AMPK regulates phagophore-to-autophagosome maturation.

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation. Autophagy can be activated by nutrient stress, for example, by a reduction in the cellular levels of amino acids. In contrast, how autophagy is regulated by low cellular ATP levels via the AMP-activated protein kinase (AMPK), an important therapeutic target, is less clear. Using live-cell imaging and an automated image analysis pipeline, we systematically dissect how nutrient starvation regulates autophagosome biogenesis. We demonstrate that glucose starvation downregulates autophagosome maturation by AMPK-mediated inhibition of phagophore tethering to donor membrane. Our results clarify AMPKs regulatory role in autophagy and highlight its potential as a therapeutic target to reduce autophagy.

The effect of task load, information reliability and interdependency on anticipation performance.

In sport, coaches often explicitly provide athletes with stable contextual information related to opponent action preferences to enhance anticipation performance. This information can be dependent on, or independent of, dynamic contextual information that only emerges during the sequence of play (e.g. opponent positioning). The interdependency between contextual information sources, and the associated cognitive demands of integrating information sources during anticipation, has not yet been systematically examined. We used a temporal occlusion paradigm to alter the reliability of contextual and kinematic information during the early, mid- and final phases of a two-versus-two soccer anticipation task. A dual-task paradigm was incorporated to investigate the impact of task load on skilled soccer players' ability to integrate information and update their judgements in each phase. Across conditions, participants received no contextual information (control) or stable contextual information (opponent preferences) that was dependent on, or independent of, dynamic contextual information (opponent positioning). As predicted, participants used reliable contextual and kinematic information to enhance anticipation. Further exploratory analysis suggested that increased task load detrimentally affected anticipation accuracy but only when both reliable contextual and kinematic information were available for integration in the final phase. This effect was observed irrespective of whether the stable contextual information was dependent on, or independent of, dynamic contextual information. Findings suggest that updating anticipatory judgements in the final phase of a sequence of play based on the integration of reliable contextual and kinematic information requires cognitive resources.

Early signs of myocardial systolic dysfunction in patients with type 2 diabetes are strongly associated with myocardial microvascular dysfunction independent of myocardial fibrosis: a prospective cohort study.

BACKGROUND: Patients with diabetes demonstrate early left ventricular systolic dysfunction. Notably reduced global longitudinal strain (GLS) is related to poor outcomes, the underlying pathophysiology is however still not clearly understood. We hypothesized that pathophysiologic changes with microvascular dysfunction and interstitial fibrosis contribute to reduced strain. METHODS: 211 patients with type 2 diabetes and 25 control subjects underwent comprehensive cardiovascular phenotyping by magnetic resonance imaging. Myocardial blood flow (MBF), perfusion reserve (MPR), extracellular volume (ECV), and 3D feature tracking GLS and global circumferential (GCS) and radial strain (GRS) were quantified. RESULTS: Patients (median age 57 [IQR 50, 67] years, 70% males) had a median diabetes duration of 12 [IQR 6, 18] years. Compared to control subjects GLS, GCS, and GRS were reduced in the total diabetes cohort, and GLS was also reduced in the sub-group of patients without diabetic complications compared to control subjects (controls - 13.9 ± 2.0%, total cohort - 11.6 ± 3.0%; subgroup - 12.3 ± 2.6%, all p < 0.05). Reduced GLS, but not GCS or GRS, was associated with classic diabetes complications of albuminuria (UACR ≥ 30 mg/g) [ß (95% CI) 1.09 (0.22-1.96)] and autonomic neuropathy [ß (95% CI) 1.43 (0.54-2.31)] but GLS was not associated with retinopathy or peripheral neuropathy. Independently of ECV, a 10% increase in MBF at stress and MPR was associated with higher GLS [multivariable regression adjusted for age, sex, hypertension, smoking, and ECV: MBF stress (ß (95% CI) - 0.2 (- 0.3 to - 0.08), MPR (ß (95% CI) - 0.5 (- 0.8 to - 0.3), p < 0.001 for both]. A 10% increase in ECV was associated with a decrease in GLS in univariable [ß (95% CI) 0.6 (0.2 to 1.1)] and multivariable regression, but this was abolished when adjusted for MPR [multivariable regression adjusted for age, sex, hypertension, smoking, and MPR (ß (95% CI) 0.1 (- 0.3 to 0.6)]. On the receiver operating characteristics curve, GLS showed a moderate ability to discriminate a significantly lowered stress MBF (AUC 0.72) and MPR (AUC 0.73). CONCLUSIONS: Myocardial microvascular dysfunction was independent of ECV, a biomarker of myocardial fibrosis, associated with GLS. Further, 3D GLS could be a potential screening tool for myocardial microvascular dysfunction. Future directions should focus on confirming these results in longitudinal and/or interventional studies.

The effect of rear bicycle light configurations on drivers' perception of cyclists' presence and proximity.

The optimal cycle light configuration for maximizing cyclists' conspicuity to drivers is not clear. Advances in sensor technology has led to the development of 'reactive' cycle lights that detect changes in the environment and consequently increase their flashing speed and brightness in risky situations - for example, when a rearward car is approaching - but no research has examined the effect of such lights on driver perception. The aim of the present study is to compare different cycle light configurations, including 'reactive' light technology, on drivers' ability to detect cyclists and estimate their proximity. We recruited 32 drivers to participate in two experiments, in which they viewed life-size real-world stimuli filmed from a driver's perspective in daytime and at dusk. The footage showed a cyclist on a bicycle with a rear light mounted on the seat post, in various configurations: static light, steady flashing, reactive flashing and no light. In Experiment 1, the drivers were required to detect the presence or absence of a cyclist on the road ahead as quickly as possible. In Experiment 2, they were required to estimate the distance of the cyclist from their vehicle, and to rate their confidence in their estimates. Experiment 1 revealed that drivers were quicker to detect the cyclist's presence in all rear cycle light conditions relative to the no light condition, but there were no differences in speed or accuracy across rear light conditions. Experiment 2 showed that drivers were more accurate in estimating the cyclist's proximity in the steady flashing and reactive flashing conditions, compared to static and no light conditions. Drivers were also more confident in their judgements in all rear light conditions compared to the no light condition. In conclusion, flashing rear cycle lights, regardless of reactive technology, enhanced drivers' perception of a cyclist ahead, notably in terms of their judgements of distance to that cyclist. Further investigation is needed to fully understand the impact of cycle light technology on driver perception, as well as the use of drivers' distance-to-cyclist estimates as an index of cyclists' cognitive conspicuity.

Myocardial Blood Flow Determination From Contrast-Free Magnetic Resonance Imaging Quantification of Coronary Sinus Flow.

BACKGROUND: Determination of myocardial blood flow (MBF) with MRI is usually performed with dynamic contrast enhanced imaging (MBFDCE ). MBF can also be determined from coronary sinus blood flow (MBFCS ), which has the advantage of being a noncontrast technique. However, comparative studies of MBFDCE and MBFCS in large cohorts are lacking. PURPOSE: To compare MBFCS and MBFDCE in a large cohort. STUDY TYPE: Prospective, sequence-comparison study. POPULATION: 147 patients with type 2 diabetes mellitus (age: 56+/-12 years; 106 male; diabetes duration: 12.9+/-8.1 years), and 25 age-matched controls. FIELD STRENGTH/SEQUENCES: 1.5 Tesla scanner. Saturation recovery sequence for MBFDCE vs. phase-contrast gradient-echo pulse sequence (free-breathing) for MBFCS . ASSESSMENT: MBFDCE and MBFCS were determined at rest and during coronary dilatation achieved by administration of adenosine at 140 µg/kg/min. Myocardial perfusion reserve (MPR) was calculated as the stress/rest ratio of MBF values. Coronary sinus flow was determined twice in the same imaging session for repeatability assessment. STATISTICAL TESTS: Agreement between MBFDCE and MBFCS was assessed with Bland and Altman's technique. Repeatability was determined from single-rater random intraclass and repeatability coefficients. RESULTS: Rest and stress flows, including both MBFDCE and MBFCS values, ranged from 33 to 146 mL/min/100 g and 92 to 501 mL/min/100 g, respectively. Intraclass and repeatability coefficients for MBFCS were 0.95 (CI 0.90; 0.95) and 5 mL/min/100 g. In Bland-Altman analysis, mean bias at rest was -1.1 mL/min/100 g (CI -3.1; 0.9) with limits of agreement of -27 and 24.8 mL/min/100 g. Mean bias at stress was 6.3 mL/min/100 g (CI -1.1; 14.1) with limits of agreement of -86.9 and 99.9. Mean bias of MPR was 0.11 (CI: -0.02; 0.23) with limits of agreement of -1.43 and 1.64. CONCLUSION: MBF may be determined from coronary sinus blood flow, with acceptable bias, but relatively large limits of agreement, against the reference of MBFDCE . LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

The impact of water exchange on estimates of myocardial extracellular volume calculated using contrast enhanced T1 measurements: A preliminary analysis in patients with severe aortic stenosis.

