TINNiK: Inference of the Tree of Blobs of a Species Network Under the Coalescent.

The tree of blobs of a species network shows only the tree-like aspects of relationships of taxa on a network, omitting information on network substructures where hybridization or other types of lateral transfer of genetic information occur. By isolating such regions of a network, inference of the tree of blobs can serve as a starting point for a more detailed investigation, or indicate the limit of what may be inferrable without additional assumptions. Building on our theoretical work on the identifiability of the tree of blobs from gene quartet distributions under the Network Multispecies Coalescent model, we develop an algorithm, TINNiK, for statistically consistent tree of blobs inference. We provide examples of its application to both simulated and empirical datasets, utilizing an implementation in the MSCquartets 2.0 R package.

Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants. Our gene-level collapsing analysis revealed that rare damaging variants in SAMHD1 as well as genes in the DNA damage response pathway ( BRCA2 , ATM and CHEK2 ) are associated with the risk of overall prostate cancer. We also found that rare damaging variants in AOX1 and BRCA2 were associated with increased severity of prostate cancer in a case-only analysis of aggressive versus non-aggressive prostate cancer. At the single-variant level, we found rare non-synonymous variants in three genes ( HOXB13 , CHEK2 , BIK ) significantly associated with increased risk of overall prostate cancer and in four genes ( ANO7 , SPDL1 , AR , TERT ) with decreased risk. Altogether, this study provides deeper insights into the genetic architecture and biological basis of prostate cancer risk and severity.

Impact of the inaccessible genome on genotype imputation and genome-wide association studies.

Genotype imputation is widely used in genome-wide association studies (GWAS). However, both the genotyping chips and imputation reference panels are dependent on next-generation sequencing (NGS). Due to the nature of NGS, some regions of the genome are inaccessible to sequencing. To date, there has been no complete evaluation of these regions and their impact on the identification of associations in GWAS remains unclear. In this study, we systematically assess the extent to which variants in inaccessible regions are underrepresented on genotyping chips and imputation reference panels, in GWAS results and in variant databases. We also determine the proportion of genes located in inaccessible regions and compare the results across variant masks defined by the 1000 Genomes Project and the TOPMed program. Overall, fewer variants were observed in inaccessible regions in all categories analyzed. Depending on the mask used and normalized for region size, only 4%-17% of the genotyped variants are located in inaccessible regions and 52 to 581 genes were almost completely inaccessible. From the Cooperative Health Research in South Tyrol (CHRIS) study, we present a case study of an association located in an inaccessible region that is driven by genotyped variants and cannot be reproduced by imputation in GRCh37. We conclude that genotyping, NGS, genotype imputation and downstream analyses such as GWAS and fine mapping are systematically biased in inaccessible regions, due to missed variants and spurious associations. To help researchers assess gene and variant accessibility, we provide an online application (https://gab.gm.eurac.edu).

Indications and outcomes of transjugular intrahepatic portosystemic shunt insertion in two regional Australian hepatology centres.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings. AIMS: The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres. METHODS: Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed. RESULTS: Forty-eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46-65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre- and post-TIPS were 10 (IQR: 4.5-16) and 2 (IQR: 0-4) respectively (P < 0.001). There were no procedure-related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre-TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post-TIPS (P < 0.001). CONCLUSIONS: TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting.

From little things big things grow: enhancement of an acoustic telemetry network to monitor broad-scale movements of marine species along Australia's east coast.

BACKGROUND: Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. METHODS: Since 2007, the Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. RESULTS: The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore "redundancy" is a critical consideration when designing this type of array. CONCLUSION: Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

Gamification to Promote Physical Activity in Youth and Mothers With Obesity.

