"You Need to Keep It Going, Mind, Body, and Spirit": Older Adults' Perspectives on Aging in Place in Subsidized Housing.

In the U.S., more than one million older adults with low incomes live in apartment buildings subsidized by the Low-Income Housing Tax Credit. Although this population experiences disproportionate rates of nursing home admission, little is known about residents' perspectives on factors that influence their ability to live independently in these settings. Fifty-eight residents aged 62 and older and eight study partners participated in qualitative interviews about their perspectives on living independently in subsidized housing, including barriers and facilitators. We analyzed transcripts using a hybrid inductive and deductive approach to qualitative thematic analysis. Barriers and facilitators for living independently in subsidized housing related to the influence of the social and physical environment on individuals' experiences of living independently, including factors unique to subsidized housing. Findings suggest how interventions to optimize functional status and promote independence among older adults living in subsidized housing can build on existing strengths of the subsidized housing environment to improve outcomes.

Changes in fitness and fatness in Australian schoolchildren during the summer holidays: fitness lost, fatness regained? A cohort study.

BACKGROUND: Emerging evidence suggests that children's fatness increases and fitness declines at a greater rate during the summer holiday period, compared with the school year. The aim of this study was to compare rates of change in fitness and fatness over the in-term and summer holiday periods among Australian schoolchildren. A secondary aim was to explore whether rates of change differed according to the child's sex, socio-economic status (SES), pubertal status and weight status. METHODS: Children (n = 381) initially in Grade 4 (age 9) were recruited for this 2-year longitudinal study. Fatness (% body fat, BMI z-score, waist-to-height ratio) and fitness (20-m shuttle run and standing broad jump) were measured at the start and end of two consecutive years. Rates of change were calculated for the two in-school periods (Grades 4 and 5) and for the summer holiday period. Rates of change in fatness and fitness between in-school and holiday periods were compared, and differences in rates of change according to sex, socio-economic status, and weight status were explored. RESULTS: During the holidays, percentage body fat increased at a greater rate (annualised rate of change [RoC]: +3.9 vs. Grade 4 and + 4.7 vs. Grade 5), and aerobic fitness declined at a greater rate (RoC - 4.7 vs. Grade 4 and - 4.4 vs. Grade 5), than during the in-school periods. There were no differences in rates of change for BMI z-score, waist-to-height ratio or standing broad jump. Body fatness increased faster in the holidays (relative to the in-school period) in children who are overweight and from low-SES families. Aerobic fitness declined more rapidly in the holidays in children who are overweight. CONCLUSION: This study highlights that during the summer holiday period, children experience greater increases in fatness and declines in fitness, with children who live with low-SES families and are overweight being more affected. The findings suggest the need for targeted interventions during this period to address these negative health trends. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry, identifier ACTRN12618002008202. Retrospectively registered on 14 December 2018.

Parkinson's Disease Action Tremor Detection with Supervised-Leaning Models.

People with Parkinson's Disease (PD) have multiple symptoms, such as freezing of gait (FoG), hand tremors, speech difficulties, and balance issues, in different stages of the disease. Among these symptoms, hand tremors are present across all stages of the disease. PD hand tremors have critical consequences and negatively impact the quality of PD patients' everyday lives. Researchers have proposed a variety of wearable devices to mitigate PD tremors. However, these devices require accurate tremor detection technology to work effectively while the tremor occurs. This paper introduces a PD action tremor detection method to recognize PD tremors from regular activities. We used a dataset from 30 PD patients wearing accelerometers and gyroscope sensors on their wrists. We selected time-domain and frequency-domain hand-crafted features. Also, we compared our hand-crafted features with existing CNN data-driven features, and our features have more specific boundaries in 2-D feature visualization using the t-SNE tool. We fed our features into multiple supervised machine learning models, including Logistic Regression (LR), K-Nearest Neighbours (KNNs), Support Vector Machines (SVMs), and Convolutional Neural Networks (CNNs), for detecting PD action tremors. These models were evaluated with 30 PD patients' data. The performance of all models using our features has more than 90% of F1 scores in five-fold cross-validations and 88% F1 scores in the leave-one-out evaluation. Specifically, Support Vector Machines (SVMs) perform the best in five-fold cross-validation with over 92% F1 scores. SVMs also show the best performance in the leave-one-out evaluation with over 90% F1 scores.

