Atonal Music: Can Uncertainty Lead to Pleasure?

In recent years, the field of neuroaesthetics has gained considerable attention with music being a favored object of study. The majority of studies concerning music have, however, focused on the experience of Western tonal music (TM), which is characterized by tonal hierarchical organization, a high degree of consonance, and a tendency to provide the listener with a tonic as a reference point during the listening experience. We argue that a narrow focus on Western TM may have led to a one-sided view regarding the qualities of the aesthetic experience of music since Western art music from the 20th and 21st century like atonal music (AM) – while lacking a tonal hierarchical structure, and while being highly dissonant and hard to predict – is nevertheless enjoyed by a group of avid listeners. We propose a research focus that investigates, in particular, the experience of AM as a novel and compelling way with which to enhance our understanding of both the aesthetic appreciation of music and the role of predictive models in the context of musical pleasure. We use music theoretical analysis and music information retrieval methods to demonstrate how AM presents the listener with a highly uncertain auditory environment. Specifically, an analysis of a corpus of 100 musical segments is used to illustrate how tonal classical music and AM differ quantitatively in terms of both key and pulse clarity values. We then examine person related, extrinsic and intrinsic factors, that point to potential mechanisms underlying the appreciation and pleasure derived from AM. We argue that personality traits like “openness to experience,” the framing of AM as art, and the mere exposure effect are key components of such mechanisms. We further argue that neural correlates of uncertainty estimation could represent a central mechanism for engaging with AM and that such contexts engender a comparatively weak predictive model in the listener. Finally we argue that in such uncertain contexts, correct predictions may be more subjectively rewarding than prediction errors since they signal to the individual that their predictive model is improving

Quantitative High-Resolution Genomic Analysis of Single Cancer Cells

During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

The adaptive significance of chromatophores in the Arctic under-ice amphipod Apherusa glacialis

Solar radiation is a crucial factor governing biological processes in polar habitats. Containing harmful ultraviolet radiation (UVR), it can pose a threat for organisms inhabiting surface waters of polar oceans. The present study investigated the physiological color change in the obligate sympagic amphipod Apherusa glacialis mediated by red-brown chromatophores, which cover the body and internal organs of the species. Short-term experimental exposure to photosynthetic active radiation (PAR) led to pigment dispersal in the chromatophores, resulting in darkening of the animal. Irradiation in the PAR range (400-700 nm) was identified as the main trigger with high light intensities evoking marked responses within 15 min. After exposure to high PAR, darkness led to a slow aggregation of pigments in the cell center after 24 h. Experiments revealed no statistically significant change in coloration of the animal when exposed to different background colors nor UV radiation. Our results point to a dose- and time-dependent photoprotective role of chromatophores in the amphipod, presuming a shielding effect from harmful radiation in a dispersed state. The reversible nature of the physiological color change enables the species to adapt dynamically to prevailing light conditions and thereby minimize the cost of increased conspicuousness toward visually hunting predators

Identifying characteristics of adolescents with persistent loneliness during COVID‐19: A multi‐country eight‐wave longitudinal study

BackgroundElevated loneliness experiences characterise young people. While loneliness at this developmental juncture may emerge from age-typical upheaval in social relationships, there is little data on the extent to which young people experience high and persistent levels of loneliness, and importantly, who is most vulnerable to these experiences. Using the widespread social restrictions associated with the COVID-19 pandemic, which precipitated loneliness in many, we aimed to examine adolescents' loneliness profiles across time and the demographic predictors (age, sex, and country) of more severe trajectories.MethodsParticipants aged 12–18 years, recruited into a multi-wave study (N = 1039) across three sites (UK, Israel, and India) completed a 3-item loneliness measure fortnightly across 8 timepoints during the pandemic.ResultsLatent class growth analysis suggested 5 distinct trajectories: (1) low stable (33%), (2) low increasing (19%), (3) moderate decreasing (17%), (4) moderate stable (23%), and (5) high increasing (8%). Females and older adolescents were more likely to experience persistently high loneliness.ConclusionsThese findings indicate a need for interventions to reduce loneliness in adolescents as we emerge from the pandemic, particularly for those groups identified as being at highest risk.<br/

Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging

Protein persulfidation is a significant post-translational modification that involves addition of a sulfur atom to the cysteine thiol group and is facilitated by sulfide species. Persulfidation targets reactive cysteine residues within proteins, influencing their structure and/or function across various biological systems. This modification is evolutionarily conserved and plays a crucial role in preventing irreversible cysteine overoxidation, a process that becomes prominent with aging. While, persulfidation decreases with age, its levels in the aged heart and the functional implications of such a reduction in cardiac metabolism remain unknown. Here we interrogated the cardiac persulfydome in wild-type adult mice and age-matched mice lacking the two sulfide generating enzymes, namely cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). Our findings revealed that cardiac persulfidated proteins in wild type hearts are less abundant compared to those in other organs, with a primary involvement in mitochondrial metabolic processes. We further focused on one specific target, NDUFB7, which undergoes persulfidation by both CSE and 3MST derived sulfide species. In particular, persulfidation of cysteines C80 and C90 in NDUFB7 protects the protein from overoxidation and maintains the complex I activity in cardiomyocytes. As the heart ages, the levels of CSE and 3MST in cardiomyocytes decline, leading to reduced NDUFB7 persulfidation and increased cardiac NADH/NAD+ ratio. Collectively, our data provide compelling evidence for a direct link between cardiac persulfidation and mitochondrial complex I activity, which is compromised in aging

Cluster Randomized Controlled Trial on the Effects of 12 Months of Combined Exercise Training during Hemodialysis in Patients with Chronic Kidney Disease-Study Protocol of the Dialysis Training Therapy (DiaTT) Trial

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months' intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology

Pregnancy outcomes in women with rheumatic mitral valve disease: Results from the registry of pregnancy and cardiac disease

BACKGROUND: Cardiac disease is 1 of the major causes of maternal mortality. We studied pregnancy outcomes in women with rheumatic mitral valve disease. METHODS: The Registry of Pregnancy and Cardiac Disease is an international prospective registry, and consecutive pregnant women with cardiac disease were included. Pregnancy outcomes in all women with rheumatic mitral valve disease and no prepregnancy valve replacement is described in the present study (n=390). A maternal cardiac event was defined as cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, and hospitalization for other cardiac reasons or cardiac intervention. Associations between patient characteristics and cardiac outcomes were checked in a 3-level model (patient-center-country). RESULTS: Most patients came from emerging countries (75%). Mitral stenosis (MS) with or without mitral regurgitation (MR) was present in 273 women, isolated MR in 117. The degree of MS was mild in 20.9%, moderate in 39.2%, severe in 19.8%, and severity not classified in the remainder. Maternal death during pregnancy occurred in 1 patient with severe MS. Hospital admission occurred in 23.1% of the women with MS, and the main reason was heart failure (mild MS 15.8%, moderate 23.4%, severe 48.1%; PCONCLUSIONS: Although mortality was only 1.9% during pregnancy, ∼50% of the patients with severe rheumatic MS and 23% of those with significant MR developed heart failure during pregnancy. Prepregnancy counseling and considering mitral valve interventions in selected patients are important to prevent these complications.</p

Pulmonary hypertension and pregnancy outcomes: Data from the Registry of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology

Aims: To describe the outcomes of pregnancy in women with pulmonary hypertension. Methods and results: In 2007 the European Registry on Pregnancy and Heart Disease was initiated by the European Society of Cardiology. Consecutive patients with all forms of cardiovascular disease, presenting with pregnancy, were enrolled with the aim of investigating the pregnancy outcomes. This subgroup of the cohort included 151 women with pulmonary hypertension (PH) either diagnosed by right heart catheterization or diagnosed as possible PH by echocardiographic signs, with 26% having pulmonary arterial hypertension (PAH), in three subgroups: idiopathic (iPAH), associated with congenital heart disease (CHD-PAH), or associated with other disease (oPAH), and 74% having PH caused by left heart disease (LHD-PH, n = 112). Maternal mean age was 29.2 ± 5.6 years and 37% were nulliparous. Right ventricular systolic pressure was 70 mmHg in 11.9%. In more than 75% of patients, the diagnosis of PH had been made before pregnancy. Maternal death up to 1 week after delivery occurred in five patients (3.3%), with another two out of 78 patients who presented for follow-up (2.6%), dying within 6 months after delivery. The highest mortality was found in iPAH (3/7, 43%). During pregnancy, heart failure occurred in 27%. Caesarean section was performed in 63.4% (23.9% as emergency). Therapeutic abortion was performed in 4.0%. Complications included miscarriage (5.6%), fetal mortality (2%), premature delivery (21.7%), low birth weight (19.0%), and neonatal mortality (0.7%). Conclusion: Mortality in this group of patients with various forms of PH was lower than previously reported as specialized care during pregnancy and delivery was available. However, maternal and fetal mortality remains prohibitively high in women with iPAH, although this conclusion is restricted by limited numbers. Early advice on contraception, pregnancy risk and fetal outcome remains paramount.</p

Pregnancy in women with a mechanical heart valve: Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC)

Background - Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results - Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (P=1.000), and in 0.2% of patients without a prosthetic valve (P=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (P<0.001), and in 4.9% of patients without a prosthetic valve (P<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (P<0.001) and 78% of patients without a prosthetic valve (P<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P<0.001) and late fetal death (7.1% versus 0.7%; P=0.016). Conclusions - Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.</p