A general method for chemogenetic control of peptide function.

Natural or engineered peptides serve important biological functions. A general approach to achieve chemical-dependent activation of short peptides will be valuable for spatial and temporal control of cellular processes. Here we present a pair of chemically activated protein domains (CAPs) for controlling the accessibility of both the N- and C-terminal portion of a peptide. CAPs were developed through directed evolution of an FK506-binding protein. By fusing a peptide to one or both CAPs, the function of the peptide is blocked until a small molecule displaces them from the FK506-binding protein ligand-binding site. We demonstrate that CAPs are generally applicable to a range of short peptides, including a protease cleavage site, a dimerization-inducing heptapeptide, a nuclear localization signal peptide, and an opioid peptide, with a chemical dependence up to 156-fold. We show that the CAPs system can be utilized in cell cultures and multiple organs in living animals.

Regional differences in outcomes with ablation versus drug therapy for atrial fibrillation: Results from the CABANA trial.

BACKGROUND: The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes. METHODS: The examination of treatment effects by geographic region was a prespecified analysis. CABANA enrolled patients from 10 countries, with 1,285 patients at 85 North American (NA) sites and 919 at 41 non-NA sites. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Death and first atrial fibrillation recurrence were secondary endpoints. RESULTS: At least 1 primary endpoint event occurred in 157 patients (12.2%) from NA and 33 (3.6%) from non-NA sites over a median 54.9 and 40.5 months of follow-up, respectively (NA/non-NA adjusted hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.48-3.21, P < .001). In NA patients, 78 events occurred in the ablation and 79 in the drug arm, (HR 0.91, 95% CI 0.66, 1.24) while 11 and 22 events occurred in non-NA patients (HR 0.51, 95% CI 0.25,1.05, interaction P = .154). Death occurred in 53 ablation and 51 drug therapy patients in the NA group (HR 0.96, 95% CI 0.65,1.42) and in 5 ablation and 16 drug therapy patients in the non-NA group (HR 0.32, 95% CI 0.12,0.86, interaction P = .044). Adjusting for baseline regional differences or prognostic risk variables did not account for the regional differences in treatment effects. Atrial fibrillation recurrence was reduced by ablation in both regions (NA: HR 0.54, 95% CI 0.46, 0.63; non-NA: HR 0.44, 95% CI 0.30, 0.64, interaction P = .322). CONCLUSIONS: In CABANA, primary outcome events occurred significantly more often in the NA group but assignment to ablation significantly reduced all-cause mortality in the non-NA group only. These differences were not explained by regional variations in procedure effectiveness, safety, or patient characteristics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0091150; https://clinicaltrials.gov/study/NCT00911508.

Artificial Neural Network Analysis Examining Substance Use Problems Co-Occurring with Anxiety and Depressive Disorders Among Adults Receiving Mental Health Treatment.

Objective: The co-occurrence of anxiety disorders, depressive disorders, and substance use problems was examined. Methods: The Mental Health Client-Level Data dataset was used to conduct logistic regression models and an artificial neural network analysis. Logistic regression analyses were conducted among adults with anxiety (n = 547,473) or depressive disorders (n = 1,610,601) as their primary diagnosis who received treatment in a community mental health center. The artificial neural network analysis was conducted with the entire sample (N = 2,158,074). Results: Approximately 30% of the sample had co-occurring high-risk substance use or substance use disorder. Characteristics including region of treatment receipt, age, education, gender, race and ethnicity, and the presence of co-occurring anxiety and depressive disorders were associated with the co-occurring high-risk substance use or a substance use disorder. Conclusions: Findings from this study highlight the importance of mental health facilities to screen for and provide integrated treatment for co-occurring disorders.

Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial.

BACKGROUND: Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). METHODS: Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models. RESULTS: Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30-1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54-1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75-2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction P value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction P value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age. CONCLUSIONS: We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00911508.

Cost-Effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation: The CABANA Randomized Clinical Trial.

BACKGROUND: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point. METHODS: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D-based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective. RESULTS: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360-$27 170) and the lifetime mean cost difference was $15 516 (95% CI, -$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio <$100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained. CONCLUSIONS: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

Developmental dyscalculia is not associated with atypical brain activation: A univariate fMRI study of arithmetic, magnitude processing, and visuospatial working memory.