PURPOSE: Guidelines recommend measuring myocardial extracellular volume (ECV) using T1 -mapping before and 10-30 min after contrast agent administration. Data are then analyzed using a linear model (LM), which assumes fast water exchange (WX) between the ECV and cardiomyocytes. We investigated whether limited WX influences ECV measurements in patients with severe aortic stenosis (AS). METHODS: Twenty-five patients with severe AS and 5 healthy controls were recruited. T1 measurements were made on a 3 T Siemens system using a multiparametric saturation-recovery single-shot acquisition (a) before contrast; (b) 4 min post 0.05 mmol/kg gadobutrol; and (c) 4 min, (d) 10 min, and (e) 30 min after an additional gadobutrol dose (0.1 mmol/kg). Three LM-based ECV estimates, made using paired T1 measurements (a and b), (a and d), and (a and e), were compared to ECV estimates made using all 5 T1 measurements and a two-site exchange model (2SXM) accounting for WX. RESULTS: Median (range) ECV estimated using the 2SXM model was 25% (21%-39%) for patients and 26% (22%-29%) for controls. ECV estimated in patients using the LM at 10 min following a cumulative contrast dose of 0.15 mmol/kg was 21% (17%-32%) and increased significantly to 22% (19%-35%) at 30 min (p = 0.0001). ECV estimated using the LM was highest following low dose gadobutrol, 25% (19%-38%). CONCLUSION: Current guidelines on contrast agent dose for ECV measurements may lead to underestimated ECV in patients with severe AS because of limited WX. Use of a lower contrast agent dose may mitigate this effect.

"What we talk about is creating a probability": Exploring the interaction between the anticipation and decision-making processes of professional bowlers and batters in Twenty20 cricket.

Expert performers in time constrained sports use a range of information sources to facilitate anticipatory and decision-making processes. However, research has often focused on responders such as batters, goalkeepers, defenders, and returners of serve, and failed to capture the complex interaction between opponents, where responders can also manipulate probabilities in their favour. This investigation aimed to explore the interaction between top order batters and fast or medium paced bowlers in cricket and the information they use to inform their anticipatory and decision-making skills in Twenty20 competition. Eleven professional cricketers were interviewed (8 batters and 3 bowlers) using semi-structured questions and scenarios from Twenty20 matches. An inductive and deductive thematic analysis was conducted using the overarching themes of Situation Awareness (SA) and Option Awareness (OA). Within SA, the sub-themes identified related to information sources used by bowlers and batters (i.e., stable contextual information, dynamic contextual information, kinematic information). Within OA, the sub-themes identified highlighted how cricketers use these information sources to understand the options available and the likelihood of success associated with each option (e.g., risk and reward, personal strengths). A sub-theme of 'responder manipulation' was also identified within OA to provide insight into how batters and bowlers interact in a cat-and-mouse like manner to generate options that manipulate one another throughout the competition. A schematic has been developed based on the study findings to illustrate the complex interaction between the anticipation and decision-making processes of professional top order batters and fast or medium paced bowlers in Twenty20 cricket.

AMPK Regulates Phagophore-to-Autophagosome Maturation.

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation. Autophagy can be activated by nutrient stress, for example by a reduction in the cellular levels of amino acids. In contrast, how autophagy is regulated by low cellular ATP levels via the AMP-activated protein kinase (AMPK), an important therapeutic target, is less clear. Using live-cell imaging and an automated image analysis pipeline, we systematically dissect how nutrient starvation regulates autophagosome biogenesis. We demonstrate that glucose starvation downregulates autophagosome maturation by AMPK mediated inhibition of phagophores tethering to donor membranes. Our results clarify AMPK's regulatory role in autophagy and highlight its potential as a therapeutic target to reduce autophagy.

Identification of non-ischaemic fibrosis in male veteran endurance athletes, mechanisms and association with premature ventricular beats.

Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p < 0.0001) and lower rest myocardial blood flow (MBF, 0.5 ± 0.1 vs. 0.6 ± 0.1 ml/g/min, p < 0.0001). On 24-h ECG, athletes with fibrosis had greater burden of premature ventricular beats (0.3 ± 0.6 vs. 0.05 ± 0.2%, p = 0.03), with higher prevalence of ventricular couplets and triplets (33 vs. 8%, p = 0.02). In veteran endurance athletes, myocardial fibrosis is common and associated with an increased burden of ventricular ectopy. Possible mechanisms include inflammation and blood pressure. Further studies are needed to establish whether fibrosis increases risk of malignant arrhythmic events.

The effects of an acute bout of ergometer cycling on young adults' executive function: A systematic review and meta-analysis.

Purpose: The extent to which acute exercise improves executive function (EF) remains indeterminate. The purpose of this systematic review and meta-analysis was to determine the effect of acute ergometer cycling exercise on executive function (EF), including the potential moderating effects of exercise intensity and duration, EF task type, and EF task onset. Methods: We searched seven electronic research databases using cycling- and cognition-related terms. All 17 studies included were published in the last 10 years and comprised healthy participants aged 18-35 years who completed tasks assessing a variety of EFs before and after cycling exercise lasting 10-60 min. We analyzed 293 effect sizes obtained from 494 individuals (mean age = 22.07 ± 2.46 yrs). Additional analyses were performed, using averaged effect sizes for each separate study to examine the omnibus effect across studies. Results: There was a positive effect of acute ergometer cycling exercise on response time (RT) in 16 of 17 studies reviewed and a positive effect for response accuracy (RA) in 8 of 14 studies; three studies did not report RA data. Hedges' g effect sizes [95% CI] for RT ranged from 0.06 [-0.45, 0.56] to 1.50 [0.58, 2.43] and for RA from -1.94 [-2.61, -1.28] to 1.03 [0.88, 1.19].Bouts of cycling completed at moderate intensities appear to have the greatest effect on RT (Hedges' g = 1.03 [0.88, 1.19]) but no significant effect on RA; bouts with durations of 21-30 min appear to offer the greatest benefits for both RT (Hedges' g = 0.77 [0.41, 1.13]) and RA (Hedges' g = 0.92 [0.31, 1.52]). Effect sizes were greatest for RT in inhibitory control tasks (Hedges' g = 0.91 [0.80, 1.03]) and for RT when EF tasks were completed immediately post-exercise (Hedges' g = 1.11 [0.88, 1.33]). Findings were similar in the omnibus analyses: moderate-intensity bouts had the greatest effect on RT, SMD = 0.79 (95% CI [0.49, 1.08]), z = 5.20, p < 0.0001, as did cycling durations of 21-30 min, SMD = 0.87 (95% CI [0.58, 1.15], z = 5.95, p < 0.0001. The greatest benefits were derived for inhibitory control tasks, SMD = 0.70 (95% CI [0.43, 0.98]), z = 5.07, p < 0.04, and when the EF task was completed immediately post-exercise, SMD = 0.96 (95% CI [0.51, 1.41]), z = 4.19, p < 0.001. There were no overall effects on RA. Conclusion: Our findings indicate that acute bouts of cycling exercise may be a viable means to enhance RTs in immediately subsequent EF task performance, but moderating and interactive effects of several exercise parameters must also be considered.

The role and potential of using quantitative MRI biomarkers for imaging guidance in brain cancer radiotherapy treatment planning: A systematic review.

Background and purpose: Improving the accuracy of brain tumour radiotherapy (RT) treatment planning is important to optimise patient outcomes. This systematic review investigates primary studies providing clinical evidence for the integration of quantitative magnetic resonance imaging (qMRI) biomarkers and MRI radiomics to optimise brain tumour RT planning. Materials and methods: PubMed, Scopus, Embase and Web of Science databases were searched for all years until June 21, 2022. The search identified original articles demonstrating clinical evidence for the use of qMRI biomarkers and MRI radiomics for the optimization of brain cancer RT planning. Relevant information was extracted and tabulated, including qMRI metrics and techniques, impact on RT plan optimization and changes in target and normal tissue contouring and dose distribution. Results: Nineteen articles met the inclusion criteria. Studies were grouped according to the qMRI biomarkers into: 1) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI; five studies); 2) diffusion tensor imaging (DTI; seven studies); and 3) MR spectroscopic imaging (MRSI; seven studies). No relevant MRI-based radiomics studies were identified. Integration of DTI maps offers the potential for improved organs at risk (OAR) sparing. MRSI metabolic maps are a promising technique for improving delineation accuracy in terms of heterogeneity and infiltration, with OAR sparing. No firm conclusions could be drawn regarding the integration of DWI metrics and PWI maps. Conclusions: Integration of qMRI metrics into RT planning offers the potential to improve delineation and OAR sparing. Clinical trials and consensus guidelines are required to demonstrate the clinical benefits of such approaches.