Systematic review and meta-analysis of the effectiveness of chatbots on lifestyle behaviours.

Chatbots (also known as conversational agents and virtual assistants) offer the potential to deliver healthcare in an efficient, appealing and personalised manner. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of chatbot interventions designed to improve physical activity, diet and sleep. Electronic databases were searched for randomised and non-randomised controlled trials, and pre-post trials that evaluated chatbot interventions targeting physical activity, diet and/or sleep, published before 1 September 2022. Outcomes were total physical activity, steps, moderate-to-vigorous physical activity (MVPA), fruit and vegetable consumption, sleep quality and sleep duration. Standardised mean differences (SMD) were calculated to compare intervention effects. Subgroup analyses were conducted to assess chatbot type, intervention type, duration, output and use of artificial intelligence. Risk of bias was assessed using the Effective Public Health Practice Project Quality Assessment tool. Nineteen trials were included. Sample sizes ranged between 25-958, and mean participant age ranged between 9-71 years. Most interventions (n = 15, 79%) targeted physical activity, and most trials had a low-quality rating (n = 14, 74%). Meta-analysis results showed significant effects (all p < 0.05) of chatbots for increasing total physical activity (SMD = 0.28 [95% CI = 0.16, 0.40]), daily steps (SMD = 0.28 [95% CI = 0.17, 0.39]), MVPA (SMD = 0.53 [95% CI = 0.24, 0.83]), fruit and vegetable consumption (SMD = 0.59 [95% CI = 0.25, 0.93]), sleep duration (SMD = 0.44 [95% CI = 0.32, 0.55]) and sleep quality (SMD = 0.50 [95% CI = 0.09, 0.90]). Subgroup analyses showed that text-based, and artificial intelligence chatbots were more efficacious than speech/voice chatbots for fruit and vegetable consumption, and multicomponent interventions were more efficacious than chatbot-only interventions for sleep duration and sleep quality (all p < 0.05). Findings from this systematic review and meta-analysis indicate that chatbot interventions are efficacious for increasing physical activity, fruit and vegetable consumption, sleep duration and sleep quality. Chatbot interventions were efficacious across a range of populations and age groups, with both short- and longer-term interventions, and chatbot only and multicomponent interventions being efficacious.

Children's activity and diet behaviours in the summer holidays versus school year.

BACKGROUND: Evidence shows children gain more weight during the summer holidays versus the school year. OBJECTIVES: To examine within-child differences in activity and diet behaviours during the summer holidays versus the school year. METHODS: Children (mean age 9.4 years; 37% male) wore accelerometers (GENEActiv; n = 133), reported activities (Multimedia Activity Recall for Children and Adolescents; n = 133) and parents reported child diet (n = 133) at five timepoints over 2 years capturing school and summer holiday values. Mixed-effects models were used to compare school and summer holiday behaviours. RESULTS: Children spent less time in moderate- to vigorous-physical activity (-12 min/day; p = 0.001) and sleep (-12 min/day; p < 0.001) and more time sedentary (+27 min/day; p < 0.001) during summer holidays versus the school year. Screentime (+70 min/day; p < 0.001), domestic/social activities (+43 min/day; p = <0.001), self-care (+24 min/day; p < 0.001), passive transport (+22 min/day; p = 0.001) and quiet time (+16 min/day; p = 0.012) were higher during the summer holidays, compensating for less time in school-related activities (-164 min/day; p < 0.001). Diet quality was lower (-4 points; p < 0.001) and children consumed fewer serves of fruit (-0.4 serves; p < 0.001) during the summer holidays versus the school year. CONCLUSIONS: Children are displaying poorer activity and diet behaviours during the summer holidays, which may contribute to accelerated weight gain over the holiday period.

Effectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews.

OBJECTIVE: To synthesise the evidence on the effects of physical activity on symptoms of depression, anxiety and psychological distress in adult populations. DESIGN: Umbrella review. DATA SOURCES: Twelve electronic databases were searched for eligible studies published from inception to 1 January 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of randomised controlled trials designed to increase physical activity in an adult population and that assessed depression, anxiety or psychological distress were eligible. Study selection was undertaken in duplicate by two independent reviewers. RESULTS: Ninety-seven reviews (1039 trials and 128 119 participants) were included. Populations included healthy adults, people with mental health disorders and people with various chronic diseases. Most reviews (n=77) had a critically low A MeaSurement Tool to Assess systematic Reviews score. Physical activity had medium effects on depression (median effect size=-0.43, IQR=-0.66 to -0.27), anxiety (median effect size=-0.42, IQR=-0.66 to -0.26) and psychological distress (effect size=-0.60, 95% CI -0.78 to -0.42), compared with usual care across all populations. The largest benefits were seen in people with depression, HIV and kidney disease, in pregnant and postpartum women, and in healthy individuals. Higher intensity physical activity was associated with greater improvements in symptoms. Effectiveness of physical activity interventions diminished with longer duration interventions. CONCLUSION AND RELEVANCE: Physical activity is highly beneficial for improving symptoms of depression, anxiety and distress across a wide range of adult populations, including the general population, people with diagnosed mental health disorders and people with chronic disease. Physical activity should be a mainstay approach in the management of depression, anxiety and psychological distress. PROSPERO REGISTRATION NUMBER: CRD42021292710.

Parenting Styles and Their Associations With Children's Body Composition, Activity Patterns, Fitness, Diet, Health, and Academic Achievement.

Background: Evidence regarding the impact of parenting style on health and other outcomes is inconsistent and limited by measurement quality and type. This study will examine associations between parenting style and children's objectively assessed activity patterns, body composition, fitness, diet, health, and academic achievement. Methods: Two hundred fifty-five children (mean age: 9.4 years) from Adelaide, Australia, were included. Parenting style (items from Child Rearing Questionnaire and National Longitudinal Survey of Children and Youth to assess Authoritative, Authoritarian, Permissive, Disengaged parenting), diet, and health were proxy-reported by parents. Body composition, fitness, and 24 hour activity patterns were objectively measured, and children reported screen-time. Academic achievement was measured using standardized tests in reading and mathematics. Mixed models were used to regress parenting style against activity patterns, body composition, fitness, diet, health, and academic achievement, adjusted for age, sex, socioeconomic position, and pubertal stage. Results: Children with Disengaged parents had poorer activity patterns: less moderate to vigorous physical activity (standard mean difference [SMD] relative to grand mean = -0.23), light physical activity (SMD = -0.13) and sleep (SMD = -0.18), more sitting (SMD = 0.45), later bedtime (SMD = 0.18), lower overall energy expenditure (SMD = -0.23), and poorer overall self-reported health (SMD = -0.30). Children with Permissive parents had generally better activity patterns (SMD = 0.25-0.32). Children with Authoritative parents were more likely to meet dietary guidelines for fruit intake (SMD = 0.12). There were no associations for Authoritarian parenting style or for academic achievement, body composition, or fitness. Conclusions: Disengaged parenting was detrimental, while Permissive parenting was beneficial for activity patterns. As parenting styles may be malleable, future interventions may target Permissive parenting to improve children's activity patterns. Trial registration: Australia New Zealand Clinical Trials Registry, identifier ACTRN12618002008202. Retrospectively registered on 14 December 2018.

Longitudinal associations between weight status and academic achievement in primary school children.

