Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study.

BACKGROUND: Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. METHODS: We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves. RESULTS: Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP. CONCLUSIONS: PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

Towards near-term quantum simulation of materials.

Determining the ground and excited state properties of materials is considered one of the most promising applications of quantum computers. On near-term hardware, the limiting constraint on such simulations is the requisite circuit depths and qubit numbers, which currently lie well beyond near-term capabilities. Here we develop a quantum algorithm which reduces the estimated cost of material simulations. For example, we obtain a circuit depth improvement by up to 6 orders of magnitude for a Trotter layer of time-dynamics simulation in the transition-metal oxide SrVO3 compared with the best previous quantum algorithms. We achieve this by introducing a collection of connected techniques, including highly localised and physically compact representations of materials Hamiltonians in the Wannier basis, a hybrid fermion-to-qubit mapping, and an efficient circuit compiler. Combined together, these methods leverage locality of materials Hamiltonians and result in a design that generates quantum circuits with depth independent of the system's size. Although the requisite resources for the quantum simulation of materials are still beyond current hardware, our results show that realistic simulation of specific properties may be feasible without necessarily requiring fully scalable, fault-tolerant quantum computers, providing quantum algorithm design incorporates deeper understanding of the target materials and applications.

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.

Early prediction of left ventricular function improvement in patients with new-onset heart failure and presumed non-ischaemic aetiology.

OBJECTIVES: To determine baseline characteristics predictive of left ventricular ejection fraction (LVEF) recovery in patients diagnosed with heart failure with reduced ejection fraction (HFrEF) and presumed non-ischaemic aetiology. METHODS: We prospectively recruited patients who were diagnosed with HFrEF (LVEF ≤40%) on echocardiography and subsequently underwent cardiac MRI. Patients were excluded if they had a known history of coronary artery disease (>70% on invasive coronary angiography), myocardial infarction, coronary revascularisation or anginal symptoms. At cardiac MRI assessment, patients were categorised as either ongoing HFrEF or heart failure with improved ejection fraction (HFimpEF, LVEF >40% with ≥10% of absolute improvement). Clinical characteristics were compared between the groups. Logistic regression was performed to identify variables that were associated with LVEF recovery. Optimal cut-offs in QRISK3 score and baseline LVEF for prediction of LVEF recovery were identified through receiver operating characteristic curve analysis. RESULTS: A total of 407 patients were diagnosed with HFrEF, and 139 (34%) attained HFimpEF at cardiac MRI assessment (median 63 days, IQR 41-119 days). Mean age of the patients was 63±12 years, and 260 (63.9%) were male. At multivariate logistic regression, both QRISK3 score (HR 0.978; 95% CI 0.963 to 0.993, p=0.004) and baseline LVEF (HR 1.044; 95% CI 1.015 to 1.073, p=0.002) were independent predictors of HFimpEF. Among patients with baseline LVEF ≤25%, only 22 (21.8%) recovered. In patients with baseline LVEF 25-40%, QRISK3 score >18% was associated with lack of recovery (HR 2.75; 95% CI 1.70 to 4.48, p<0.001). Additionally, QRISK3 score was associated with the presence of ischaemic late gadolinium enhancement (HR 1.035; 95% CI 1.018 to 1.053, p<0.001). CONCLUSIONS: The QRISK3 score helps identify patients with HFrEF with undiagnosed vascular disease. Patients with either a very low baseline LVEF or a high QRISK3 score have less chance of left ventricular recovery and should be prioritised for early cardiac MRI and close monitoring.

Cardiac magnetic resonance left ventricular filling pressure is linked to symptoms, signs and prognosis in heart failure.

