Emotional Processing in Music: Study in Affective Responses to Tonal Modulation in Controlled Harmonic Progressions and Real Music

Tonal modulation is one of the main structural and expressive aspects of music in the European musical tradition. Experiment 1 investigated affective responses to modulations to all eleven major and minor keys (relative to the starting tonality) in brief, specially constructed harmonic progressions, by using six bipolar scales related to valence, potency, and synaesthesia. The results indicated the dependence of affective response on degree of modulation in terms of key proximity, and of mode. Experiment 2 examined affective responses to the most common modulations in nineteenth-century piano music: to the subdominant, dominant, and minor sixth in the major mode. The stimuli were a balanced set of both harmonic progressions (as in Experiment 1) and real music excerpts. The results agreed with theoretical models of violations of expectancy and of proximity based on the circle of fifths, and demonstrated the influence of melodic direction and musical style on emotional response to tonal modulation

Memory and the Experience of Hearing Music

We report five experiments in which listeners heard the beginnings of classical minuets (or similar dances). The phrase in either measures 1-2 or measures 3-4 was selected as a target, tested at the end of the excerpt. A beep indicated the test item, which was a continuation of the minuet as written. Test items were targets (repetitions of the selected phrase), similar lures (imitations of targets), or different lures, and occurred after delays of 4-5, 15, or 30 s. We estimated the proportion of correct discriminations of targets from similar lures and targets from different lures. In Experiment 1, discrimination of targets from similar lures (but not of targets from different lures) improved between 5 and 15 s. Experiment 2 extended this result to a delay of 30 s. Discrimination of targets from similar lures improved over time, especially for second-phrase targets. This improvement was due mainly to decreasing false alarms to similar lures. Experiments 3 and 4 replaced the continuous music with silence and with a repetitive oom-pah-pah pattern, and the improvement in discrimination of targets from similar lures disappeared. Experiment 5 removed listeners\u27 expectations of being tested, and the improvement also disappeared. Results are considered in the framework of current theories of memory, and their implications for the listener\u27s experience of hearing music are discussed

Recognition of Familiar and Unfamiliar Melodies in Normal Aging and Alzheimers-Disease

We tested normal young and elderly adults and elderly Alzheimer\u27s disease (AD) patients on recognition memory for tunes. In Experiment 1, AD patients and age-matched controls received a study list and an old/new recognition test of highly familiar, traditional tunes, followed by a study list and test of novel tunes. The controls performed better than did the AD patients. The controls showed the \u27\u27mirror effect\u27\u27 of increased hits and reduced false alarms for traditional versus novel tunes, whereas the patients false-alarmed as often to traditional tunes as to novel tunes. Experiment 2 compared young adults and healthy elderly persons using a similar design. Performance was lower in the elderly group, but both younger and older subjects showed the mirror effect. Experiment 3 produced confusion between preexperimental familiarity and intraexperimental familiarity by mixing traditional and novel tunes in the study lists and tests. Here, the subjects in both age groups resembled the patients of Experiment 1 in failing to show the mirror effect. Older subjects again performed more poorly, and they differed qualitatively from younger subjects in setting stricter criteria for more nameable tunes. Distinguishing different sources of global familiarity is a factor in tune recognition, and the data suggest that this type of source monitoring is impaired in AD and involves different strategies in younger and older adults

Perception of Mode, Rhythm, and Contour in Unfamiliar Melodies: Effects of Age and Experience

We explored the ability of older (60-80 years old) and younger (18-23 years old) musicians and nonmusicians to judge the similarity of transposed melodies varying on rhythm, mode, and/or contour (Experiment 1) and to discriminate among melodies differing only in rhythm, mode, or contour (Experiment 2). Similarity ratings did not vary greatly among groups, with tunes differing only by mode being rated as most similar. In the same/different discrimination task, musicians performed better than nonmusicians, but we found no age differences. We also found that discrimination of major from minor tunes was difficult for everyone, even for musicians. Mode is apparently a subtle dimension in music, despite its deliberate use in composition and despite people\u27s ability to label minor as sad and major as happy

Altered Metabolism and Persistent Starvation Behaviors Caused by Reduced AMPK Function in Drosophila

Organisms must utilize multiple mechanisms to maintain energetic homeostasis in the face of limited nutrient availability. One mechanism involves activation of the heterotrimeric AMP-activated protein kinase (AMPK), a cell-autonomous sensor to energetic changes regulated by ATP to AMP ratios. We examined the phenotypic consequences of reduced AMPK function, both through RNAi knockdown of the gamma subunit (AMPKγ) and through expression of a dominant negative alpha (AMPKα) variant in Drosophila melanogaster. Reduced AMPK signaling leads to hypersensitivity to starvation conditions as measured by lifespan and locomotor activity. Locomotor levels in flies with reduced AMPK function were lower during unstressed conditions, but starvation-induced hyperactivity, an adaptive response to encourage foraging, was significantly higher than in wild type. Unexpectedly, total dietary intake was greater in animals with reduced AMPK function yet total triglyceride levels were lower. AMPK mutant animals displayed starvation-like lipid accumulation patterns in metabolically key liver-like cells, oenocytes, even under fed conditions, consistent with a persistent starved state. Measurements of O2 consumption reveal that metabolic rates are greater in animals with reduced AMPK function. Lastly, rapamycin treatment tempers the starvation sensitivity and lethality associated with reduced AMPK function. Collectively, these results are consistent with models that AMPK shifts energy usage away from expenditures into a conservation mode during nutrient-limited conditions at a cellular level. The highly conserved AMPK subunits throughout the Metazoa, suggest such findings may provide significant insight for pharmaceutical strategies to manipulate AMPK function in humans

Spontaneous singing and musical agency in the everyday home lives of three- and four-year-old children

Spontaneous singing permeates the lives of young children and can provide insights into the social and personal worlds of young children at home. Research into young children’s singing has traditionally been dominated by studies framed by developmental perspectives. However, developmental approaches run the risk of overlooking the ways in which spontaneous singing is useful and meaningful to young children. Despite increased interest in the musical lives of young children, there exists very little research into young children’s musical lives at home, largely because the home can be a difficult space to access for research purposes. This chapter is based on research undertaken from audio recordings of 15 3- and 4-year-old children who were recorded for continuous periods at home using all-day recording technology. I draw on ideas from music sociology and childhood studies to illustrate how children use singing as a tool of agency in their interactions with others and to manage their own experience

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics. Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study—a multi-site sample of 9–10 year-olds (n = 11,875)—and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels. Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child\u27s weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample. Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer