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The standard view on explicit theory of mind development holds that children around the age of 4 years start to ascribe beliefs to themselves and others, typically tested with false belief (FB) tasks. The present study (N = 95, 53 female, 41 male, Austrian, 41 to 80 months) systematically investigated the puzzling phenomenon that FB achievers (FB+) fail knowledge (often subsumed under "true belief") tasks: Despite the story protagonist witnessing the displacement of an object these children predict that the protagonist will look for it in its original location. We replicate this result in Experiment 1. Interestingly, some of our children indicated uncertainty about the protagonist's awareness of the relevant event. Thus, in Experiment 2 a new active watching condition was designed to help children understand that the protagonist attended to the critical event. This practically eradicated the knowledge error. Experiment 3 successfully replicated these results. Implications for existing explanations, perceptual access reasoning (PAR, Fabricius, Boyer, Weimer, & Carroll, 2010) and pragmatic difficulties (Oktay-Gür & Rakoczy, 2017) are discussed., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

There have been several attempts to quantify the diagnostic distortion caused by algorithms that perform low-dimensional electrocardiogram (ECG) representation. However, there is no universally accepted quantitative measure that allows the diagnostic distortion arising from denoising, compression, and ECG beat representation algorithms to be determined. Hence, the main objective of this work was to develop a framework to enable biomedical engineers to efficiently and reliably assess diagnostic distortion resulting from ECG processing algorithms. We propose a semiautomatic framework for quantifying the diagnostic resemblance between original and denoised/reconstructed ECGs. Evaluation of the ECG must be done manually, but is kept simple and does not require medical training. In a case study, we quantified the agreement between raw and reconstructed (denoised) ECG recordings by means of kappa-based statistical tests. The proposed methodology takes into account that the observers may agree by chance alone. Consequently, for the case study, our statistical analysis reports the "true", beyond-chance agreement in contrast to other, less robust measures, such as simple percent agreement calculations. Our framework allows efficient assessment of clinically important diagnostic distortion, a potential side effect of ECG (pre-)processing algorithms. Accurate quantification of a possible diagnostic loss is critical to any subsequent ECG signal analysis, for instance, the detection of ischemic ST episodes in long-term ECG recordings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib)., Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe., Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals., Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Acupuncture is a promising treatment for visceral cancer pain, but to date, evidence for immediate effects on neuropathic pain is limited., Case Presentation: This report presents a case of immediate pain relief by single-needle acupuncture on opioid-refractory neuropathic breakthrough pain in a 78-year-old female breast cancer patient with cervical bone metastases. Acupuncture was applied at a single point neuroanatomically correlating to the pain affected spinal segment., Discussion: Immediately after acupuncture, the patient reported a complete pain relief lasting for one day. In the following days, neuropathic breakthrough pain was better manageable with reduced dosages of opioids. Acupuncture is possibly effective in providing immediate and safe pain relief in neuropathic cancer pain through neuromodulating effects on the spinal and central nervous level. Randomized controlled studies with individualized acupuncture point protocols are needed to establish efficacy and safety., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Difficult-to-treat infections caused by antibiotic-susceptible strains have been linked to the occurrence of persisters, a subpopulation of dormant bacteria that tolerate antibiotic exposure despite lacking genetic resistance. These persisters can be identified phenotypically by plating on nutrient agar because of their altered growth dynamics, resulting in colony-size heterogeneity. The occurrence of within-patient bacterial phenotypic heterogeneity in various infections and clinical determinants of persister formation remains unknown., Methods: We plated bacteria derived from 132 patient samples of difficult-to-treat infections directly on nutrient-rich agar and monitored colony growth by time-lapse imaging. We retained 36 Staphylococcus aureus monocultures for further analysis. We investigated clinical factors associated with increased colony growth-delay with regression analyses. We corroborated the clinical findings using in vitro grown static biofilms exposed to distinct antibiotics., Results: The extent of phenotypic heterogeneity of patient-derived S. aureus varied substantially between patients (from no delay to a maximum of 57.6 hours). Increased heterogeneity coincided with increased median colony growth-delay. Multivariable regression showed that rifampicin treatment was significantly associated with increased median growth-delay (13.3 hours; 95% CI 7.13-19.6 hours; p < 0.001). S. aureus grown in biofilms and exposed to high concentrations of rifampicin or a combination of rifampicin with clindamycin or levofloxacin exhibited prolonged growth-delay (p < 0.05 for 11 of 12 comparisons), correlating with a strain-dependent increase in antibiotic tolerance., Discussion: Colony-size heterogeneity upon direct sampling of difficult-to-treat S. aureus infections was frequently observed. Hence, future studies are needed to assess the potential benefit of phenotypic heterogeneity quantification for staphylococcal infection prognosis and treatment guidelines., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mental