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Abstract We present the first determination of the topological susceptibility from lattice QCD in the presence of strong background magnetic fields. Our simulations employ 2+1 flavours of stout-improved staggered quarks with physical masses and cover a broad range of temperatures and magnetic field values. The results are extrapolated to the continuum limit using four different lattice spacings and an eigenvalue reweighting technique to reduce discretisation errors. For low temperatures, our calculations show an enhancement of the topological susceptibility due to the magnetic field, compatible with predictions from chiral perturbation theory. At high temperatures, we observe the impact of inverse magnetic catalysis on the susceptibility.

Abstract In this paper we investigate the chiral magnetic effect (CME): the generation of an electric current due to a homogeneous background magnetic field and a homogeneous chiral imbalance in QCD. We demonstrate that the leading coefficient describing the CME vanishes in equilibrium, both for free fermions as well as in full QCD. Our full QCD results are based on continuum extrapolated lattice simulations using dynamical staggered quarks with physical masses as well as quenched Wilson quarks. We show that it is crucial that a gauge invariant ultraviolet regularization is used to compute the CME and elaborate on why some of the existing in-equilibrium calculations of this effect gave a nonzero result. We stress that our findings imply the absence of a time-independent CME current flowing in equilibrium QCD, but do not concern the CME as an out-of-equilibrium, time-dependent effect.

This quasi-experimental study aimed to examine content-area literacy instruction in comparison to a science-infused literacy instruction (SILI) to determine how these two approaches influenced 2nd grade students' ability to read and write science informational text and the students' attitude and motivation towards reading. After professional development, five teachers taught their classes twelve thematic lessons designed using either the content-area literacy (N = 37) or the SILI (N = 40) instruction to 2nd grade students. Teachers in both groups implemented thematic lessons that taught the life cycle of plants and included interactive read-alouds, graphic organizers, watching time lapse videos of plant growth, and reading digital texts independently and in small groups to support students in building the content knowledge and vocabulary necessary to write science informational texts. Students in the SILI group also participated in hands-on science activities including planting seeds and documenting plant growth, exploring the parts of a live basil plant, and taking walks outdoors to observe plants at various stages of the plant life cycle. Lessons took place over four weeks to assist students in acquiring science content knowledge so as to transfer this knowledge into science informational texts and to determine the influence of both instructional approaches on reading comprehension and reading attitude and motivation. Findings resulted in the content-area literacy instruction producing higher and statistically significant reading comprehension and writing rubric scores than the SILI group with medium effect sizes reported. The SILI group produced higher reading attitude and motivation scores, but these results were not statistically significant. Implications for both early childhood science and literacy classroom instruction as well as multiple implications for future research are discussed.

Abstract In this paper we study the emergence of steady electric currents in QCD as a response to a non-uniform magnetic background using lattice simulations with 2 + 1 quark flavors at the physical point, as well as leading-order chiral perturbation theory. Using these currents, we develop a novel method to determine the leading-order coefficient of the equation of state in a magnetic field expansion: the magnetic susceptibility of the QCD medium. We decompose the current expectation value into valence- and sea-quark contributions and demonstrate that the dominant contribution to the electric current is captured by the valence term alone, allowing for a comparably cheap determination of the susceptibility. Our continuum extrapolated lattice results for the equation of state confirm the findings of some of the existing studies in the literature, namely that the QCD medium behaves diamagnetically at low and paramagnetically at high temperatures.

Abstract In this paper we study the Chiral Separation Effect by means of first-principles lattice QCD simulations. For the first time in the literature, we determine the continuum limit of the associated conductivity using 2+1 flavors of dynamical staggered quarks at physical masses. The results reveal a suppression of the conductivity in the confined phase and a gradual enhancement toward the perturbative value for high temperatures. In addition to our dynamical setup, we also investigate the impact of the quenched approximation on the conductivity, using both staggered and Wilson quarks. Finally, we highlight the relevance of employing conserved vector and anomalous axial currents in the lattice simulations.

Abstract Off-central heavy-ion collisions are known to feature magnetic fields with magnitudes and characteristic gradients corresponding to the scale of the strong interactions. In this work, we employ equilibrium lattice simulations of the underlying theory, QCD, involving similar inhomogeneous magnetic field profiles to achieve a better understanding of this system. We simulate three flavors of dynamical staggered quarks with physical masses at a range of magnetic fields and temperatures, and extrapolate the results to the continuum limit. Analyzing the impact of the field on the quark condensate and the Polyakov loop, we find non-trivial spatial features that render the QCD medium qualitatively different as in the homogeneous setup, especially at temperatures around the transition. In addition, we construct leading-order chiral perturbation theory for the inhomogeneous background and compare its prediction to our lattice results at low temperature. Our findings will be useful to benchmark effective theories and low-energy models of QCD for a better description of peripheral heavy-ion collisions.