Functional neuroimaging serves as a tool to better understand the cerebral correlates of atypical behaviors, such as learning difficulties. While significant advances have been made in characterizing the neural correlates of reading difficulties (developmental dyslexia), comparatively little is known about the neurobiological correlates of mathematical learning difficulties, such as developmental dyscalculia (DD). Furthermore, the available neuroimaging studies of DD are characterized by small sample sizes and variable inclusion criteria, which make it problematic to compare across studies. In addition, studies to date have focused on identifying single deficits in neuronal processing among children with DD (e.g., mental arithmetic), rather than probing differences in brain function across different processing domains that are known to be affected in children with DD. Here, we seek to address the limitations of prior investigations. Specifically, we used functional magnetic resonance imaging (fMRI) to probe brain differences between children with and without persistent DD; 68 children (8-10 years old, 30 with DD) participated in an fMRI study designed to investigate group differences in the functional neuroanatomy associated with commonly reported behavioral deficits in children with DD: basic number processing, mental arithmetic and visuo-spatial working memory (VSWM). Behavioral data revealed that children with DD were less accurate than their typically achieving (TA) peers for the basic number processing and arithmetic tasks. No behavioral differences were found for the tasks measuring VSWM. A pre-registered, whole-brain, voxelwise univariate analysis of the fMRI data from the entire sample of children (DD and TA) revealed areas commonly associated with the three tasks (basic number processing, mental arithmetic, and VSWM). However, the examination of differences in brain activation between children with and without DD revealed no consistent group differences in brain activation. In view of these null results, we ran exploratory, Bayesian analyses on the data to quantify the amount of evidence for no group differences. This analysis provides supporting evidence for no group differences across all three tasks. We present the largest fMRI study comparing children with and without persistent DD to date. We found no group differences in brain activation using univariate, frequentist analyses. Moreover, Bayesian analyses revealed evidence for the null hypothesis of no group differences. These findings contradict previous literature and reveal the need to investigate the neural basis of DD using multivariate and network-based approaches to brain imaging.

Maternal distress and parenting during COVID-19: differential effects related to pre-pandemic distress?

BACKGROUND: Distinguishing whether and how pre-existing characteristics impact maternal responses to adversity is difficult: Does prior well-being decrease the likelihood of encountering stressful experiences? Does it protect against adversity's negative effects? We examine whether the interaction between relatively uniformly experienced adversity (due to COVID-19 experience) and individual variation in pre-existing (i.e., pre-pandemic onset) distress predicted mothers' pandemic levels of distress and insensitive caregiving within a country reporting low COVID-19 death rates, and strict nationwide regulations. METHOD: Fifty-one Singaporean mothers and their preschool-aged children provided data across two waves. Pre- pandemic onset maternal distress (i.e., psychological distress, anxiety, and parenting stress) was captured via self-reports and maternal sensitivity was coded from videos. Measures were repeated after the pandemic's onset along with questionnaires concerning perceived COVID-19 adversity (e.g., COVID-19's impact upon stress caring for children, housework, job demands, etc.) and pandemic-related objective experiences (e.g., income, COVID-19 diagnoses, etc.). Regression analyses (SPSS v28) considered pre-pandemic onset maternal distress, COVID-19 stress, and their interaction upon post-pandemic onset maternal distress. Models were re-run with appropriate covariates (e.g., objective experience) when significant findings were observed. To rule out alternative models, follow up analyses (PROCESS Model) considered whether COVID-19 stress mediated pre- and post-pandemic onset associations. Models involving maternal sensitivity followed a similar data analytic plan. RESULTS: Pre-pandemic maternal distress moderated the association between COVID-19 perceived stress and pandemic levels of maternal distress (ß = 0.22, p < 0.01) but not pandemic assessed maternal sensitivity. Perceived COVID-19 stress significantly contributed to post-pandemic onset maternal distress for mothers with pre-pandemic onset distress scores above (ß = 0.30, p = 0.05), but not below (ß = 0.25, p = 0.24), the median. Objective COVID-19 adversity did not account for findings. Post-hoc analyses did not suggest mediation via COVID-19 stress from pre-pandemic to pandemic maternal distress. CONCLUSIONS: Pre-existing risk may interact with subsequent perceptions of adversity to impact well-being. In combination with existing research, this small study suggests prevention programs should focus upon managing concurrent mental health and may highlight the importance of enhanced screening and proactive coping programs for people entering high stress fields and/or phases of life.

Heterogeneity in children at risk of math learning difficulties.

