It is well established that electrons can escape from atoms through tunneling under the influence of strong laser fields, but the timing of the process has been controversial and far too rapid to ...probe in detail. We used attosecond angular streaking to place an upper limit of 34 attoseconds and an intensity-averaged upper limit of 12 attoseconds on the tunneling delay time in strong field ionization of a helium atom. The ionization field derives from 5.5-femtosecond-long near-infrared laser pulses with peak intensities ranging from 2.3 x 10¹⁴ to 3.5 x 10¹⁴ watts per square centimeter (corresponding to a Keldysh parameter variation from 1.45 to 1.17, associated with the onset of efficient tunneling). The technique relies on establishing an absolute reference point in the laboratory frame by elliptical polarization of the laser pulse, from which field-induced momentum shifts of the emergent electron can be assigned to a temporal delay on the basis of the known oscillation of the field vector.
Aims
To investigate the best glucose monitoring strategy for maintaining euglycaemia by comparing self‐monitoring of blood glucose with continuous glucose monitoring, with or without an alarm ...function.
Methods
A 100‐day, randomized controlled study was conducted at four European centres, enrolling 160 patients with Type 1 or Type 2 diabetes, on multiple daily insulin injections or continuous subcutaneous insulin infusion. Participants were randomized to continuous glucose monitoring without alarms (n = 48), continuous glucose monitoring with alarms (n = 49) or self‐monitoring of blood glucose (n = 48).
Results
Time spent outside the glucose target during days 80–100 was 9.9 h/day for the continuous glucose monitoring without alarms group, 9.7 h/day for the continuous glucose monitoring with alarms group and 10.6 h/day for the self‐monitoring of blood glucose group (P = 0.18 and 0.08 compared with continuous glucose monitoring without and with alarms, respectively).The continuous glucose monitoring with alarms group spent less time in hypoglycaemia compared with the self‐monitoring of blood glucose group (1.0 h/day and 1.6 h/day, respectively; 95% CI −1.2 to −0.1; P = 0.030). Among those treated with continuous subcutaneous insulin infusion, time spent outside the glucose target was significantly different when comparing continuous glucose monitoring without alarms and self‐monitoring of blood glucose (−1.9 h/day; 95% CI −3.8 to 0.0; P = 0.0461) and when comparing continuous glucose monitoring with alarms and self‐monitoring of blood glucose (−2.4 h/day; 95% CI −4.1 to −0.5; P = 0.0134). There was no difference in HbA1c reduction from baseline in the three groups; however, the proportion of participants with a reduction of ≥ 6 mmol/mol (≥ 0.5%) was higher in the continuous glucose monitoring without alarms (27%) and continuous glucose monitoring with alarms groups (25%) than in the self‐monitoring of blood glucose group (10.6%).
Conclusions
This study shows that the use of continuous glucose monitoring reduces time spent outside glucose targets compared with self‐monitoring of blood glucose, especially among users of insulin pumps.
What's new?
In this study, time spent outside glucose target was not significantly different between continuous glucose monitoring with and without alarm groups. The proportion of participants with an HbA1c concentration reduction ≥ 6 mmol/mol (≥ 0.5%) was similar in the two continuous glucose monitoring groups.
This indicates that, for certain individuals, continuous glucose monitoring without alarms may be as beneficial and safe as continuous glucose monitoring with alarms compared with conventional self‐monitoring of blood glucose.
High frequency of alarms, especially false alarms, may lead to alarm fatigue, making users less likely to respond appropriately.
The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the ...circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters.
Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR.
The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1).
Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.
Aims/hypothesis
Glucagon reduces body weight by modifying food intake, glucose/lipid metabolism and energy expenditure. All these physiological processes are also controlled by fibroblast growth ...factor 21 (FGF-21), a circulating hepatokine that improves the metabolic profile in obesity and type 2 diabetes. Animal experiments have suggested a possible interaction between glucagon and FGF-21 however, the metabolic consequences of this crosstalk are not understood.
Methods
The effects of exogenous glucagon on plasma FGF-21 levels and lipolysis were evaluated in healthy volunteers and humans with type 1 diabetes, as well as in rodents with streptozotocin (STZ)-induced insulinopenic diabetes. In vitro, the role of glucagon on FGF-21 secretion and lipolysis was studied using isolated primary rat hepatocytes and adipocytes.
Fgf-21
expression in differentiated rat pre-adipocytes was suppressed by small interfering RNA and released FGF-21 was immunoneutralised by polyclonal antibodies.
Results
Glucagon induced lipolysis in healthy human volunteers, patients with type 1 diabetes, mice and rats with STZ-induced insulinopenic diabetes, and in adipocytes isolated from diabetic and non-diabetic animals. In addition, glucagon increased circulating FGF-21 in healthy humans and rodents, as well as in patients with type 1 diabetes, and insulinopenic rodents. Glucagon stimulated FGF-21 secretion from isolated primary hepatocytes and adipocytes derived from animals with insulinopenic diabetes. Furthermore, FGF-21 stimulated lipolysis in primary adipocytes isolated from non-diabetic and diabetic rats. Reduction of
Fgf-21
expression (by approximately 66%) or immunoneutralisation of released FGF-21 markedly attenuated glucagon-stimulated lipolysis in adipocytes.
Conclusions/interpretation
These results indicate that glucagon increases circulating FGF-21 independently of endogenous insulin levels. FGF-21 participates in glucagon-induced stimulation of lipolysis.
Single-cell CRISPR screens enable the exploration of mammalian gene function and genetic regulatory networks. However, use of this technology has been limited by reliance on indirect indexing of ...single-guide RNAs (sgRNAs). Here we present direct-capture Perturb-seq, a versatile screening approach in which expressed sgRNAs are sequenced alongside single-cell transcriptomes. Direct-capture Perturb-seq enables detection of multiple distinct sgRNA sequences from individual cells and thus allows pooled single-cell CRISPR screens to be easily paired with combinatorial perturbation libraries that contain dual-guide expression vectors. We demonstrate the utility of this approach for high-throughput investigations of genetic interactions and, leveraging this ability, dissect epistatic interactions between cholesterol biogenesis and DNA repair. Using direct capture Perturb-seq, we also show that targeting individual genes with multiple sgRNAs per cell improves efficacy of CRISPR interference and activation, facilitating the use of compact, highly active CRISPR libraries for single-cell screens. Last, we show that hybridization-based target enrichment permits sensitive, specific sequencing of informative transcripts from single-cell RNA-seq experiments.
Empirical studies have validated that basic needs satisfaction supported by video game play predicts motivation and engagement outcomes. However, few studies specifically manipulated game features ...for each of the three basic needs specified in the self-determination theory (SDT) to examine how the game features impact players' need satisfaction and game experience. The current study employed an in-house developed exergame and manipulated the game features in a 2 (autonomy-supportive game features: on vs. off) × 2 (competence-supportive game features: on vs. off) experiment to predict need satisfaction, game enjoyment, motivation for future play, effort for gameplay, self-efficacy for exercise using the game, likelihood of game recommendation, and game rating. The manipulated game features led to the corresponding need satisfaction. Manipulated autonomy-supportive and competence-supportive game features had main effects on most motivation and engagement outcomes. Need satisfaction of autonomy and need satisfaction of competence were both found to be mediators for the relationships between the game features and the motivation and engagement outcomes. The findings add evidence to support the underlying mechanism postulated by SDT for media enjoyment and motivation as well as the emerging entertainment research conceptualizing enjoyment as need satisfaction. The findings also have practical implications for intervention effort that intends to capitalize the motivational pull of video games.
While socio-economic status has been shown to be an important determinant of health and physical activity in adults, results for children and adolescents are less consistent. The purpose of this ...study, therefore, is to examine whether physical activity and sedentary behavior differs in children by socio-economic status (SES) independent of body mass index.
Data were from two cohorts including 271 children (117 males; 154 females) in study 1 and 131 children in study 2 (63 males; 68 females). The average age was 9.6 and 8.8 years respectively. Height and body mass were assessed according to standard procedures and body mass index (BMI, kg/m2) was calculated. Parent-reported household income was used to determine SES. Habitual, free-living physical activity (PA) was assessed by a pedometer (steps/day) in study 1 and accelerometer (time spent in moderate-to-vigorous PA) in study 2. Self-reported time spent watching TV and on the computer was used as measure of sedentary behavior. Differences in PA and sedentary behavior by SES were initially tested using ANOVA. Further analyses used ANCOVA controlling for BMI, as well as leg length in the pedometer cohort.