Abstract We determine the QCD equation of state at nonzero temperature in the presence of an isospin asymmetry between the light quark chemical potentials on the lattice. Our simulations employ N f = 2 + 1 flavors of dynamical staggered quarks at physical masses, using three different lattice spacings. The main results, obtained at the individual lattice spacings, are based on a two-dimensional spline interpolation of the isospin density, from which all relevant quantities can be obtained analytically. In particular, we present results for the pressure, the interaction measure, the energy and entropy densities, as well as the speed of sound. Remarkably, the latter is found to exceed its ideal gas limit deep in the pion condensed phase, the first account of the violation of this limit in first principles QCD. Finally, we also compute the phase diagram in the temperature — isospin density plane for the first time. Even though the results are not continuum extrapolated and thus not final, the data for all observables will be useful for the benchmarking of effective theories and low-energy models of QCD and are provided in ancillary files for simple reuse.

Summary: Background: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. Methods: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. Findings: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8–6.3), two (5.1; 3.5–7.6) and five years (4.1; 3.0–5.5) compared to baseline (16.2; 14.4–18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68–0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70–0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year−1 [0.28–0.41]). We didn't find predictive factors for effectiveness. Interpretation: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. Funding: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

IntroductionChildhood obesity has become an important topic, not only of increasing relevance during the COVID-19 pandemic but specifically enhanced by it. Restrictions implemented to mitigate further outbreaks led to major constraints on daily physical activity, leading to a severe increase in body weight among children. This study highlights changes in BMI and weight development in children during and (in particular) after the COVID-19 restrictions in Austria, focusing on various socioeconomic factors.MethodsWeight development throughout the pandemic and socioeconomic factors were evaluated by anonymous cross-sectional surveys filled out by parents at a pediatric practice.ResultsThis study included 388 children. The rate of obesity increased by 88.5%, from 6.4 to 12.1%, throughout the pandemic, reaching a maximum of 15.2% during the restrictions. Overall, age-adapted BMI z-scores increased significantly by 0.22 during the restrictions and remained increased by 0.19 compared to pre-pandemic levels. With the exception of obese children, all children in the study population experienced significant weight loss after the restrictions were lifted. Obese children continued to gain weight without any sign of the onset of normalization. Socioeconomic factors, such as participation in regular activity in the form of organized sport or the availability of an outdoor area, were associated with relevant differences before the pandemic but had no protective effect against intra-pandemic weight gain. A higher level of parental education was the only factor associated with less weight gain in children during the early phase of the pandemic.DiscussionAustrian COVID-19 restrictions have had concerning effects on pediatric BMI, with very little effect of socioeconomic background. After restrictions were loosened, measurable weight loss occurred, but the significant increase in children's BMI percentiles persisted. No weight loss was observed among children who were obese prior to the pandemic. There is a need for broad projects tackling childhood obesity, as obese children are the most vulnerable group with the strongest and most severe long-term effects.

Abstract Background To compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls. Methods We performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression. Results The questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression. Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood–derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

For large isospin asymmetries, perturbation theory predicts the quantum chromodynamic (QCD) ground state to be a superfluid phase of u and d ¯ Cooper pairs. This phase, which is denoted as the Bardeen-Cooper-Schrieffer (BCS) phase, is expected to be smoothly connected to the standard phase with Bose-Einstein condensation (BEC) of charged pions at μ I ≥ m π / 2 by an analytic crossover. A first hint for the existence of the BCS phase, which is likely characterised by the presence of both deconfinement and charged pion condensation, comes from the lattice observation that the deconfinement crossover smoothly penetrates into the BEC phase. To further scrutinize the existence of the BCS phase, in this article we investigate the complex spectrum of the massive Dirac operator in 2+1-flavor QCD at nonzero temperature and isospin chemical potential. The spectral density near the origin is related to the BCS gap via a generalization of the Banks-Casher relation to the case of complex Dirac eigenvalues (derived for the zero-temperature, high-density limits of QCD at nonzero isospin chemical potential).