BACKGROUND: Evidence for longitudinal associations between childhood weight status and academic achievement remains unclear due to considerable heterogeneity in study design, measures of academic achievement and appropriate categorization of weight status. OBJECTIVE: To examine longitudinal associations between childhood weight status (underweight, healthy weight, overweight/obese) and academic achievement in the transition from preschool to primary (elementary) school among Australian school children. METHODS: Data were from the Healthy Active Preschool and Primary Years study. Height and weight, for calculating BMI were measured at baseline (preschool age 3-5 years; 2008/9) and follow-up (primary school age 6-8 years; 2011/12). Academic achievement was measured at age 9 years. RESULTS: No associations between BMI z-score or weight category in the preschool years and later NAPLAN scores were found for boys. For girls, having a higher BMI z-score (B = -13.68, 95%CI: -26.61, -0.76) and being affected by overweight (B = -33.57, 95%CI: -61.50, -5.24) in preschool was associated with lower language scores. Remaining affected by overweight from preschool to primary school was associated with lower numeracy (B = -25.03, 95%CI: -49.74, -0.33), spelling (B = -33.5, 95%CI: -63.43, -3.58), language (B = -37.89, 95%CI: -72.75, -3.03) and total achievement scores (B = -24.24, 95%CI: -44.85, -3.63) among girls. For boys, becoming affected by overweight was associated with lower spelling (B = -38.76, 95%CI: -73.59, -3.93) and total achievement scores (B = -27.70, 95%CI: -54.81, -0.58). CONCLUSIONS: Associations between being affected by overweight/obesity and poorer academic achievement were more pronounced in girls than boys, indicating potentially inequitable impacts of excess weight and highlighting the greater need for intervention among girls. However, stronger study designs are needed to confirm our findings.

Diagnosis and management of type 2 diabetes in children.

ABSTRACT: The incidence of type 2 diabetes in children has risen 4.8% over the past decade, correlating with steadily rising obesity rates in children. Updated guidelines from the American Academy of Pediatrics and the American Diabetes Association encourage early identification and pharmacologic intervention for children with type 2 diabetes. Because of the aggressive disease course in children, comprehensive treatment must include prevention of complications such as diabetic nephropathy and neuropathy as well as management of comorbidities such as cardiovascular disease and dyslipidemia. Because the highest incidence of type 2 diabetes is reported in patients from racial or ethnic minority groups and those of low socioeconomic status, clinicians must work with patients and families to identify socioeconomic disparities that could affect adherence to diabetes management plans and to connect patients with community resources.

A Systematic Review of Factors Associated with Sport Participation among Adolescent Females.

Sport participation provides a direct means to attain health-enhancing physical activity; however, sport participation declines during adolescence, and over 85% of adolescent females fail to meet the recommended 60 min of moderate-vigorous physical activity daily. Given the importance of overcoming barriers to sport and increasing equity in women's sports, the purpose of this systematic review was to identify factors associated with sport participation among adolescent girls and operationalize those factors into theoretical constructs to guide future research. Six databases were systematically searched, and 36 records were included for review. Factors impacting girls' sport participation were categorized as personal, peer, family, socioeconomic, environmental, or other factors. Of these categories, personal factors, including self perceptions and desirable personal outcomes related to sport, were most frequently associated with sport participation. Most research on girls' sport participation lacks theoretical framework, so to aid future studies, this review categorized important participatory factors into the constructs of the theory of planned behavior. Future research would benefit from theory-driven prospective approaches to make clear and consistent predictions about factors impacting sport participation, as well as mixed-method approaches aimed to provide more robust understanding of girls' experiences with and perceptions of factors impacting their participation in sports.

RNA sequencing in a penile cancer cohort: an investigation of biomarkers of cisplatin resistance and potential therapeutic drug targets.

