Embase, and CINAHL. Two reviewers agreed on the included studies. Our primary outcomes were VPD-related hospitalizations and deaths. Secondary outcomes were differential vaccine access, and exposure, susceptibility, severity, and consequences of VPDs. Two reviewers appraised the certainty of evidence. We mapped the evidence for P2ROGRESS And Other factors and summarized the findings descriptively. We summarized the interventions narratively. Results We identified 413 studies reporting on P2ROGRESS And Other factors. The most commonly investigated factors included age (n = 374, 89%), pre-existing conditions (n = 179, 42%), and gender identity or sex (n = 144, 34%). We identified 2 trials investigating the effects of interventions. One (n = 1249) provided very low certainty evidence that staff vaccination policies may reduce hospitalizations and deaths from influenza among private care home residents. The other (n not reported) provided very low certainty evidence that universal vaccination by nurses in clinics may reduce hospitalizations for rotavirus gastroenteritis compared with vaccination by physicians or no intervention. Conclusions There is a large body of studies reporting on hospitalizations and deaths from VPDs stratified by P2ROGRESS And Other factors. We found only two trials examining the effects of interventions on hospitalization for or mortality from VPDs. This review has been helpful to NACI and will be helpful to similar organizations aiming to systematically identify and target health inequities through the development of vaccine program recommendations.

Separation of duplicated spindle poles is the first step in forming the mitotic spindle. Kinesin-5 crosslinks and slides anti-parallel microtubules (MTs), but it is unclear how these two activities contribute to the first steps in spindle formation. In this study, we report that in monopolar spindles, the duplicated spindle poles snap apart in a fast and irreversible step that produces a nascent bipolar spindle. Using mutations in Kinesin-5 that inhibit microtubule sliding, we show that the fast, irreversible pole separation is primarily driven by microtubule crosslinking. Electron tomography revealed microtubule pairs in monopolar spindles have short overlaps that intersect at high angles and are unsuited for ensemble Kinesin-5 sliding. However, maximal extension of a subset of anti-parallel microtubule pairs approaches the length of nascent bipolar spindles and is consistent with a Kinesin-5 crosslinking-driven transition. Nonetheless, microtubule sliding by Kinesin-5 contributes to stabilizing the nascent spindle and setting its stereotyped equilibrium length.

SUMMARYGRAPHICAL ABSTRACTSeparation of duplicated spindle poles is the first step in forming the mitotic spindle. Kinesin-5 crosslinks and slides anti-parallel microtubules, but it is unclear how these two activities contribute to the first steps in spindle formation. In this study we report that in monopolar spindles, the duplicated spindle poles snap apart in a fast and irreversible step that produces a nascent bipolar spindle. Using mutations in Kinesin-5 that inhibit microtubule sliding, we show crosslinking alone drives the fast, irreversible pole separation. Electron tomography revealed microtubule pairs in monopolar spindles have short overlaps that intersect at high angles and are unsuited for ensemble Kinesin-5 sliding. However, maximal extension of a subset of microtubule pairs approaches the length of nascent bipolar spindles and is consistent with a Kinesin-5 crosslinking driven transition. Finally, stochastic microtubule sliding by Kinesin-5 stabilizes the nascent spindle and sets a stereotyped equilibrium length.

Summary: The segregation of chromosomes is a critical step during cell division. This process is driven by the elongation of spindle microtubules and is tightly regulated by checkpoint mechanisms. It is unknown whether microtubules affect checkpoint responses as passive contributors or active regulators of the process. We show here that interphase microtubules are essential to temporally restrict the effects of DNA replication stress to S phase in Saccharomyces cerevisiae. Tubulin mutants hypersensitive to DNA damage experience a strong but delayed mitotic checkpoint arrest after exposure to genotoxic stress in S phase. This untimely arrest is dependent on the Aurora B kinase but, surprisingly, not on the DNA damage checkpoint. Impaired microtubule-kinetochore interaction is the apparent cause for this unusual phenotype. Collectively, our results reveal that core components of microtubules potentiate the detection of DNA lesions created in S phase, thereby suppressing untimely activation of mitotic checkpoints after DNA replication stress. : DNA replication stress is detected in S phase by a dedicated checkpoint machinery that ensures cells do not enter mitosis with damaged chromosomes. Laflamme et al. found that microtubules limit the effects of replication stress to S phase by modulating the levels of tension at sister kinetochores of replicated chromatids. Keywords: microtubules, Aurora B kinase, replication stress, DNA damage, kinetochore, mitosis, checkpoint

A critical step in mitosis is the formation of a functional bipolar spindle, a complex molecular machine responsible for accurate chromosome segregation between daughter cells at the end of cell division. The ability of force-generating molecular motors to cross-link and slide anti-parallel microtubules has been implicated in formation of a bi-polar spindle. In the simple eukaryotic spindle of yeast, kinesin-5 (Cin8) and kinesin-14 (Kar3) has long been thought to drive the initial separation of duplicated spindle poles. Here we show that the spindle rapidly and irreversibly transitions from a compacted to extended state, and suggest that the underlying process is powered by the cross-linked bent microtubules as a loaded spring.Using 3-D electron tomography, we model and characterize the initial state of this process, revealing the microtubule overlap architecture on which the Kinesin-5 motor proteins bind. Combining in-vivo imaging with fluorescence labeling of spindle poles and tracking algorithms, we quantify transition characteristics such as spindle pole velocity. Critically, we measure the velocity of pole separation during this transition to be greater than that expected microtubule sliding via Cin8 or Kar3. We observed that the velocity of pole separation in a non-sliding but microtubule cross-linking Cin8 mutant (Cin8-3, Sablin et al., 1996) also supports an alternate process to motor driven anti-parallel sliding. Further characterization of the pole-separation mechanisms will clarify how this basic yet essential aspect of eukaryotic life is accurately completed.