Objectives: In critical care it is crucial to appropriately assess the risk of mortality for each patient. This is especially relevant in pediatrics, with its need for accurate and repeatable scoring. Aim of this study was to evaluate an age-adapted version of the expanded Simplified Acute Physiology Score II; (p-SAPS II), a repeatable, newly-designed scoring system compared to established scores (Pediatric Sequential Organ Failure Assessment Score/pSOFA, Pediatric Logistic Organ Dysfunction Score-2/PELOD-2 and Pediatric Index of Mortality 3/PIM3).Design: This retrospective cohort pilot study included data collected from patients admitted to the Pediatric Intensive Care Unit (PICU) at the Medical University of Vienna between July 2017 through December 2018.Patients: 231 admissions were included, comprising neonates (gestational age of ≥ 37 weeks) and patients up to 18 years of age with a PICU stay longer than 48 h.Main Outcomes: Mortality risk prediction and discrimination between survivors and non-survivors were the main outcomes of this study. The primary statistical methods for evaluating the performance of each score were the area under the receiver operating characteristic curve (AUROC) and goodness-of-fit test.Results: Highest AUROC curve was calculated for p-SAPS II (AUC = 0.86; 95% CI: 0.77–0.96; p < 0.001). This was significantly higher than the AUROCs of PELOD-2/pSOFA but not of PIM3. However, in a logistic regression model including p-SAPS II and PIM3 as covariates, p-SAPS II had a significant effect on the accuracy of prediction (p = 0.003). Nevertheless, according to the goodness-of-fit test for p-SAPS II and PIM3, p-SAPS II overestimated the number of deaths, whereas PIM3 showed acceptable estimations. Repeatability testing showed increasing AUROC values for p-SAPS II throughout the clinical stay (0.96 at day 28) but still no significant difference to PIM 3. The prediction accuracy, although improved over the days and even exceeded PIM 3.Conclusions: The newly-created p-SAPS II performed better than the established PIM3 in terms of discriminating between survivors and non-survivors. Furthermore, p-SAPS II can be assessed repeatably throughout a patient's PICU stay what improves mortality prediction. However, there is still a need to optimize calibration of the score to accurately predict mortality sooner throughout the clinical stay.

Abstract We numerically explore an alternative discretization of continuum SU(N c ) Yang-Mills theory on a Euclidean spacetime lattice, originally introduced by Budzcies and Zirnbauer for gauge group U(N c ). This discretization can be reformulated such that the self-interactions of the gauge field are induced by a path integral over N b auxiliary bosonic fields, which couple linearly to the gauge field. In the first paper of the series we have shown that the theory reproduces continuum SU(N c ) Yang-Mills theory in d = 2 dimensions if N b is larger than N c − 3 4 $$ \frac{3}{4} $$ and conjectured, following the argument of Budzcies and Zirnbauer, that this remains true for d > 2. In the present paper, we test this conjecture by performing lattice simulations of the simplest nontrivial case, i.e., gauge group SU(2) in three dimensions. We show that observables computed in the induced theory, such as the static q q ¯ $$ \overline{q} $$ potential and the deconfinement transition temperature, agree with the same observables computed from the ordinary plaquette action up to lattice artifacts. We also find evidence that the bound for N b can be relaxed to N c − 5 4 $$ \frac{5}{4} $$ as conjectured in our earlier paper. Studies of how the new discretization can be used to change the order of integration in the path integral to arrive at dual formulations of QCD are left for future work.

Abstract Ischemic heart disease is the leading cause of death worldwide. The blockade of coronary arteries limits oxygen-rich blood to the heart and consequently there is cardiomyocyte (CM) cell death, inflammation, fibrotic scarring, and myocardial remodeling. Unfortunately, current therapeutics fail to effectively replace the lost cardiomyocytes or prevent fibrotic scarring, which results in reduced cardiac function and the development of heart failure (HF) in the adult mammalian heart. In contrast, neonatal mice are capable of regenerating their hearts following injury. However, this regenerative response is restricted to the first week of post-natal development. Recently, we identified that cholinergic nerve signaling is necessary for the neonatal mouse cardiac regenerative response. This demonstrates that cholinergic nerve stimulation holds significant potential as a bioelectronic therapeutic tool for heart disease. However, the mechanisms of nerve directed regeneration in the heart remain undetermined. In this review, we will describe the historical evidence of nerve function during regeneration across species. Specifically, we will focus on the emerging role of cholinergic innervation in modulating cardiomyocyte proliferation and inflammation during heart regeneration. Understanding the role of nerves in mammalian heart regeneration and adult cardiac remodeling can provide us with innovative bioelectronic-based therapeutic approaches for treatment of human heart disease.