PURPOSE: Physical inactivity and sugar-sweetened beverage (SSB) consumption are associated with obesity. Gamification and self-monitoring to promote physical activity in youth is unknown, but evidence of effectiveness is present in adults. This study examined the effects of a gamification intervention on increased steps per day among parent-adolescent dyads with obesity compared with digital self-monitoring and if self-monitored SSB intake differed between these arms. METHODS: Youth ages 10-16 years and their mothers (N = 39 pairs), both with obesity, were randomized to a self-monitoring (N = 18) or a self-monitoring plus gamification arm (N = 21) for 9 weeks. The step goal was set and incrementally increased each week and was measured with Fitbit devices. Mixed effects linear regression examined changes in steps and SSB consumption per day, per week by study arm. RESULTS: During run-in, mothers averaged 8317 and youth 7508 steps per day. Compared with self-monitoring alone, gamification did not increase daily steps in mothers or youth beyond baseline levels. On average, SSB intake decreased in mothers by approximately 0.5 servings per day; occurred in both arms and persisted throughout the intervention. CONCLUSION: Gamification did not promote physical activity levels in mother-youth dyads with obesity. SSB intake declined in mothers with obesity in both study arms.

Clinical application of tumour-in-normal contamination assessment from whole genome sequencing.

The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of [Formula: see text] patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care.

Ethical considerations in using sensors to remotely assess pediatric health behaviors.

Sensors, including accelerometer-based and electronic adherence monitoring devices, have transformed health data collection. Sensors allow for unobtrusive, real-time sampling of health behaviors that relate to psychological health, including sleep, physical activity, and medication-taking. These technical strengths have captured scholarly attention, with far less discussion about the level of human touch involved in implementing sensors. Researchers face several subjective decision points when collecting health data via sensors, with these decisions posing ethical concerns for users and the public at large. Using examples from pediatric sleep, physical activity, and medication adherence research, we pose critical ethical questions, practical dilemmas, and guidance for implementing health-based sensors. We focus on youth given that they are often deemed the ideal population for digital health approaches but have unique technology-related vulnerabilities and preferences. Ethical considerations are organized according to Belmont principles of respect for persons (e.g., when sensor-based data are valued above the subjective lived experiences of youth and their families), beneficence (e.g., with sensor data management and sharing), and justice (e.g., with sensor access and acceptability among minoritized pediatric populations). Recommendations include the need to increase transparency about the extent of subjective decision making with sensor data management. Without greater attention to the human factors involved in sensor research, ethical risks could outweigh the scientific promise of sensors, thereby negating their potential role in improving child health and care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme.

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). Homologous recombination deficiency was identified in 40% of high-grade serous ovarian cancer cases with 30% linked to pathogenic germline variants, highlighting the value of combined somatic and germline analysis. The linkage of WGS and longitudinal life course clinical data allowed the assessment of treatment outcomes for patients stratified according to pangenomic markers. Our findings demonstrate the utility of linking genomic and real-world clinical data to enable survival analysis to identify cancer genes that affect prognosis and advance our understanding of how cancer genomics impacts patient outcomes.

Enhancing patient safety: A national standard for cyber resiliency in healthcare.

With support from Public Safety Canada's Cyber Security Cooperation Program, HealthCareCAN and the Digital Governance Council developed a new standard to support cyber resiliency in Canada's healthcare system. With a clear framework and enhanced cybersecurity capabilities, healthcare organizations will be better protected from cybercrime, allowing them to respond more effectively to evolving threats and defend critical infrastructure. Health and information technology leaders can derive practical guidance and next steps from this three-year national project to enhance cyber resilience and improve safety within their organizations.

The missing link? LGMN connects hypoxia and immunosuppression in glioblastoma.

In this issue, Pang and colleagues1 identify the protease legumain as a potential immunotherapy target in glioblastoma that drives tumor-associated macrophages in response to hypoxia.

Rare variant associations with plasma protein levels in the UK Biobank.

Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers and discover drug targets1-4. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to the plasma proteome remains largely unknown. Here we identify associations between rare protein-coding variants and 2,923 plasma protein abundances measured in 49,736 UK Biobank individuals. Our variant-level exome-wide association study identified 5,433 rare genotype-protein associations, of which 81% were undetected in a previous genome-wide association study of the same cohort5. We then looked at aggregate signals using gene-level collapsing analysis, which revealed 1,962 gene-protein associations. Of the 691 gene-level signals from protein-truncating variants, 99.4% were associated with decreased protein levels. STAB1 and STAB2, encoding scavenger receptors involved in plasma protein clearance, emerged as pleiotropic loci, with 77 and 41 protein associations, respectively. We demonstrate the utility of our publicly accessible resource through several applications. These include detailing an allelic series in NLRC4, identifying potential biomarkers for a fatty liver disease-associated variant in HSD17B13 and bolstering phenome-wide association studies by integrating protein quantitative trait loci with protein-truncating variants in collapsing analyses. Finally, we uncover distinct proteomic consequences of clonal haematopoiesis (CH), including an association between TET2-CH and increased FLT3 levels. Our results highlight a considerable role for rare variation in plasma protein abundance and the value of proteogenomics in therapeutic discovery.

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort.

BACKGROUND: Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile. OBJECTIVES: This study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS). METHODS: This is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5-19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score. RESULTS: We obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and-2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian -0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black -0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score. CONCLUSIONS: These reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.

Transplant Center Attitudes Toward Early Liver Transplant for Alcohol-associated Liver Disease.

Background: Many centers have removed 6-mo pretransplant alcohol abstinence requirements to provide early liver transplant (ELT) for individuals with severe alcohol-associated liver disease (ALD), but the practice remains controversial. Using data collected from a nationally distributed survey, this study examines the practices and attitudes of transplant centers in the United States regarding ELT. Methods: A 20-item survey designed to assess center practices and provider attitudes was distributed to 225 medical and surgical directors from 143 liver transplant centers via email. Results: Surveys were completed by 28.9% (n = 65) of directors and 39% (n = 56) of transplant centers. All responding centers reported evaluating patients for ELT. Circumstances for considering ELT included <6 mo of survival without a transplant (96.4%) and inability to participate in alcohol addiction therapy pretransplant (75%). Most (66%) directors indicated their center had established criteria for listing candidates with severe ALD for ELT. Regarding important factors for ELT candidate listing, 57.1% indicated patient survival, 37.5% indicated graft survival, and 55.4% indicated having a low risk of relapse. Only 12.7% of directors affirmed the statement, "Six months of pretransplant abstinence decreases the risk of relapse." Conclusions: More centers are providing ELT for severe ALD. Inability to participate in alcohol addiction therapy and <6 mo of survival are commonly reported circumstances for considering ELT. Continued investigation of posttransplant outcomes in patients receiving ELT is essential to establishing a national consensus for distributing this valuable resource.

Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice.

Inflammatory bowel disease (IBD) is a multifactorial disease with increasing incidence in the U.S. suggesting that environmental factors, including diet, are involved. It has been suggested that excessive consumption of linoleic acid (LA, C18:2 omega-6), which must be obtained from the diet, may promote the development of IBD in humans. To demonstrate a causal link between LA and IBD, we show that a high fat diet (HFD) based on soybean oil (SO), which is comprised of ~55% LA, increases susceptibility to colitis in several models, including IBD-susceptible IL10 knockout mice. This effect was not observed with low-LA HFDs derived from genetically modified soybean oil or olive oil. The conventional SO HFD causes classical IBD symptoms including immune dysfunction, increased intestinal epithelial barrier permeability, and disruption of the balance of isoforms from the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). The SO HFD causes gut dysbiosis, including increased abundance of an endogenous adherent invasive Escherichia coli (AIEC), which can use LA as a carbon source. Metabolomic analysis shows that in the mouse gut, even in the absence of bacteria, the presence of soybean oil increases levels of LA, oxylipins and prostaglandins. Many compounds in the endocannabinoid system, which are protective against IBD, are decreased by SO both in vivo and in vitro. These results indicate that a high LA diet increases susceptibility to colitis via microbial and host-initiated pathways involving alterations in the balance of bioactive metabolites of omega-6 and omega-3 polyunsaturated fatty acids, as well as HNF4α isoforms.

The neighborhood environment and sleep health in adolescents.