files theory explains why children pass many perspective taking tasks like the false belief test around age 4 (Perner & Leahy, 2016). It also explains why older children struggle to understand that beliefs about an object depend on how one is acquainted with it (intensionality or aspectuality). If Heinz looks at an object that is both a die and an eraser, but cannot tell by looking that it is an eraser, he will not reach for it if he needs an eraser. Four- to 6-year olds find this difficult (Apperly & Robinson, 1998). We tested 129 35- to 86-month olds with a modified version of Apperly and Robinson's task. Each child faced four tasks resulting from two experimental factors, timing and mode of information. Timing: Children saw Heinz learn the die's location either before or after they learn that the die is an eraser. Mode of information: Heinz learns where the die is either perceptually or verbally. When Heinz' learning is verbal, he never perceives the die at all. We found that Apperly and Robinson's problem occurs only in the seen-after condition, where Heinz sees the die afterchildren had learnt that it was also an eraser. It vanishes when Heinz learns where the die is before children learn that it is also an eraser. The problem also vanishes when Heinz learns where the die is purely verbally (e.g., "The die is in the red box") and never sees it. This evidence lets us refine existing mental files theory, and eliminate several alternatives from the literature., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

We provide a cognitive analysis of how children represent belief using mental files. We explain why children who pass the false belief test are not aware of the intensionality of belief. Fifty-one 3½- to 7-year old children were familiarized with a dual object, e.g., a ball that rattles and is described as a rattle. They observed how a puppet agent witnessed the ball being put into box 1. In the agent's absence the ball was taken from box 1, the child was reminded of it being a rattle, and emphasising its being a rattle it was put back into box 1. Then the agent returned, the object was hidden in the experimenter's hands and removed from box 1, described as a "rattle," and transferred to box 2. Children who passed false belief had no problem saying where the puppet would look for the ball. However, in a different condition in which the agent was also shown that the ball was a rattle they erroneously said that the agent would look for the ball in box 1, ignoring the agent's knowledge of the identity of rattle and ball. Their problems cease with their mastery of second-order beliefs (she thinks she knows). Problems also vanish when the ball is described not as a rattle but as a thing that rattles. We describe how our theory can account for these data as well as all other relevant data in the literature., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The objective of this study was to determine course and treatment of atrial fibrillation (AF) in nonagenarians. Incidence of AF increases with age. Due to the demographic change in the industrialized world, an increase of AF in the group of elderly and very elderly is expected in the next decades. However, only few data exist on the clinical relevance of AF in patients aged 89 years or older., Design: Observational, mono-centric registry., Setting: University hospital., Participants: Of the 11,888 patients included in the Berlin Atrial Fibrillation (BAF) Registry, 279 patients aged 89 years or older were identified. All patients presented to our hospital with AF between January 2001 and December 2014., Measurements: AF type, symptoms, comorbidities, CHA2DS2-VASc and HAS-BLED, treatment strategy, and anticoagulant treatment were assessed at baseline. A composite of stroke/transient ischemic attack (TIA), thromboembolic events, major bleeding, and death was the primary endpoint. Stroke/TIA, thromboembolic events and major bleeding, presence of AF, new onset of heart failure and change of NYHA class, and bradyarrhythmia necessitating pacemaker implantation were secondary endpoints., Results: Patients (age 92 ± 2.7 years, range 89-108) presented in EHRA class I in 38.4% of the cases, class II in 49.5%, class III in 10%, and class IV in 2%. Rhythm control was attempted in 37 (13.3%) of the patients. Baseline CHA2DS2-VASc and HAS-BLED were 5.0 ± 1.3 and 3.1 ± 0.9, respectively. Oral anticoagulation (OAC) was initiated in 74 (26.5 %) of the patients. Of all patients, 33 (11.8%) patients died in hospital. Of the remaining patients, 104 were followed over 13.8 ± 17.5 months with 3.5 ± 2.3 visits during follow-up. Rhythm control was attempted in 10 patients (9.6%). OAC was initiated in 37 patients (35.6 %). Fifty-nine (56.7%) patients reached the primary composite endpoint. Stroke/TIA (34.6%) and heart failure (49%) were common. Subgroup analysis revealed no significant differences in any of the endpoints between patients undergoing rhythm versus rate control and between patients under OAC compared with patients without OAC. INR at follow-up and TTR were 1.76 ± 1.0 and 29.5% ± 37.8% in patients receiving VKA., Conclusion: In this real-world cohort of very elderly patients with AF, a rhythm control strategy and OAC treatment were chosen only in a minority of the cases. If OAC was initiated, most received VKAs with a poor TTR during follow-up. A high incidence of stroke/TIA was observed in patients with and without OAC. Further data are needed to define optimal treatment of AF in this particular patient group., (Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the prognostic value of mid-regional proadrenomedullin (MR-proADM) in atrial fibrillation (AF) patients undergoing radiofrequency ablation., Methods: Plasma concentrations of MR-proADM were measured at baseline and after 12months in 87 AF patients in whom radiofrequency ablation was performed. The association between MR-proADM and AF recurrence was tested by univariable and multivariable Cox models., Results: In all 87 patients radiofrequency ablation was successfully performed. Of the total population 