AIMS: Left ventricular filling pressure (LVFP) can be estimated from cardiovascular magnetic resonance (CMR). We aimed to investigate whether CMR-derived LVFP is associated with signs, symptoms, and prognosis in patients with recently diagnosed heart failure (HF). METHODS AND RESULTS: This study recruited 454 patients diagnosed with HF who underwent same-day CMR and clinical assessment between February 2018 and January 2020. CMR-derived LVFP was calculated, as previously, from long- and short-axis cines. CMR-derived LVFP association with symptoms and signs of HF was investigated. Patients were followed for median 2.9 years (interquartile range 1.5-3.6 years) for major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, HF hospitalization, non-fatal stroke, and non-fatal myocardial infarction. The mean age was 62 ± 13 years, 36% were female (n = 163), and 30% (n = 135) had raised LVFP. Forty-seven per cent of patients had an ejection fraction < 40% during CMR assessment. Patients with raised LVFP were more likely to have pleural effusions [hazard ratio (HR) 3.2, P = 0.003], orthopnoea (HR 2.0, P = 0.008), lower limb oedema (HR 1.7, P = 0.04), and breathlessness (HR 1.7, P = 0.01). Raised CMR-derived LVFP was associated with a four-fold risk of HF hospitalization (HR 4.0, P < 0.0001) and a three-fold risk of MACE (HR 3.1, P < 0.0001). In the multivariable model, raised CMR-derived LVFP was independently associated with HF hospitalization (adjusted HR 3.8, P = 0.0001) and MACE (adjusted HR 3.0, P = 0.0001). CONCLUSIONS: Raised CMR-derived LVFP is strongly associated with symptoms and signs of HF. In addition, raised CMR-derived LVFP is independently associated with subsequent HF hospitalization and MACE.

Protein hydrolysate versus standard formula for preterm infants.

BACKGROUND: When human milk is not available for feeding preterm infants, protein hydrolysate, rather than standard cow's milk formulas (with intact proteins), is often used because it is perceived as being tolerated better and less likely to lead to complications. However, protein hydrolysate formulas are more expensive than standard formulas, and concern exists that their use in practice is not supported by high-quality evidence. OBJECTIVES: To assess the effects of feeding preterm infants hydrolysed formula (vs standard cow's milk formula) on risk of feed intolerance, necrotising enterocolitis, and other morbidity and mortality. SEARCH METHODS: We used the standard Cochrane Neonatal search strategy including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1), in the Cochrane Library; Ovid MEDLINE (1966 to 28 January 2019); Ovid Embase (1980 to 28 January 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (28 January 2019), as well as conference proceedings and previous reviews. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared feeding preterm infants protein hydrolysate versus standard (non-hydrolysed) cow's milk formula. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in sensitivity analyses. We assessed quality of evidence at the outcome level using the GRADE approach. MAIN RESULTS: We identified 11 trials for inclusion in the review. All trials were small (total participants 665) and had various methodological limitations including uncertainty about methods to ensure allocation concealment and blinding. Most participants were clinically stable preterm infants of less than about 34 weeks' gestational age or with birth weight less than about 1750 g. Fewer participants were extremely preterm, extremely low birth weight, or growth restricted. Most trials found no effects on feed intolerance, assessed variously as mean pre-feed gastric residual volume, incidence of abdominal distension or other gastrointestinal signs of concern, or time taken to achieve full enteral feeds (meta-analysis was limited because studies used different measures). Meta-analysis showed no effect on the risk of necrotising enterocolitis (typical risk ratio 1.10, 95% CI 0.36 to 3.34; risk difference 0.00, 95% CI -0.03 to 0.04; 5 trials, 385 infants) (low-certainty evidence; downgraded for imprecision and design weaknesses). AUTHORS' CONCLUSIONS: The identified trials provide only low-certainty evidence about the effects of feeding preterm infants protein hydrolysate versus standard formula. Existing data do not support conclusions that feeding protein hydrolysate affects the risk of feed intolerance or necrotising enterocolitis. Additional large, pragmatic trials are needed to provide more reliable and precise estimates of effectiveness and cost-effectiveness.

Self-efficacy beliefs of medical students: a critical review.