This study recruited 428 Singaporean children at risk of math learning difficulties (MLD; Mage  = 83.9 months, SDage  = 4.35 months; 41% female). Using a factor mixture model that considered both quantitative and qualitative differences in math ability, two qualitatively different groups were identified: one with generalized difficulties across different math skills and the other with more focal difficulties in arithmetic fluency. Reading, working memory capacity, and numeracy (number line estimation skills and numerical discrimination) uniquely explained group membership. Children within each group differed in the extent of difficulties they exhibited, with numeracy variables differentially contributing to math ability in each group. Findings speak against a dimensional view of MLD and underscore the conceptual limitations of using basic numeracy performance to profile learning difficulties.

How do distracting events influence children's arithmetic performance?

To understand how distraction influences children's arithmetic performance, we examined effects of irrelevant sounds on children's performance while they solve arithmetic problems. Third and fifth graders were asked to verify true/false, one-digit addition problems (e.g., 9 + 4 = 12. True? False?) under silence and sound conditions. The sounds began when the problems started to appear on the screen (Experiment 1; N = 76) or slightly after (Experiment 2; N = 92) and continued until participants responded. The results showed that (a) children solved arithmetic problems more quickly in the sound condition than in the silence condition when the sounds started with problem display (phasic arousal effects); (b) children were slower on the arithmetic problem verification task when the sounds was played slightly after the problems started to appear on the screen (distraction effects); (c) phasic arousal effects were found only in third graders, whereas distraction effects were found in both grades, although their magnitudes were smaller in fifth graders; (d) distraction effects increased with increasing latencies in third graders but did not change across the entire latency distribution in fifth graders; and (e) distraction effects on current trials were smaller after sound trials than after silence trials in both age groups (sequential modulations of distraction effects). These findings have important implications for furthering our understanding of effects of irrelevant sounds on arithmetic performance as well as cognitive processes involved in children's arithmetic.

Implementing a Child Mental Health Intervention in Child Welfare Services: Stakeholder Perspectives on Feasibility.

This pilot study integrated quantitative and qualitative data to examine the feasibility of implementing a modified version of a multiple family group behavioral parent training intervention (The 4Rs and 2Ss for Strengthening Families Program [4Rs and 2Ss]) in child welfare (CW) placement prevention services, from the perspectives of participating caregivers (n = 12) and CW staff (n = 12; i.e., 6 caseworkers, 4 supervisors, and 2 administrators). Quantitative surveys were administered to caregivers and CW staff followed by semi-structured interviews to examine the feasibility of implementing the modified 4Rs and 2Ss program, as well as factors impacting feasibility. Results indicated that quantitative benchmarks for high feasibility were met in all assessed areas (e.g., family recruitment, caseworker fidelity ratings, CW staff feasibility ratings) except for family attendance, which was markedly lower than desired. Factors facilitating feasibility included agency and research support, intervention ease-of-use, perceived benefits to existing CW practice, as well as logistical support (e.g., food, transportation, childcare) promoting attendance. Factors hindering feasibility included conflicts between research-based eligibility criteria and existing client population demographics, research-related processes resulting in delays, CW staff role conflicts, added workload burden, complex family issues, and power differentials inherent to CW services which complicated families' voluntary participation.

Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure: Results From the CABANA Trial.

BACKGROUND: In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). METHODS: The CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial's primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. RESULTS: Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 [95% CI, 0.41-0.99]) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 [95% CI, 0.33-0.96]) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 [95% CI, 0.42-0.74]). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5-7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was -2.0 points, favoring ablation (95% CI, -2.9 to -1.2). CONCLUSIONS: In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508; Unique identifier: NCT0091150.

Myocardial Viability and Long-Term Outcomes in Ischemic Cardiomyopathy.