OBJECTIVE: Chemoresistance in distant micrometastatic lesions may account for diminished durable response rates in advanced penile cancer. However, there are limited studies on new therapeutic targets and the identification of biomarkers that predict chemotherapy response in this population. Thus, we examine the expression of candidate biomarkers of cisplatin resistance, ERCC1 and E2F1, and perform next-generation sequencing on the cancer transcriptome in a penile cancer cohort. MATERIALS AND METHODS: In this retrospective cohort study, we identified 71 patients treated for penile squamous cell carcinoma between 2009 and 2019. Immunohistochemistry staining for ERCC1 and E2F1 was performed. H-scores were measured for patient specimens obtained from adjacent normal skin, primary tumor and metastatic lymph node specimens and correlated with RNA expression data obtained through next-generation sequencing. RESULTS: Of the 71 patients identified, 51 and 8 had available surgical specimens for immunohistochemistry and RNA sequencing, respectively. Median H-scores for ERCC1 in adjacent normal skin, primary and metastatic tumors were 17.04, 3.15, and 7.9 respectively compared to E2F1 (43.95, 15.54, 7.9). The median H-score for E2F1 was higher in poorly differentiated primary tumors (24.86) compared to well (7.62) and moderately differentiated (9.55, p = 0.055). Next generation sequencing showed no difference in RNA expression of E2F1 nor ERCC1 between primary tumors and metastatic lesions however did demonstrate elevated RNA expression of genes such as MMP1, and MMP10 in primary tumors compared to adjacent normal skin. CONCLUSION: We identify potential drug targets for metastatic penile cancer through next-generation RNA sequencing.

Associations between meeting 24-hour movement guidelines and academic achievement in Australian primary school-aged children.

BACKGROUND: Few studies have investigated associations between academic achievement and meeting recommendations from the 24-hour (24-h) movement guidelines. The specific guidelines associated with the most benefit academic achievement are unknown. Utilizing both self-report and objective movement data, this study examined associations between academic achievement and meeting individual recommendations and combinations of recommendations from the 24-h movement guidelines (sleep, physical activity, and screen time). METHODS: Data from CheckPoint, a cross-sectional study nested between Waves 6 and 7 of the Longitudinal Study of Australian Children, were used. Movement behaviors were measured using 24-h wrist-worn accelerometry (GENEActiv (Activinsights, Kimbolton, UK)) and were self-reported by children using the Multimedia Activity Recall for Children and Adolescents. Academic achievement was measured using a nationally administered standardized test in literacy and numeracy. Analysis of covariance, with t tests with sequential Bonferroni adjustments, was used to compare academic achievement with all possible combinations of meeting recommendations, adjusting for demographic confounders. Two models were considered: guideline compliance assessed by self-report (n = 1270, mean age = 11.99 years, 52% males) and by accelerometry (for moderate-to-vigorous intensity physical activity (MVPA) and sleep)) and self-report (screen time) in combination (n = 927, mean age = 11.97 years, 52% males). RESULTS: Literacy achievement significantly differed based on self-report (F(7, 1258) = 3.08, p = 0.003) and accelerometer derived (F(7, 915) = 2.40, p = 0.02) guideline compliance. Numeracy achievement significantly differed based on self-report (F(7, 1258) = 2.92, p = 0.005) but not accelerometer derived guideline compliance (F(7, 915) = 0.80, p = 0.58). When assessed by self-report, children who met all guidelines (t(334) = -4.05, p = 0.0001) or met the screen time and sleep guidelines in combination (t(125) = -5.02, p < 0.001) had superior literacy achievement. Meeting the self-report MVPA guideline in any combination was associated with higher numeracy scores (p < 0.05). Post-hoc analyses showed no differences in academic achievement for any category of accelerometer derived guideline compliance. CONCLUSION: The findings suggest that limiting recreational screen time is important for literacy achievement and that encouraging compliance with the MVPA guideline is important for numeracy achievement.

Annual, seasonal, cultural and vacation patterns in sleep, sedentary behaviour and physical activity: a systematic review and meta-analysis.