Tracking the transition from an ATG9A vesicle to an autophagosome.

ABBREVIATIONS: ATG: autophagy-related proteins; ULK1/2: Unc-51-Like activating Kinases; PI3Ks: Phosphoinositide 3-Kinases; ATG2A: autophagy-related protein 2A; ATG5: autophagy-related protein 5; ATG16: autophagy-related protein 16; ATG8: autophagy-related protein 8; U2OS: human bone osteosarcoma epithelial cell; LC3B: microtubule-associated protein 1A/1B Light Chain 3B; GABARAPL1: GABA type A Receptor-Associated Protein Like 1; ATG9A: autophagy-related protein 9A; ATG13: autophagy-related protein 13; SQSTM1: Sequestosome-1/p62; WIPI2: WD repeat domain, Phosphoinositide Interacting 2; PI3P: Phosphoinositide-3-phosphate.

Systematic analysis of the molecular and biophysical properties of key DNA damage response factors.

Repair of DNA double strand breaks (DSBs) is integral to preserving genomic integrity. Therefore, defining the mechanisms underlying DSB repair will enhance our understanding of how defects in these pathways contribute to human disease and could lead to the discovery of new approaches for therapeutic intervention. Here, we established a panel of HaloTagged DNA damage response factors in U2OS cells which enables concentration-dependent protein labeling by fluorescent HaloTag ligands. Genomic insertion of HaloTag at the endogenous loci of these repair factors preserves expression levels and proteins retain proper subcellular localization, foci-forming ability, and functionally support DSB repair. We systematically analyzed total cellular protein abundance, measured recruitment kinetics to laser-induced DNA damage sites, and defined the diffusion dynamics and chromatin binding characteristics by live-cell single-molecule imaging. Our work demonstrates that the Shieldin complex, a critical factor in end-joining, does not exist in a preassembled state and that relative accumulation of these factors at DSBs occurs with different kinetics. Additionally, live-cell single-molecule imaging revealed the constitutive interaction between MDC1 and chromatin mediated by its PST repeat domain. Altogether, our studies demonstrate the utility of single-molecule imaging to provide mechanistic insights into DNA repair, which will serve as a powerful resource for characterizing the biophysical properties of DNA repair factors in living cells.

Factors affecting decision-making in Gaelic Football: a focus group approach.

Objectives: Research examining decision-making in sports has predominantly used experimental approaches that fail to provide a holistic understanding of the various factors that impact the decision-making process. The current study aimed to explore the decision-making processes of Senior (expert) and Academy (near-expert) Gaelic Football players using a focus group approach. Methods: Four focus groups were conducted; two with Senior players (n = 5; n = 6) and two with U17 Academy players (n = 5; n = 6). In each focus group, short video clips of Senior Gaelic football games were played, and the action was paused at key moments. The group then discussed the options available to the player in possession, the decision they would make in that situation, and importantly, what factors influenced the final decision. Thematic analysis was used to identify themes that emerged from the focus groups. Results and discussion: Four primary themes emerged that affected the decision-making process. Three themes were related to information sources, namely, pre-match context (coach tactics and instructions, match importance, and opposition status), current match context (score and time remaining), and visual information (player positioning and field space, and visual search strategy), and the fourth theme related to individual differences (self-efficacy, risk propensity, perceived pressure, physical characteristics, action capabilities, fatigue) that moderated the decision-making process. Compared to the near-expert Academy players, the expert Senior players displayed a more sophisticated understanding of the various sources of information and were able to integrate them in a more complex manner to make projections regarding future scenarios. For both groups, the decision-making process was moderated by individual differences. A schematic has been developed based on the study findings in an attempt to illustrate the hypothesized decision-making process.

Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation.

Autophagy is a catabolic pathway required for the recycling of cytoplasmic materials. To define the mechanisms underlying autophagy it is critical to quantitatively characterize the dynamic behavior of autophagy factors in living cells. Using a panel of cell lines expressing HaloTagged autophagy factors from their endogenous loci, we analyzed the abundance, single-molecule dynamics, and autophagosome association kinetics of autophagy proteins involved in autophagosome biogenesis. We demonstrate that autophagosome formation is inefficient and ATG2-mediated tethering to donor membranes is a key commitment step in autophagosome formation. Furthermore, our observations support the model that phagophores are initiated by the accumulation of autophagy factors on mobile ATG9 vesicles, and that the ULK1 complex and PI3-kinase form a positive feedback loop required for autophagosome formation. Finally, we demonstrate that the duration of autophagosome biogenesis is ∼110 s. In total, our work provides quantitative insight into autophagosome biogenesis and establishes an experimental framework to analyze autophagy in human cells.

The independent association of myocardial extracellular volume and myocardial blood flow with cardiac diastolic function in patients with type 2 diabetes: a prospective cross-sectional cohort study.

BACKGROUND: Diffuse myocardial fibrosis and microvascular dysfunction are suggested to underlie cardiac dysfunction in patients with type 2 diabetes, but studies investigating their relative impact are lacking. We aimed to study imaging biomarkers of these and hypothesized that fibrosis and microvascular dysfunction would affect different phases of left ventricular (LV) diastole. METHODS: In this cross-sectional study myocardial blood flow (MBF) at rest and adenosine-stress and perfusion reserve (MPR), as well as extracellular volume fraction (ECV), were determined with cardiovascular magnetic resonance (CMR) imaging in 205 patients with type 2 diabetes and 25 controls. Diastolic parameters included echocardiography-determined lateral e' and average E/e', and CMR-determined (rest and chronotropic-stress) LV early peak filling rate (ePFR), LV peak diastolic strain rate (PDSR), and left atrial (LA) volume changes. RESULTS: In multivariable analysis adjusted for possible confounders including each other (ECV for blood flow and vice versa), a 10% increase of ECV was independently associated with ePFR/EDV (rest: ß = - 4.0%, stress: ß = - 7.9%), LAmax /BSA (rest: ß = 4.8%, stress: ß = 5.8%), and circumferential (ß = - 4.1%) and radial PDSR (ß = 0.07%/sec). A 10% stress MBF increase was associated with lateral e' (ß = 1.4%) and average E/e' (ß = - 1.4%) and a 10% MPR increase to lateral e' (ß = 2.7%), and average E/e' (ß = - 2.8%). For all the above, p < 0.05. No associations were found with longitudinal PDSR or left atrial total emptying fraction. CONCLUSION: In patients with type 2 diabetes, imaging biomarkers of microvascular dysfunction and diffuse fibrosis impacts diastolic dysfunction independently of each other. Microvascular dysfunction primarily affects early left ventricular relaxation. Diffuse fibrosis primarily affects diastasis. Trial registration https://www. CLINICALTRIALS: gov . Unique identifier: NCT02684331. Date of registration: February 18, 2016.

Comprehensive Neonatal Cardiac, Feed and Wrap, Non-contrast, Non-sedated, Free-breathing Compressed Sensing 4D Flow MRI Assessment.