INTRODUCTION: Self-efficacy is a theoretically and empirically robust motivation belief that has been shown to play an important role in the learning and development of new skills and knowledge. In this article, we critically review research on the self-efficacy beliefs of medical students, with a goal to evaluate the existing research and to strengthen future work. In particular, we sought to describe the state of research on medical student self-efficacy and to critically examine the conceptualization and measurement of the construct. Finally, we aimed to provide directions for future self-efficacy research. METHODS: We critically reviewed 74 published articles that included measures of self-efficacy beliefs of medical students. RESULTS: Our review showed that (a) research on the self-efficacy beliefs of medical students is growing and is becoming increasingly international, and (b) that nearly half (46%) of self-efficacy measures showed conceptual and operational flaws. DISCUSSION: Our critical review of 74 research studies on self-efficacy of medical students found that although research in the field is increasing, nearly half of measures labelled as self-efficacy were incongruent with the conceptual guidelines set by self-efficacy experts. We provide five suggestions for future research on the self-efficacy of medical students.

Protein hydrolysate versus standard formula for preterm infants.

BACKGROUND: When human milk is not available for feeding preterm infants, protein hydrolysate rather than standard cow's milk formulas (with intact proteins) are often used because they are perceived as being tolerated better and less likely to lead to complications. However, protein hydrolysate formulas are more expensive than standard formulas, and concern exists that their use in practice is not supported by high-quality evidence. OBJECTIVES: To assess the effect of feeding preterm infants with hydrolysed formula (versus standard cow's milk formulas) on the risk of feed intolerance, necrotising enterocolitis, and other morbidity and mortality in preterm infants. SEARCH METHODS: We used the standard Cochrane Neonatal search strategy including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4), Ovid MEDLINE, Ovid Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (to April 2017), as well as conference proceedings and previous reviews. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared feeding preterm infants with protein hydrolysate versus standard (non-hydrolysed) cow's milk formula. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in sensitivity analyses. We assessed quality of evidence at the outcome level using the GRADE approach. MAIN RESULTS: We identified 11 trials for inclusion in the review. All trials were small (total participants 665) and had various methodological limitations including uncertainty about methods to ensure allocation concealment and blinding. Most participants were clinically stable preterm infants of gestational age less than about 34 weeks or birth weight less than about 1750 g. Fewer participants were extremely preterm, extremely low birth weight, or growth-restricted. Most trials found no effects on feed intolerance assessed variously as mean prefeed gastric residual volume, incidence of abdominal distention or other concerning gastrointestinal signs, or time taken to achieve full enteral feeds (meta-analysis was limited because studies used different measures). Meta-analysis found no effect on the risk of necrotising enterocolitis (typical risk ratio 1.10, 95% CI 0.36 to 3.34; risk difference 0.00, 95% CI -0.03 to 0.04; 5 trials, 385 infants) (low quality evidence; downgraded for imprecision and design weaknesses). AUTHORS' CONCLUSIONS: The identified trials provide only low quality evidence about the effects of feeding preterm infants with protein hydrolysate versus standard formula. The existing data did not support conclusions that feeding with protein hydrolysate affects the risk of feed intolerance or necrotising enterocolitis. Further large, pragmatic trials are needed to provide more reliable and precise estimates of effectiveness and cost-effectiveness.

Quantum State Tomography via Reduced Density Matrices.

Quantum state tomography via local measurements is an efficient tool for characterizing quantum states. However, it requires that the original global state be uniquely determined (UD) by its local reduced density matrices (RDMs). In this work, we demonstrate for the first time a class of states that are UD by their RDMs under the assumption that the global state is pure, but fail to be UD in the absence of that assumption. This discovery allows us to classify quantum states according to their UD properties, with the requirement that each class be treated distinctly in the practice of simplifying quantum state tomography. Additionally, we experimentally test the feasibility and stability of performing quantum state tomography via the measurement of local RDMs for each class. These theoretical and experimental results demonstrate the advantages and possible pitfalls of quantum state tomography with local measurements.

Topological degeneracy (Majorana zero-mode) and 1 + 1D fermionic topological order in a magnetic chain on superconductor via spontaneous Z2(f) symmetry breaking.

We study a chain of ferromagnetic sites, ie nano-particles, molecules or atoms, on a substrate of fully gapped superconductors. We find that under quite realistic conditions, the fermion-number-parity symmetry Z2(f) can spontaneously break. In other words, such a chain can realize a 1 + 1D fermionic topologically ordered state and the corresponding two-fold topological degeneracy on an open chain. Such a topological degeneracy becomes the so called Majorana zero mode in the non-interacting limit.