BACKGROUND: Time spent in daily activities (sleep, sedentary behaviour and physical activity) has important consequences for health and wellbeing. The amount of time spent varies from day to day, yet little is known about the temporal nature of daily activity patterns in adults. The aim of this review is to identify the annual rhythms of daily activity behaviours in healthy adults and explore what temporal factors appear to influence these rhythms. METHODS: Six online databases were searched for cohort studies exploring within-year temporal patterns (e.g. season effects, vacation, cultural festivals) in sleep, sedentary behaviour or physical activity in healthy 18 to 65-year-old adults. Screening, data extraction, and risk of bias scoring were performed in duplicate. Extracted data was presented as mean daily minutes of each activity type, with transformations performed as needed. Where possible, meta-analyses were performed using random effect models to calculate standardised mean differences (SMD). RESULTS: Of the 7009 articles identified, 17 studies were included. Studies were published between 2003 and 2019, representing 14 countries and 1951 participants, addressing variation in daily activities across season (n = 11), Ramadan (n = 4), vacation (n = 1) and daylight savings time transitions (n = 1). Meta-analyses suggested evidence of seasonal variation in activity patterns, with sleep highest in autumn (+ 12 min); sedentary behaviour highest in winter (+ 19 min); light physical activity highest in summer (+ 19 min); and moderate-to-vigorous physical activity highest in summer (+ 2 min) when compared to the yearly mean. These trends were significant for light physical activity in winter (SMD = - 0.03, 95% CI - 0.58 to - 0.01, P = 0.04). Sleep appeared 64 min less during, compared to outside Ramadan (non-significant). Narrative analyses for the impact of vacation and daylight savings suggested that light physical activity is higher during vacation and that sleep increases after the spring daylight savings transition, and decreases after the autumn transition. CONCLUSIONS: Research into temporal patterns in activity behaviours is scarce. Existing evidence suggests that seasonal changes and periodic changes to usual routine, such as observing religious events, may influence activity behaviours across the year. Further research measuring 24-h time use and exploring a wider variety of temporal factors is needed.

VitalCore: Analytics and Support Dashboard for Medical Device Integration.

Medical professionals spend extensive time collecting, validating, reviewing, and analyzing medical device data. These devices use vendor-specific applications with lengthy troubleshooting times, causing extended downtimes where medical professionals have to manually document patient data in the electronic health record (EHR). Manual logging of this data creates delays and leaves it vulnerable to errors, manipulation, and omissions. In this paper, we present VitalCore, a medical device integration platform that supports access to medical device data in real-time. We deploy VitalCore in three applications at Penn Medicine: Medical Device Dashboard, Ventilation Alert, and Anomaly Detector. In the Medical Device Dashboard, we reduced, by up to six times, the amount of time required of medical professionals, clinical engineers, and IT analysts by simplifying the troubleshooting workflow, thus decreasing downtimes and increasing clinical productivity. In Ventilation Alert, we demonstrated the ability to assist medical professionals by alerting them to newly ventilated patients. In Anomaly Detector, we showed that we could predict anomalous patterns in our data with 93% accuracy.

Associations Between 24-Hour Time Use and Academic Achievement in Australian Primary School-Aged Children.

BACKGROUND: Previous research has examined associations between individual activity behaviors and academic achievement. Yet activity behaviors should be analyzed together because they are codependent parts of the 24-hour day. AIMS: This study aims to explore the associations between all daily activity behaviors (sleep, sedentary time, light physical activity [LPA], and moderate-to-vigorous physical activity [MVPA]) and academic achievement using compositional data analysis. METHOD: Participants for this study were drawn from two cohorts: the Australian arm of the cross-sectional International Study of Childhood Obesity, Lifestyle and the Environment (n = 452; mean age 10.7 years (SD = 0.4); 54% female) and CheckPoint (n = 1278; mean age 12 years [SD = 0.4]; 50% female), a cross-sectional study nested between Waves 6 and 7 of the Longitudinal Study of Australian Children. Objective daily activity behavior data (sleep, sedentary time, LPA, and MVPA) were collected using 8-day, 24-hour accelerometry. Academic achievement was assessed using a nationally administered standardized test in literacy (spelling, grammar and punctuation, writing and reading) and numeracy. Compositional models (adjusted for age, sex, socioeconomic position, and pubertal development) regressed academic scores against isometric log ratios of activity behaviors. We used the models to estimate academic achievement for observed daily activity mixes. Estimated outcomes were plotted against time spent in each individual activity domain, and loess curves were fitted. DISCUSSION AND CONCLUSION: In two different cohorts using two different accelerometers, lower LPA was related to better numeracy and literacy and higher sedentary time to better literacy (relative to time spent in other domains). Discussion and conclusion. LPA likely "drains time" from other movement behaviors, which are beneficial for academic achievement.

Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma.

Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.

Discovery and Optimization of wt-RET/KDR-Selective Inhibitors of RETV804M Kinase.

A combination of focused library and virtual screening, hit expansion, and rational design has resulted in the development of a series of inhibitors of RETV804M kinase, the anticipated drug-resistant mutant of RET kinase. These agents do not inhibit the wild type (wt) isoforms of RET or KDR and therefore offer a potential adjunct to RET inhibitors currently undergoing clinical evaluation.

Prospective associations with physiological, psychosocial and educational outcomes of meeting Australian 24-Hour Movement Guidelines for the Early Years.

BACKGROUND: Several countries have released movement guidelines for children under 5 that incorporate guidelines for sleep, physical activity and sedentary behavior. This study examines prospective associations of preschool children's compliance with the 24-Hour Australian movement guidelines (sleep, physical activity, screen time) and physiological, psychosocial and educational outcomes during primary school. METHODS: Data were from the Healthy Active Preschool and Primary Years Study (Melbourne, Australia; n = 471; 3-5 years; 2008/9). Follow-ups occurred at 3 (2011/12; 6-8 years), 6 (2014/15; 9-11 years) and 7 (2016; 10-12 years) years post baseline. Multiple regression models assessed associations between compliance with guidelines at baseline and later outcomes. RESULTS: Children were 4.6 years at baseline (53% boys; 62% high socio-economic families). Most children met physical activity (89%) and sleep (93%) guidelines; 23% met screen-time guidelines; and 20% met all guidelines at baseline. Meeting all of the three guidelines was associated with lower BMI z-scores at 9-11 years of age (b = - 0.26, 95%CI -0.47, - 0.05). Meeting physical activity guidelines was associated with higher total body bone mineral density (b = 0.64, 95%CI 0.15, 1.13), and total body bone mineral content (b = 183.19, 95%CI 69.92, 296.46) at 10-12 years of age. Meeting sleep guidelines was associated with better reading (b = 37.60, 95%CI 6.74, 68.46), spelling (b = 34.95, 95%CI 6.65, 63.25), numeracy (b = 39.09, 95%CI 11.75, 66.44), language (b = 44.31, 95%CI 11.77, 76.85) and writing (b = 25.93, 95%CI 0.30, 51.57) at 8-9 years of age. No associations were evident for compliance with screen-time guidelines or for psychosocial outcomes. CONCLUSIONS: Compliance with different movement behavior guidelines was associated with different outcomes. Strategies to support children in meeting all of the guidelines are warranted to maximize health and educational outcomes. Future research investigating dose-response associations, and potential mechanisms, is necessary.

Life on holidays: study protocol for a 3-year longitudinal study tracking changes in children's fitness and fatness during the in-school versus summer holiday period.