Chimeric antigen receptor (CAR) T cells have emerged as a promising treatment for patients with advanced B-cell cancers. However, widespread application of the therapy is currently limited by potentially life-threatening toxicities due to a lack of control of the highly potent transfused cells. Researchers have therefore developed several regulatory mechanisms in order to control CAR T cells in vivo. Clinical adoption of these control systems will depend on several factors, including the need for temporal and spatial control, the immunogenicity of the requisite components as well as whether the system allows reversible control or induces permanent elimination. Here we describe currently available and emerging control methods and review their function, advantages, and limitations.

Abstract We perform a high precision measurement of the static q q ¯ $$ q\overline{q} $$ potential in three-dimensional SU(N) gauge theory with N = 2, 3 and compare the results to the potential obtained from the effective string theory. In particular, we show that the exponent of the leading order correction in 1/R is 4, as predicted, and obtain accurate results for the continuum limits of the string tension and the non-universal boundary coefficient b ¯ 2 $$ {\overline{b}}_2 $$ , including an extensive analysis of all types of systematic uncertainties. We find that the magnitude of b ¯ 2 $$ {\overline{b}}_2 $$ decreases with increasing N, leading to the possibility of a vanishing b ¯ 2 $$ {\overline{b}}_2 $$ in the large N limit. In the standard form of the effective string theory possible massive modes and the presence of a rigidity term are usually not considered, even though they might give a contribution to the energy levels. To investigate the effect of these terms, we perform a second analysis, including these contributions. We find that the associated expression for the potential also provides a good description of the data. The resulting continuum values for b ¯ 2 $$ {\overline{b}}_2 $$ are about a factor of 2 smaller than in the standard analysis, due to contaminations from an additional 1/R 4 term. However, b ¯ 2 $$ {\overline{b}}_2 $$ shows a similar decrease in magnitude with increasing N. In the course of this extended analysis we also obtain continuum results for the masses appearing in the additional terms and we find that they are around twice as large as the square root of the string tension in the continuum and compatible between SU(2) and SU(3) gauge theory. In the follow up papers we will extend our investigations to the large N limit and excited states of the open flux tube.

Introduction Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on ‘trial and error’. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.Methods and analysis In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018–2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided)

Hypoxia, triggered in large part by eutrophication, exerts widespread and expanding stress on coastal ecosystems. Hypoxia is often specifically defined as water having dissolved oxygen (DO) concentrations < 2 mg L−1. However, DO concentration alone is insufficient to categorize hypoxic stress or predict impacts of hypoxia on zooplankton and fish. Hypoxic stress depends on the oxygen supply relative to metabolic demand. Water temperature controls both oxygen solubility and the metabolic demand of aquatic ectotherms. Accordingly, to assess impacts of hypoxia requires consideration of effects of temperature on both oxygen availability and animal metabolism. Temperature differences across ecosystems or across seasons or years within an ecosystem can dramatically impact the severity of hypoxia even at similar DO concentrations. Living under sub-optimum DO can reduce temperature-dependent metabolic efficiencies, prey capture efficiency, growth and reproductive potential, thus impacting production and individual zooplankton and fish fitness. Avoidance of hypoxic bottom water can reduce or eliminate low-temperature thermal refuges for organisms and increase energy demands and respiration rates, and potentially reduce overall fitness if alternative habitats are sub-optimal. Moreover, differential habitat shifts among species can shift predator-prey abundance ratios or interactions and thus modify food webs. For example, more tolerant zooplankton prey may use hypoxic waters as a refuge from fish predation. In contrast, zooplankton avoidance of hypoxic bottom waters can result in prey aggregations at oxyclines sought out by fish predators. Hypoxic conditions that affect spatial ecology can drive taxonomic and size shifts in the zooplankton community, affecting foraging, consumption and growth of fish. Advances in understanding the ecological effects of low DO waters on pelagic zooplankton and fish and comparisons among ecosystems will require development of generic models that estimate the oxygen demand of organisms in relation to oxygen supply which depends on both DO and temperature. We provide preliminary analysis of a metric (Oxygen Stress Level) which integrates oxygen demand in relation to oxygen availability for a coastal copepod and compare the prediction of oxygen stress to actual copepod distributions in areas with hypoxic bottom waters.