BACKGROUND: Cardiac MRI is an important imaging tool in congenital cardiac disease, but its use has been limited in the neonatal population as general anesthesia has been needed for breath-holding. Technological advances in four-dimensional (4D) flow MRI have now made nonsedated free-breathing acquisition protocols a viable clinical option, but the method requires prospective validation in neonates. PURPOSE: To test the feasibility of compressed sensing (CS) 4D flow MRI in the neonatal population and to compare with standard previously validated two-dimensional (2D) phase-contrast (PC) flow MRI. STUDY TYPE: Prospective, cohort, image quality. POPULATION: A total of 14 healthy neonates (median [range] age: 2.5 [0-80] days; 8 male). FIELD STRENGTH AND SEQUENCE: Noncontrast 2D cine gradient echo sequence with through-plane velocity encoding (PC) sequence and compressed sensing (CS) three-dimensional (3D), time-resolved, cine phase-contrast MRI with 3D velocity-encoding (4D flow MRI) at 3 T. ASSESSMENT: Aortic 2D PC, and aortic, pulmonary trunk and superior vena cava CS 4D flow MRI were acquired using the feed and wrap technique (nonsedated) and quantified using commercially available software. Aortic flow and peak velocity were compared between methods. Internal consistency of 4D flow MRI was determined by comparing mean forward flow of the main pulmonary artery (MPA) vs. the sum of left and right pulmonary artery flows (LPA and RPA) and by comparing mean ascending aorta forward flow (AAo) vs. the sum of superior vena cava (SVC) and descending aorta flows (DAo). STATISTICAL TESTS: Flow and peak-velocity comparisons were assessed using paired t-tests, with P < 0.05 considered significant, and Bland-Altman analysis. Interobserver and intraobserver agreement and internal consistency were analyzed by intraclass correlation co-efficient (ICC). RESULTS: There was no statistically significant difference between ascending aortic forward flow between 2D PC and CS 4D Flow MRI (P = 0.26) with a bias of 0.11 mL (-0.59 to 0.82 mL) nor peak velocity (P = 0.11), with a bias of -5 cm/sec and (-26 to 16 cm/sec). There was excellent interobserver and intraobserver agreement for each vessel (interobserver ICC: AAo 1.00; DAo 0.94, SVC 0.90, MPA 0.99, RPA 0.98, LPA 0.96; intraobserver ICC: AAo 1.00; DAo 0.99, SVC 0.98, MPA 1.00, RPA 1.00, LPA 0.99). Internal consistency measures showed excellent agreement for both mean forward flow of main pulmonary artery vs. the sum of left and right pulmonary arteries (ICC: 0.95) and mean ascending aorta forward flow vs. the sum of superior vena cava and descending aorta flows (ICC: 1.00). CONCLUSION: Sedation-free neonatal feed and wrap MRI is well tolerated and feasible. CS 4D flow MRI quantification is similar to validated 2D PC free-breathing imaging with excellent interobserver and intraobserver agreement. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Sex- and age-specific normal values for automated quantitative pixel-wise myocardial perfusion cardiovascular magnetic resonance.

AIMS: Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers. METHODS AND RESULTS: A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = -0.43, P < 0.001 and r = -0.34, P < 0.001, respectively). CONCLUSION: Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use.

Skill-Based Differences in the Detection and Utilization of Opponent Action Preferences Following Increasing Exposure and Changes in Tendencies.

We examined skill-based differences in the detection and utilization of contextual information over a period of increasing exposure to an opponent's action preferences in soccer. Moreover, we investigated the ability of athletes to adapt to changes in these action preferences over time. In an initial detection phase, the attacking opponent demonstrated a proclivity to either pass or dribble, with these preferences being reversed in a subsequent adaptation phase of the same length. Skilled soccer players showed superior anticipation accuracy across both phases compared with less-skilled counterparts. The skilled participants significantly enhanced their performance over both phases, despite a significant drop in performance immediately following the change in opponent action preferences. In contrast, the less-skilled group only improved over the detection phase. Gaze data revealed that the skilled participants fixated more on kinematically relevant areas, compared with the less-skilled group, and increased the time spent fixating the player "off the ball" following greater volumes of exposure. Our novel findings elaborate on how skilled performers use both action preferences and motion information to anticipate an opponent's impending actions in sport.

An Active Inference Account of Skilled Anticipation in Sport: Using Computational Models to Formalise Theory and Generate New Hypotheses.

Optimal performance in time-constrained and dynamically changing environments depends on making reliable predictions about future outcomes. In sporting tasks, performers have been found to employ multiple information sources to maximise the accuracy of their predictions, but questions remain about how different information sources are weighted and integrated to guide anticipation. In this paper, we outline how predictive processing approaches, and active inference in particular, provide a unifying account of perception and action that explains many of the prominent findings in the sports anticipation literature. Active inference proposes that perception and action are underpinned by the organism's need to remain within certain stable states. To this end, decision making approximates Bayesian inference and actions are used to minimise future prediction errors during brain-body-environment interactions. Using a series of Bayesian neurocomputational models based on a partially observable Markov process, we demonstrate that key findings from the literature can be recreated from the first principles of active inference. In doing so, we formulate a number of novel and empirically falsifiable hypotheses about human anticipation capabilities that could guide future investigations in the field.