The "Goldilocks Day" for Children's Skeletal Health: Compositional Data Analysis of 24-Hour Activity Behaviors

Optimization of children's activity behaviors for skeletal health is a key public health priority, yet it is unknown how many hours of moderate to vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior, or sleep constitute the best day-the "Goldilocks Day"-for children's bone structure and function. To describe the best day for children's skeletal health, we used data from the cross-sectional Child Health CheckPoint. Included participants (n= 804, aged 10.7 to 12.9 years, 50% male) underwent tibial peripheral quantitative CT to assesses cross-sectional area, trabecular and cortical density, periosteal and endosteal circumference, polar moment of inertia, and polar stress-strain index. Average daily time-use composition (MVPA, LPA, sedentary time, and sleep) was assessed through 8-day, 24-hour accelerometry. Skeletal outcomes were regressed against time-use compositions expressed as isometric log-ratios (with quadratic terms where indicated), adjusted for sex, age, pubertal status, and socioeconomic position. The models were used to estimate optimal time-use compositions (associated with best 5% of each skeletal outcome), which were plotted in three-dimensional quaternary figures. The center of the overlapping area was considered the Goldilocks Day for skeletal health. Children's time-use composition was associated with all skeletal measures (allp <= 0.001) except cross-sectional area (p= 0.72). Days with more sleep and MVPA, less sedentary time, and moderate LPA were beneficially associated with skeletal measures, except cortical density, which was adversely associated. The Goldilocks daily time-use composition for overall skeletal health was center (range): 10.9 (10.5 to 11.5) hours sleep; 8.2 (7.8 to 8.8) hours sedentary time; 3.4 (2.8 to 4.2) hours LPA, and 1.5 (1.3 to 1.5) hours MVPA. Estimated optimal sleep duration is consistent with current international guidelines (9 to 11 hours), while estimated optimal MVPA exceeds recommendations of at least 60 min/d. This first study to describe optimal durations of daily activities for children's skeletal health provides evidence to underpin guidelines.

Mechanism of sphingolipid homeostasis revealed by structural analysis of \u3ci\u3eArabidopsis\u3c/i\u3e SPT-ORM1 complex

The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeostatic regulation of SPT is not well understood.We determined the cryo–electron microscopy structure of Arabidopsis SPT-ORM1 complex, composed of LCB1, LCB2a, SPTssa, and ORM1, in an inhibited state. A ceramide molecule is sandwiched between ORM1 and LCB2a in the cytosolic membrane leaflet. Ceramide binding is critical for the ORM1-dependent SPT repression, and dihydroceramides and phytoceramides differentially affect this repression. A hybrid β sheet, formed by the amino termini of ORM1 and LCB2a and induced by ceramide binding, stabilizes the amino terminus of ORM1 in an inhibitory conformation. Our findings provide mechanistic insights into sphingolipid homeostatic regulation via the binding of ceramide to the SPT-ORM/ORMDL complex that may have implications for plant-specific processes such as the hypersensitive response for microbial pathogen resistance

Experimental quantum adversarial learning with programmable superconducting qubits

Quantum computing promises to enhance machine learning and artificial intelligence. Different quantum algorithms have been proposed to improve a wide spectrum of machine learning tasks. Yet, recent theoretical works show that, similar to traditional classifiers based on deep classical neural networks, quantum classifiers would suffer from the vulnerability problem: adding tiny carefully-crafted perturbations to the legitimate original data samples would facilitate incorrect predictions at a notably high confidence level. This will pose serious problems for future quantum machine learning applications in safety and security-critical scenarios. Here, we report the first experimental demonstration of quantum adversarial learning with programmable superconducting qubits. We train quantum classifiers, which are built upon variational quantum circuits consisting of ten transmon qubits featuring average lifetimes of 150 $\mu$s, and average fidelities of simultaneous single- and two-qubit gates above 99.94% and 99.4% respectively, with both real-life images (e.g., medical magnetic resonance imaging scans) and quantum data. We demonstrate that these well-trained classifiers (with testing accuracy up to 99%) can be practically deceived by small adversarial perturbations, whereas an adversarial training process would significantly enhance their robustness to such perturbations. Our results reveal experimentally a crucial vulnerability aspect of quantum learning systems under adversarial scenarios and demonstrate an effective defense strategy against adversarial attacks, which provide a valuable guide for quantum artificial intelligence applications with both near-term and future quantum devices.Comment: 26 pages, 17 figures, 8 algorithm

Impact of within-visit systolic blood pressure change patterns on blood pressure classification : the Cardiovascular Risk in Young Finns Study

AIMS: Most international guidelines recommend that repeat blood pressure (BP) readings are required for BP classification. Two international guidelines diverge from this by recommending that no further BP measurements are required if the first clinic BP is below a hypertension threshold. The extent to which within-visit BP variability patterns change over time, and whether this could impact BP classification is unknown. We sought to examine this. METHODS AND RESULTS: Data were from the Cardiovascular Risk in Young Finns Study, a prospective cohort study. Up to 2799 participants were followed from childhood (9-15 years) to adulthood (18-49 years) over up to six visits. Patterns of within-visit systolic BP (SBP) variability were defined as no-change, decrease, increase between consecutive readings (with 5 mmHg change thresholds). Classification of SBP (normal, high-normal, hypertension) using the first reading was compared with repeat readings. On average, SBP decreased with subsequent measures, but with major individual variability (no-change: 56.9-62.7%; decrease: 24.1-31.6%; increase: 11.5-16.8%). Patterns of SBP variability were broadly similar from childhood to adulthood, with the highest prevalence of an increase among participants categorized with normal SBP (12.6-20.3%). The highest prevalence of SBP reclassification occurred among participants with hypertension (28.9-45.3% reclassified as normal or high-normal). The prevalence of reclassification increased with the magnitude of change between readings. CONCLUSION: There is a major individual variation of within-visit SBP change in childhood and adulthood and can influence BP classification. This highlights the importance of consistency among guidelines recommending that repeat BP measurements are needed for BP classification.publishedVersionPeer reviewe

Observation of many-body Fock space dynamics in two dimensions

Quantum many-body simulation provides a straightforward way to understand fundamental physics and connect with quantum information applications. However, suffering from exponentially growing Hilbert space size, characterization in terms of few-body probes in real space is often insufficient to tackle challenging problems such as quantum critical behavior and many-body localization (MBL) in higher dimensions. Here, we experimentally employ a new paradigm on a superconducting quantum processor, exploring such elusive questions from a Fock space view: mapping the many-body system onto an unconventional Anderson model on a complex Fock space network of many-body states. By observing the wave packet propagating in Fock space and the emergence of a statistical ergodic ensemble, we reveal a fresh picture for characterizing representative many-body dynamics: thermalization, localization, and scarring. In addition, we observe a quantum critical regime of anomalously enhanced wave packet width and deduce a critical point from the maximum wave packet fluctuations, which lend support for the two-dimensional MBL transition in finite-sized systems. Our work unveils a new perspective of exploring many-body physics in Fock space, demonstrating its practical applications on contentious MBL aspects such as criticality and dimensionality. Moreover, the entire protocol is universal and scalable, paving the way to finally solve a broader range of controversial many-body problems on future larger quantum devices.Comment: 8 pages, 4 figures + supplementary informatio

Within-visit SBP variability from childhood to adulthood and markers of cardiovascular end-organ damage in mid-life

Background: Within-visit SBP variability is associated with age and SBP, but its long-term clinical significance is unknown. We examined the association between child, adult, and life-time within-visit SBP variability with markers of end-organ damage using data from a 31-year longitudinal study.Methods: Within-visit SBP variability was calculated as the standard deviation of three sitting SBP readings among up to 3010 participants aged 6-18 years (childhood) who were re-measured up to seven times to mid-adulthood. Markers of cardiovascular end-organ damage in adulthood were carotid intima-media thickness, brachial flow-mediated dilatation, carotid distensibility, pulse wave velocity, left ventricular mass index, carotid plaque, and coronary artery calcification.Results: The mean (standard deviation) cumulative within-visit SBP variability was 2.7 (1.5) mmHg in childhood, 3.9 (1.9) mmHg in adulthood and 3.7 (1.5) mmHg across the observed life-time. Childhood within-visit SBP variability was not correlated with its subsequent values measured from 3 to 31 years later. With adjustment for age, sex, cumulative SBP, BMI and serum lipids, neither child, adult, or life-time cumulative within-visit SBP variability associated with markers of cardiovascular end-organ damage. However, higher child, adult, and life-time cumulative SBP significantly associated with higher carotid intima-media thickness, higher pulse wave velocity, lower brachial flow-mediated dilatation, lower carotid distensibility in adulthood.Conclusion: Within-visit SBP variability from childhood to adulthood does not provide additional predictive utility over SBP over the same period of the life course.</p

Age-Specific Estimates and Comparisons of Youth Tri-Ponderal Mass Index and Body Mass Index in Predicting Adult Obesity-Related Outcomes

ObjectivesTo estimate and compare tri-ponderal mass index (TMI) and body mass index (BMI) at each age from childhood to young adulthood in the prediction of adulthood obesity-related outcomes.Study designParticipants of this observational study (n = 432) were from a 20-year infancy-onset randomized atherosclerosis prevention trial. BMI and TMI were calculated using weight and height measured annually from participants between ages 2 and 20 years. Outcomes were aortic intima-media thickness (at the age of 15, 17, or 19 years), impaired fasting glucose and elevated insulin levels, homeostasis model assessment of insulin resistance index, serum lipids, and hypertension at the age of 20 years. Poisson regressions, Pearson correlation, logistic regression, and area under the curve (AUC) were used to estimate and/or compare associations and predictive utilities between BMI and TMI with all outcomes.ResultsThe associations and predictive utilities of BMI and TMI with all outcomes were stronger at older ages. BMI had significantly stronger correlations than TMI with insulin (at age 16 years), systolic blood pressure (age 5-20 years), and triglycerides (age 18 years). BMI had significantly greater predictive utilities than TMI for insulin resistance (at age 14-16 years; difference in AUC = 0.018-0.024), elevated insulin levels (age 14-16 years; difference in AUC = 0.018 and 0.025), and hypertension (age 16 to 20 years; difference in AUC = 0.017-0.022) but they were similar for other outcomes.ConclusionsTMI is not superior to BMI at any ages from childhood to young adulthood in the prediction of obesity-related outcomes in young adulthood.</p