OBJECTIVE: Neighborhood-level factors, including education, health and environment, and socioeconomic exposures, are important contextual determinants of child health. We explored whether these factors, measured via the Childhood Opportunity Index 2.0, were associated with sleep health in adolescents. METHODS: Actigraphy was used to assess sleep duration, timing, and efficiency among 110 adolescents in eighth (13.9 (0.4)) and ninth (14.9 (0.4)) grade. Home addresses were geocoded and linked to Childhood Opportunity Index 2.0 scores (including 3 subtype scores and the 29 individual factor Z-scores). Mixed-effects linear regression was used to determine associations between the Childhood Opportunity Index 2.0 scores and the sleep outcomes, adjusting for sex, race, parent education, household income, school grade and weeknight status. Interactions were also tested by school grade, weeknight status, sex, and race. RESULTS: No associations were observed between overall or subtype scores with sleep outcomes in adolescents. However, we detected associations between select individual Childhood Opportunity Index 2.0 Z-scores, spanning health & environment and education domains, and sleep outcomes. For example, greater fine particulate matter was associated with later timing of sleep onset and offset; ozone concentration was associated with earlier sleep onset and offset; greater exposure to extreme temperature was associated with later sleep onset and offset and increased odds of optimal sleep efficiency. CONCLUSIONS: Specific neighborhood factors indexed by the Childhood Opportunity Index 2.0 were associated with sleep health among adolescents. In particular, neighborhood air quality measures were associated with sleep timing and efficiency, warranting further investigation.

Associations of bedroom PM2.5, CO2, temperature, humidity, and noise with sleep: An observational actigraphy study.

OBJECTIVE: Climate change and urbanization increasingly cause extreme conditions hazardous to health. The bedroom environment plays a key role for high-quality sleep. Studies objectively assessing multiple descriptors of the bedroom environment as well as sleep are scarce. METHODS: Particulate matter with a particle size <2.5 µm (PM2.5), temperature, humidity, carbon dioxide (CO2), barometric pressure, and noise levels were continuously measured for 14 consecutive days in the bedroom of 62 participants (62.9% female, mean ± SD age: 47.7 ± 13.2 years) who wore a wrist actigraph and completed daily morning surveys and sleep logs. RESULTS: In a hierarchical mixed effect model that included all environmental variables and adjusted for elapsed sleep time and multiple demographic and behavioral variables, sleep efficiency calculated for consecutive 1-hour periods decreased in a dose-dependent manner with increasing levels of PM2.5, temperature, CO2, and noise. Sleep efficiency in the highest exposure quintiles was 3.2% (PM2.5, p < .05), 3.4% (temperature, p < .05), 4.0% (CO2, p < .01), and 4.7% (noise, p < .0001) lower compared to the lowest exposure quintiles (all p-values adjusted for multiple testing). Barometric pressure and humidity were not associated with sleep efficiency. Bedroom humidity was associated with subjectively assessed sleepiness and poor sleep quality (both p < .05), but otherwise environmental variables were not statistically significantly associated with actigraphically assessed total sleep time and wake after sleep onset or with subjectively assessed sleep onset latency, sleep quality, and sleepiness. Assessments of bedroom comfort suggest subjective habituation irrespective of exposure levels. CONCLUSIONS: These findings add to a growing body of evidence highlighting the importance of the bedroom environment-beyond the mattress-for high-quality sleep.

Feasibility and acceptability of mobile methods to assess home and neighborhood environments related to adolescent sleep.

OBJECTIVE: A growing evidence base suggests home and neighborhood environmental exposures may influence adolescent sleep, but few studies have assessed these relationships using methods that account for time-varying, location-specific exposures, or multiple neighborhood contexts. This study aimed to assess the feasibility and acceptability of using smartphone global positioning system (GPS) tracking and ecological momentary assessment (EMA) to assess time-varying home and neighborhood environmental exposures hypothesized to be associated with adolescent sleep. METHODS: Adolescents aged 15-17 years in Philadelphia completed 7 days of continuous smartphone GPS tracking, which was used to identify daily levels of exposure to geocoded neighborhood factors (eg, crime, green space). Four daily EMA surveys assessed home sleep environment (eg, noise, light), stress, health behaviors, and neighborhood perceptions. Feasibility and acceptability of GPS tracking and EMA were assessed, and distributions of daily environmental exposures were examined. RESULTS: Among 25 teens (mean age 16, 56% male), there was a high level of GPS location data captured (median daily follow-up: 24 hours). Seventy-eight percent of EMA surveys were completed overall. Most participants (96%) reported no privacy concerns related to GPS tracking and minimal burden from EMA surveys. Exposures differed between participants' home neighborhoods and locations visited outside the home neighborhood (eg, higher crime away from home). Sleep environment disruptions were present on 29% of nights (most common: uncomfortable temperature) and were reported by 52% of adolescents. CONCLUSIONS: Results demonstrate the feasibility and acceptability of mobile methods for assessing time-varying home and neighborhood exposures relevant to adolescent sleep for up to 1 week.