54% had paroxysmal AF. The mean left ventricular ejection fraction was 54% (minimum 25%). After 12months of follow-up, 71% of the patients were free of AF recurrence. At baseline, mean MR-proADM in the total population was 0.72nmol/l±0.22. Patients with AF recurrence had significantly higher baseline MR-proADM (0.89nmol/l±0.29) as compared with patients without AF recurrence (0.65nmol/l±0.14; p<0.001). After 12months, mean MR-proADM plasma concentration remained higher in patients with AF recurrence (0.81nmol/l±0.22 as compared with patients free of AF 0.54nmol/l±0.20; p<0.001). Receiver operating characteristic (ROC) curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 64% with an optimal cut-off value of 0.82nmol/l to predict recurrence of AF after catheter ablation. In the logistic regression analysis only MR-proADM remained independently predictive for AF recurrence., Conclusion: This is the first study revealing the association between MR-proADM elevation before ablation and poor outcomes after ablation of AF. Larger studies are needed to validate these results., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Catheter ablation is a curative treatment option for ventricular premature contractions (VPC) and ventricular tachycardia (VT). Procedures require different sedation levels, depending on duration, ablation approach and patient characteristics. The aim of our study was to evaluate feasibility of minimal and deep sedation for ablation of VPC/VT., Methods: Patients underwent catheter ablation of VPC/VT under minimal or deep sedation. Events of hypotension, hypoxia, bradycardia, procedural complications and VT inducibility were compared between the groups., Results: 120 patients were included. In 42 patients (53.6 ± 17.1 years, 47.6% male) ablation was performed under minimal sedation with midazolam, and in 78 patients (54.2 ± 17.5 years, 67.9% male) ablation was performed under deep sedation with propofol/midazolam. There were significantly fewer patients with idiopathic VT (62.8 vs. 88.1%, p=0.011) in the deep sedation group, LVEF was significantly lower (47 ± 14.4 vs. 53.1 ± 11.7) and the procedure duration was significantly longer (201.9 ± 85.9 vs. 137.9 ± 98.7). No significant differences in procedural complications or sedation related events (hypotension: 0 vs. 3.8%, p=0.2, no hypoxia, no bradycardia) were detected., Conclusions: Minimal sedation and deep sedation are both feasible during VPC/VT ablation procedures. Propofol does not increase complications even in a collective with pre-existing impairment of LVEF. Adequate monitoring and trained personnel should be present., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Single nucleotide polymorphisms (SNPs) of EPHX2 alter sEH activity and are associated with increased [rs41507953 (K55R)] or reduced [rs751141 (R287Q)] cardiovascular risk via modulation of fibrosis, inflammation or cardiac ion channels. This indicates an effect on development and therapy response of AF. This study tested the hypothesis that variations in the EPHX2 gene encoding human soluble epoxide hydrolase (sEH) are associated with atrial fibrillation (AF) and recurrence of atrial fibrillation after catheter ablation., Methods and Results: A total of 218 consecutive patients who underwent catheter ablation for drug refractory AF and 268 controls were included. Two SNPs, rs41507953 and rs751141, were genotyped by direct sequencing. In the ablation group, holter recordings 3, 12 and 24 months after ablation were used to detect AF recurrence. No significant association of the SNPs and AF at baseline was detected. In the ablation group, recurrence of AF occurred in 20% of the patients 12 months after ablation and in 35% 24 months after ablation. The presence of the rs751141 polymorphism significantly increased the risk of AF recurrence 12 months (odds ratio [OR]: 3.2, 95% confidence interval [CI]: 1.237 to 8.276, p=0.016) and 24 months (OR: 6.076, 95% CI: 2.244 to 16.451, p<0.0001) after catheter ablation., Conclusions: The presence of rs751141 polymorphism is associated with a significantly increased risk of AF recurrence after catheter ablation. These results point to stratification of catheter ablation by genotype and differential use of sEH-inhibitory drugs in the future., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Cardiac troponin I (cTnI) is highly specific for myocardial damage and for the diagnosis of acute coronary syndrome. We investigated cTnI utility and predictive value in patients with atrial fibrillation (AF) in the acute setting., Method: We studied 354 consecutive patients with the primary diagnosis of AF and clinical symptoms suggestive of myocardial ischemia presenting to our emergency department. cTnI was obtained on presentation. Patients with ST-segment elevation myocardial infarction were excluded. Coronary angiography was performed in 100 patients., Results: cTnI was elevated (>0.09 μg/L) in 51 of 354 (15%) patients. The mean cTnI in these patients was 0.37 μg/L (0.09-3.14). In 23 of 100 patients undergoing coronary angiography, cTnI was elevated. Only 6 of these 23 patients (26%) had significant stenosis. In 77 of 100 patients undergoing coronary angiography, cTnI was normal, revealing significant stenosis in 25 patients (33%). The positive predictive value of elevated cTnI for a coronary intervention was 26% and the negative predictive value was 68%. Using multivariate logistic regression, we found that heart rate on presentation, the presence of angina pectoris, left ventricular ejection fraction, serum creatinine, and hemoglobin independently predicted elevated cTnI level., Conclusion: These data are the first to show that AF in the acute setting is frequently associated with cTnI elevations. AF patients with high heart rate and/or angina pectoris often show false elevated cTnI levels. These findings are relevant for clinicians evaluating patients with acute AF and myocardial ischemia symptoms. Appropriate clinical guidelines must be established that also consider AF-related elevations in cTnI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)