In study 1, mean daily steps differed significantly among SES groups with lower SES groups approximating 10,500 steps/day compared to about 12,000 steps/day in the higher SES groups. These differences remained significant (p < 0.05) when controlling for leg length. Lower SES children, however, had higher body mass and BMI compared to higher SES groups (p < 0.05) and PA no longer remained significant when further controlling for BMI. In study 2 results depended on the methodology used to determine time spent in moderate-to-vigorous physical activity (MVPA). Only one equation resulted in significant group differences (p = 0.015), and these differences remained after controlling for BMI. Significant differences between SES groups were shown for sedentary behavior in both cohorts (P < 0.05) with higher SES groups spending less time watching TV than low SES groups.
Children from a low SES show a trend of lower PA levels and spend more time in sedentary behavior than high SES children; however, differences in PA were influenced by BMI. The higher BMI in these children might be another factor contributing to increased health risks among low SES children compared to children from with a higher SES.
Studies have reported sex and race/ethnicity disparities in sedentary time (ST), but none have evaluated ST by well-defined periods of the weekday (before school, during school, afterschool, and ...evening) and weekend day (morning, afternoon, and evening). Comparing sex and race/ethnicity disparities in ST at different periods of a weekday and weekend day can deepen our understanding of disparities and inform intervention efforts. This study tests sex and race/ethnicity disparities in ST by period of day in a representative sample of US youth.
Youth (N = 2,972) from the 2003-2006 NHANES waves reported demographic variables and wore an accelerometer for 7 consecutive days to assess ST. Linear regressions were conducted to test relationships between sex and race/ethnicity and ST (min/hour) during each period of a weekday and weekend day. ST differences by sex and race/ethnicity were calculated to identify the periods of the day presenting the largest opportunity to reduce disparities.
Females were more sedentary than males during school (p < 0∙0001), afterschool (p < 0∙0001), and weekday evenings (p < 0∙0001) after controlling for covariates. After controlling for covariates, race/ethnicity only was a significant predictor of ST during weekend mornings (p < 0∙0001). During school and afterschool emerged as the periods with the largest opportunities to reduce sex disparities in ST. Weekend mornings were identified as the largest opportunity to reduce race/ethnic disparities in ST.
Sex disparities in ST appear to be driven mostly by the during school period of the day, while race/ethnic disparities in ST seem to be driven by the weekend morning period. Future intervention work should consider these periods when aiming to reduce ST disparities in youth.
We present an ellipticity-resolved study of momentum distributions arising from strong-field ionization of helium. The influence of the ion potential on the departing electron is considered within a ...semiclassical model consisting of an initial tunneling step and subsequent classical propagation. We find that the momentum distribution can be explained by including the longitudinal momentum spread of the electron at the exit from the tunnel. Our combined experimental and theoretical study provides an estimate of this momentum spread.
Objective: Obesity rates in young children are increasing, and decreased physical activity is likely to be a major contributor to this trend. Studies of physical activity in young children are ...limited by the lack of valid and acceptable measures. The purpose of this study was to calibrate and validate the ActiGraph accelerometer for use with 3‐ to 5‐year‐old children.
Research Methods and Procedures: Thirty preschool children wore an ActiGraph accelerometer (ActiGraph, Fort Walton Beach, FL) and a Cosmed portable metabolic system (Cosmed, Rome, Italy) during a period of rest and while performing three structured physical activities in a laboratory setting. Expired respiratory gases were collected, and oxygen consumption was measured on a breath‐by‐breath basis. Accelerometer data were collected at 15‐second intervals. For cross‐validation, the same children wore the same instruments while participating in unstructured indoor and outdoor activities for 20 minutes each at their preschool.
Results: In calibrating the accelerometer, the correlation between V̇o2 (ml/kg per min) and counts was r = 0.82 across all activities. The only significant variable in the prediction equation was accelerometer counts (R2 = 0.90, standard error of the estimate = 4.70). In the cross‐validation, the intraclass correlation coefficient between measured and predicted V̇o2 was R = 0.57 and the Spearman correlation coefficient was R = 0.66 (p < 0.001). Cut‐off points for moderate‐ and vigorous‐intensity physical activity were identified at 420 counts/15 s (V̇o2 = 20 mL/kg per min) and 842 counts/15 s (V̇o2 = 30 mL/kg per min), respectively. When these cutpoints were applied to the cross‐validation data, percentage agreement, kappa, and modified kappa for moderate activity were 0.69, 0.36, and 0.38, respectively. For vigorous activity, the same measures were 0.81, 0.13, and 0.62.
Discussion: Accelerometer counts were highly correlated with V̇o2 in young children. Accelerometers can be appropriately used as a measure of physical activity in this population.
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