BACKGROUND: Emerging evidence suggests that children become fatter and less fit over the summer holidays but get leaner and fitter during the in-school period. This could be due to differences in diet and time use between these distinct periods. Few studies have tracked diet and time use across the summer holidays. This study will measure rates of change in fatness and fitness of children, initially in Grade 4 (age 9 years) across three successive years and relate these changes to changes in diet and time use between in-school and summer holiday periods. METHODS: Grade 4 Children attending Australian Government, Catholic and Independent schools in the Adelaide metropolitan area will be invited to participate, with the aim of recruiting 300 students in total. Diet will be reported by parents using the Automated Self-Administered 24-h Dietary Assessment Tool. Time use will be measured using 24-h wrist-worn accelerometry (GENEActiv) and self-reported by children using the Multimedia Activity Recall for Children and Adults (e.g. chores, reading, sport). Measurement of diet and time use will occur at the beginning (Term 1) and end (Term 4) of each school year and during the summer holiday period. Fitness (20-m shuttle run and standing broad jump) and fatness (body mass index z-score, waist circumference, %body fat) will be measured at the beginning and end of each school year. Differences in rates of change in fitness and fatness during in-school and summer holiday periods will be calculated using model parameter estimate contrasts from linear mixed effects model. Model parameter estimate contrasts will be used to calculate differences in rates of change in outcomes by socioeconomic position (SEP), sex and weight status. Differences in rates of change of outcomes will be regressed against differences between in-school and summer holiday period diet and time use, using compositional data analysis. Analyses will adjust for age, sex, SEP, parenting style, weight status, and pubertal status, where appropriate. DISCUSSION: Findings from this project may inform new, potent avenues for intervention efforts aimed at addressing childhood fitness and fatness. Interventions focused on the home environment, or alternatively extension of the school environment may be warranted. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry, identifier ACTRN12618002008202 . Retrospectively registered on 14 December 2018.

Process evaluation of a classroom active break (ACTI-BREAK) program for improving academic-related and physical activity outcomes for students in years 3 and 4.

BACKGROUND: Active breaks in the classroom have been shown to be effective for increasing children's physical activity, while simultaneously improving classroom behaviour outcomes. However, there is limited evidence on the feasibility and fidelity of these programs outside of the research context. The purpose of this study was to conduct a process evaluation to explore factors associated with feasibility and fidelity of a classroom active break (ACTI-BREAK) program designed to improve classroom behaviour and physical activity outcomes for children in primary (elementary) school Years 3 and 4. METHODS: Six schools (3 intervention; 3 control) and 374 children (74% response) were included in the ACTI-BREAK pilot cluster randomised controlled trial. The intervention involved teachers implementing 3 × 5-minute moderate-intensity ACTI-BREAKS into their classroom routines, daily. This study focuses on the responses of students (n = 138) and their teachers (n = 7) who participated in the ACTI-BREAK intervention group. Intervention fidelity was assessed by number of ACTI-BREAKS completed per class per day; minutes spent in moderate-intensity physical activity (accelerometry) per ACTI-BREAK; change in physical activity from baseline to mid- and end- intervention. Intervention feasibility was explored through telephone interviews (teachers), questionnaires and focus groups (students), and teacher observations of acute effects on classroom behaviour. Qualitative data were analysed using thematic analyses; acute effects on classroom behaviour and change in physical activity were explored using paired t-tests; questionnaire data were described as frequencies. RESULTS: Teachers implemented two ACTI-BREAKS/day on average, mostly of light-intensity physical activity. Physical activity increased from baseline to mid-, but not baseline to end-intervention; classroom behaviour improved immediately following ACTI-BREAKS. Barriers to implementation included ability for students to return to task and scheduling. Facilitators included ease of implementation, flexible delivery options and student enjoyment. Students were largely satisfied with the program and enjoyed ACTI-BREAKS that incorporated choice, imagination and challenge but did not enjoy ACTI-BREAKS that evoked silliness or were perceived as too difficult and some did not like doing ACTI-BREAKS in the confined space of their classroom. CONCLUSIONS: Results indicated the ACTI-BREAK program was acceptable for students and feasible for teachers, however, some minor modifications in terms of required frequency and intensity could improve fidelity. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ( ACTRN12617000602325 ). Retrospectively registered on 27 April 2017.