BACKGROUND: The role of assessment of myocardial viability in identifying patients with ischemic cardiomyopathy who might benefit from surgical revascularization remains controversial. Furthermore, although improvement in left ventricular function is one of the goals of revascularization, its relationship to subsequent outcomes is unclear. METHODS: Among 601 patients who had coronary artery disease that was amenable to coronary-artery bypass grafting (CABG) and who had a left ventricular ejection fraction of 35% or lower, we prospectively assessed myocardial viability using single-photon-emission computed tomography, dobutamine echocardiography, or both. Patients were randomly assigned to undergo CABG and receive medical therapy or to receive medical therapy alone. Left ventricular ejection fraction was measured at baseline and after 4 months of follow-up in 318 patients. The primary end point was death from any cause. The median duration of follow-up was 10.4 years. RESULTS: CABG plus medical therapy was associated with a lower incidence of death from any cause than medical therapy alone (182 deaths among 298 patients in the CABG group vs. 209 deaths among 303 patients in the medical-therapy group; adjusted hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.90). However, no significant interaction was observed between the presence or absence of myocardial viability and the beneficial effect of CABG plus medical therapy over medical therapy alone (P = 0.34 for interaction). An increase in left ventricular ejection fraction was observed only among patients with myocardial viability, irrespective of treatment assignment. There was no association between changes in left ventricular ejection fraction and subsequent death. CONCLUSIONS: The findings of this study do not support the concept that myocardial viability is associated with a long-term benefit of CABG in patients with ischemic cardiomyopathy. The presence of viable myocardium was associated with improvement in left ventricular systolic function, irrespective of treatment, but such improvement was not related to long-term survival. (Funded by the National Institutes of Health; STICH ClinicalTrials.gov number, NCT00023595.).

Influence of atrial fibrillation type on outcomes of ablation vs. drug therapy: results from CABANA.

AIMS: Influence of atrial fibrillation (AF) type on outcomes seen with catheter ablation vs. drug therapy is incompletely understood. This study assesses the impact of AF type on treatment outcomes in the Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA). METHODS AND RESULTS: CABANA randomized 2204 patients ≥65 years old or <65 with at least one risk factor for stroke to catheter ablation or drug therapy. Of these, 946 (42.9%) had paroxysmal AF (PAF), 1042 (47.3%) had persistent AF (PersAF), and 215 (9.8%) had long-standing persistent AF (LSPAF) at baseline. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Symptoms were measured with the Mayo AF-Specific Symptom Inventory (MAFSI), and quality of life was measured with the Atrial Fibrillation Effect on Quality of Life (AFEQT). Comparisons are reported by intention to treat. Compared with drug therapy alone, catheter ablation produced a 19% relative risk reduction in the primary endpoint for PAF {adjusted hazard ratio [aHR]: 0.81 [95% confidence interval (CI): 0.50, 1.30]}, and a 17% relative reduction for PersAF (aHR: 0.83, 95% CI: 0.56, 1.22). For LSPAF, the ablation relative effect was a 7% reduction (aHR: 0.93, 95% CI: 0.36, 2.44). Ablation was more effective than drug therapy at reducing first AF recurrence in all AF types: by 51% for PAF (aHR: 0.49, 95% CI: 0.39, 0.62), by 47% for PersAF (aHR: 0.53, 95% CI: 0.43,0.65), and by 36% for LSPAF (aHR 0.64, 95% CI 0.41,1.00). Ablation was associated with greater improvement in symptoms, with the mean difference between groups in the MAFSI frequency score favouring ablation over 5 years of follow-up in all subgroups: PAF had a clinically significant -1.9-point difference (95% CI: -1.2 to -2.6); PersAF a -0.9 difference (95% CI: -0.2 to -1.6); LSPAF a clinically significant difference of -1.6 points (95% CI: -0.1 to -3.1). Ablation was also associated with greater improvement in quality of life in all subgroups, with the AFEQT overall score in PAF patients showing a clinically significant 5.3-point improvement (95% CI: 3.3 to 7.3) over drug therapy alone over 5 years of follow-up, PersAF a 1.7-point difference (95% CI: 0.0 to 3.7), and LSPAF a 3.1-point difference (95% CI: -1.6 to 7.8). CONCLUSION: Prognostic treatment effects of catheter ablation compared with drug therapy on the primary and major secondary clinical endpoints did not differ consequentially by AF subtype. With regard to decreases in AF recurrence and improving quality of life, ablation was more effective than drug therapy in all three AF type subgroups. CLINICALTRIALS.GOV IDENTIFIER: NCT00911508.

Maternal education and siblings: Agents of cognitive development in kindergarten.

In this study (n = 1000, Mage at K1entry  = 53.4 months, SD = 3.4; 53% females), we investigated the contributions of the family socioeconomic status (SES; maternal education and an income-related measure) and number and age of siblings to the development of children's math, reading, and working memory (WM) updating skills over the kindergarten years. Results from a multivariate multilevel growth curve model showed that children from more disadvantaged SES backgrounds already had a multifaceted developmental lag at kindergarten entry. Maternal education was the aspect of SES that more clearly affected the child's cognitive development; the mother's education predicted children's math, reading, and WM-updating skills at kindergarten entry as well as the rate of development of reading skills over the kindergarten years. Independently of SES status, children with more siblings also showed poorer reading and math skills than those in one-child families at kindergarten entry. We also found that both older and younger siblings affected, negatively, children's reading skills before they attended kindergarten-which suggests that the development of reading skills is more responsive to environmental factors during the first years than other aspects of the child development. The findings underscore the independent role of siblings upon entry to kindergarten, and the enduring role of maternal education even after children are exposed to formal schooling.