The impact of fear of hypoglycaemia on sleep in adolescents with type 1 diabetes.

AIMS: Fear of hypoglycaemia (FOH) can contribute to impaired sleep for adults with type 1 diabetes (T1D) and parents of children with T1D, although it is unknown how FOH may affect sleep for adolescents with T1D. This study examines the relationship between adolescent FOH and sleep and assessed the influences of continuous glucose monitor (CGM) and insulin pump use. METHODS: Adolescents ages 14-18 years with T1D completed questionnaires evaluating FOH (Child Hypoglycemia Fear Survey) and sleep (Pittsburgh Sleep Quality Index, PSQI). Analyses included linear and logistic regression, t-tests and Fisher's exact tests. RESULTS: Participants included 95 adolescents (52 female) with a median (IQR) age of 16.5 (15.3-17.7) years and a T1D duration of 5.7 (2.5-9.6) years. Analyses showed increased FOH-Worry subscale scores were associated with reduced sleep duration (ß = -0.03, p = 0.042, adjusting for BMI z-score, race and ethnicity) and increased sleep disturbances (OR = 1.1, p = 0.038, adjusting for race and ethnicity). Frequent CGM users had longer sleep duration (average 7.5 h) compared with infrequent or non-CGM users (average = 6.8 h; p = 0.029), and pump users had overall improved sleep health as determined by PSQI score (p = 0.019). Technology use did not have significant interactions in the relationships between FOH and sleep duration or sleep disturbances. CONCLUSIONS: Worrying about hypoglycaemia was associated with impaired sleep for adolescents with T1D. Diabetes technology users have some sleep improvements, but CGM and pump use do little to alter the relationship between FOH and sleep outcomes.

Promoting Sleep Duration in the Pediatric Setting Using a Mobile Health Platform: A Randomized Optimization Trial.

Objective: Determine the optimal combination of digital health intervention component settings that increase average sleep duration by ≥30 minutes per weeknight. Methods: Optimization trial using a 25 factorial design. The trial included 2 week run-in, 7 week intervention, and 2 week follow-up periods. Typically developing children aged 9-12y, with weeknight sleep duration <8.5 hours were enrolled (N=97). All received sleep monitoring and performance feedback. The five candidate intervention components (with their settings to which participants were randomized) were: 1) sleep goal (guideline-based or personalized); 2) screen time reduction messaging (inactive or active); 3) daily routine establishing messaging (inactive or active); 4) child-directed loss-framed financial incentive (inactive or active); and 5) caregiver-directed loss-framed financial incentive (inactive or active). The primary outcome was weeknight sleep duration (hours per night). The optimization criterion was: ≥30 minutes average increase in sleep duration on weeknights. Results: Average baseline sleep duration was 7.7 hours per night. The highest ranked combination included the core intervention plus the following intervention components: sleep goal (either setting was effective), caregiver-directed loss-framed incentive, messaging to reduce screen time, and messaging to establish daily routines. This combination increased weeknight sleep duration by an average of 39.6 (95% CI: 36.0, 43.1) minutes during the intervention period and by 33.2 (95% CI: 28.9, 37.4) minutes during the follow-up period. Conclusions: Optimal combinations of digital health intervention component settings were identified that effectively increased weeknight sleep duration. This could be a valuable remote patient monitoring approach to treat insufficient sleep in the pediatric setting.