Childhood and Adulthood Passive Smoking and Nonalcoholic Fatty Liver in Midlife: A 31-year Cohort Study

INTRODUCTION: Identifying early life risk factors remains key to the prevention of nonalcoholic fatty liver (hereinafter "fatty liver") in adulthood. However, the longitudinal association of childhood passive smoking with adult fatty liver is not studied. We examined the association of childhood and adulthood passive smoking with fatty liver in midlife.METHODS: This was a 31-year prospective cohort study of 1,315 participants. Information on childhood passive smoking (parental smoking) was collected in 1980 (aged 3-18 years) and 1983 and adulthood passive smoking in 2001, 2007, and 2011. Fatty liver was determined by ultrasound in 2011 (aged 34-49 years).RESULTS. The prevalence of fatty liver was 16.3%. Both childhood and adulthood passive smoking were associated with higher risk of fatty liver, adjusting for potential confounders such as age, sex, childhood socioeconomic status, and adulthood physical activity and alcohol consumption (relative risk = 1.41, 95% confidence interval: 1.01-1.97 for childhood; 1.35, 1.01-1.82 for adulthood). Individuals with persistent exposure to passive smoking between childhood and adulthood had the highest risk (relative risk = 1.99, 95% confidence interval: 1.14-3.45) compared with those without passive smoking in either childhood or adulthood.DISCUSSION: Passive smoking in both child and adult lives are associated with increased risk of adult fatty liver, suggesting that the prevention of passive smoking should start as early as possible and maintain throughout lifetime

Impact of within-visit systolic blood pressure change patterns on blood pressure classification: the Cardiovascular Risk in Young Finns Study

Aims Most international guidelines recommend that repeat blood pressure (BP) readings are required for BP classification. Two international guidelines diverge from this by recommending that no further BP measurements are required if the first clinic BP is below a hypertension threshold. The extent to which within-visit BP variability patterns change over time, and whether this could impact BP classification is unknown. We sought to examine this.Methods and results Data were from the Cardiovascular Risk in Young Finns Study, a prospective cohort study. Up to 2799 participants were followed from childhood (9-15 years) to adulthood (18-49 years) over up to six visits. Patterns of within-visit systolic BP (SBP) variability were defined as no-change, decrease, increase between consecutive readings (with 5 mmHg change thresholds). Classification of SBP (normal, high-normal, hypertension) using the first reading was compared with repeat readings. On average, SBP decreased with subsequent measures, but with major individual variability (no-change: 56.9-62.7%; decrease: 24.1-31.6%; increase: 11.5-16.8%). Patterns of SBP variability were broadly similar from childhood to adulthood, with the highest prevalence of an increase among participants categorized with normal SBP (12.6-20.3%). The highest prevalence of SBP reclassification occurred among participants with hypertension (28.9-45.3% reclassified as normal or high-normal). The prevalence of reclassification increased with the magnitude of change between readings.Conclusion There is a major individual variation of within-visit SBP change in childhood and adulthood and can influence BP classification. This highlights the importance of consistency among guidelines recommending that repeat BP measurements are needed for BP classification.</p

Childhood and long-term dietary calcium intake and adult cardiovascular risk in a population with high calcium intake

Background & aimsThe influence of dietary calcium intake in childhood on adult cardiovascular health is unknown, particularly in those with long-term high intake. To examine both linear and non-linear associations of childhood and long-term (between childhood and adulthood) dietary calcium intake with adult cardiovascular risk outcomes.MethodsA population-based prospective cohort study in Finland (n = 1029, aged 3–18 years at baseline). Dietary calcium intake was assessed in childhood (1980, baseline) and adulthood (mean of available data from 2001, 2007 and 2011). Long-term dietary calcium intake was calculated as the mean between childhood and adulthood. Outcomes were measured in 2001, 2007, and/or 2011, and the latest available data were used for analyses, including high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity (PWV), carotid artery compliance (CAC), Young's elastic modulus (YEM), and stiffness index (SI).ResultsThere were no significant non-linear or linear associations between childhood or long-term dietary calcium intake with any adult cardiovascular outcomes, after adjustment for age, sex, and childhood and adulthood confounders (e.g., body mass index, systolic blood pressure, smoking, physical activity, fruit and vegetable consumption).ConclusionsChildhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood.</p