Weekday breakfast habits and mood at the start of the school morning.

BACKGROUND: Good nutrition, regular physical activity, and adequate sleep are important for promoting health. However, it is not well characterized how these lifestyle behaviours are associated with mood at the start of school days. AIM: To identify the weekday health-related behaviours (breakfast intake, physical activity, and sleep) of Singaporean adolescents and explore their associations with mood at the beginning of the school morning. METHODS: 365 adolescents (52.3% boys, 47.7% girls) aged 14-19 years (M = 16.9, SD = 1.3 years) completed a survey set on breakfast habits, physical activity participation, sleep duration, and mood. RESULTS: More than one-third (38.6%) of participants never (15.0%) or irregularly (23.6%) consumed breakfast on weekdays. Adolescents consuming breakfast irregularly reported significantly higher negative mood scores than regular breakfast consumers (p = .002; d = .404). Almost two-thirds (64.1%) of adolescents did <60 min of moderate-to-vigorous physical activity (MVPA) on weekdays and reported lower positive morning mood scores than those who ≥60 min of MVPA (p = .014; d = .284). Although most (88.3%) adolescents slept <8 h each night, sleep duration was not related to either positive mood or negative mood. CONCLUSION: The present study suggests that eating breakfast on a regular basis and completing for ≥60 min of weekday MVPA are useful behaviours to start school days in a better mood. Parents and health educators should recognise the importance of establishing these habits and support students by instigating practical approaches so they can achieve a regular breakfast intake and physical activity engagement.

A systematic review of primary school teachers' experiences with digital technologies curricula.

Many countries around the world have now introduced Digital Technology concepts and pedagogical practices to their primary school curricula to ensure students develop the understanding, competences and values that will enable them to contribute to and benefit from their future labour market and society. This study aimed to explore teachers' experiences with these curricula in order to understand how teachers can be supported to raise their implementation efforts. An analysis of twenty-three studies across eleven countries was undertaken and found there was a lack of consensus of an appropriate age and approach to introducing Digital Technology concepts within primary schools. Teachers' Digital Technology self-efficacy, Digital Technology self-esteem/ Digital Technology confidence was seen to greatly influence their implementation, and many challenges to implementation were discussed. Professional Learning and Development was raised as a solution to boost teachers' confidence and overcome common implementation barriers.

Socioeconomic status, home mathematics environment and math achievement in kindergarten: A mediation analysis.

Growing evidence suggests that parents' practices contribute to their children's cognitive development and that such practices may reflect SES disparities. This study investigated longitudinal interrelations between home mathematics environment (HME), children's math achievement, and two facets of SES (mother's educational attainment and household income-subsidy status) during the first year in kindergarten (n = 500 children; Mage at T1 = 57.3 months, SD = 3.8). Results revealed that these facets of SES operated through different mechanisms in kindergarten-the association between mothers' education and math growth at the end of K1 is fully mediated by HME and children's baseline math knowledge. Furthermore, only home math activities that explicitly supported the understanding of addition and subtraction contributed to children's math growth independently of SES background. The pattern of longitudinal associations suggests that the provision of home math activities may reflect children's mathematical abilities rather than SES disparities.

An Exploratory Study of the Prosecution of Fatal Child Maltreatment: Criminal Charges Filed Against Presumed Perpetrators in the United States in 2017.

In the United States child maltreatment fatalities (CMFs) do not usually meet the standard for manslaughter or murder, resulting in convictions of lesser crimes and little jail time. This exploratory study examined the charges brought against suspected CMF perpetrators in 2017. Univariate and bivariate analyses were conducted using data obtained from the Nexis Uni newspaper database, that has over 40,000 high quality media sources, for the year 2017. We found that the most frequently used charges were endangering the welfare of a child and murder, the former of which was more related to neglect-deaths and the latter to physical abuse-deaths. There was no difference between charges for male and female perpetrators. Practical implications for research, policy, and practice are discussed.

Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial.

AIMS: We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. METHODS AND RESULTS: The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke. CONCLUSIONS: Echocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.

Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study). METHODS: The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.