The Rise of the Sentient Musical Instrument: A Study of Hieronymus Bosch\u27s Musical Instruments and their Dissonant Revolution

This essay examines the evolution of Hieronymus Bosch\u27s musical instruments from silent props to sentient characters. It follows the course of the instruments\u27 progression, beginning with the influence of preceding artists and Bosch\u27s early work, and ends with the climactic Hell panel of the Garden of Earthly Delights in which the instruments have gained complete independence and dominate the human souls. The theories of Aristotle, Tinctoris, Machaut, Dante and the Devotio Moderna are analyzed for their highly influential effects on the instruments\u27 liberation, particularly concerning their belief in the musical body and soul

Extreme morning chronotypes are often familial and not exceedingly rare: the estimated prevalence of advanced sleep phase, familial advanced sleep phase, and advanced sleep-wake phase disorder in a sleep clinic population.

Study objectivesReport the first prevalence estimates of advanced sleep phase (ASP), familial advanced sleep phase (FASP), and advanced sleep-wake phase disorder (ASWPD). This can guide clinicians on the utility of screening for extreme chronotypes both for clinical decision-making and to flag prospective participants in the study of the genetics and biology of FASP.MethodsData on morning or evening sleep schedule preference (chronotype) were collected from 2422 new patients presenting to a North American sleep center over 9.8 years. FASP was determined using a severity criterion that has previously identified dominant circadian mutations in humans. All patients were personally seen and evaluated by one of the authors (C.R.J.).ResultsOur results demonstrate an ASP prevalence of 0.33%, an FASP prevalence of 0.21%, and an ASWPD prevalence of at least 0.04%. Most cases of young-onset ASP were familial.ConclusionsAmong patients presenting to a sleep clinic, conservatively 1 out of every 300 patients will have ASP, 1 out of every 475 will have FASP, and 1 out of every 2500 will have ASWPD. This supports obtaining a routine circadian history and, for those with extreme chronotypes, obtaining a family history of circadian preference. This can optimize treatment for evening sleepiness and early morning awakening and lead to additional circadian gene discovery. We hope these findings will lead to improved treatment options for a wide range of sleep and medical disorders in the future

Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder

ABSTRACTObjective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P&lt;.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P&lt;.0001).Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.</jats:p

No Place for Predators?: Time and again, advancing civilization has set people against large carnivores. On the front lines of Washington State, wildlife biologists hope that knowledge can trump fear, and ultimately lead to détente.

When voters in Washington State banned hound hunting with an eye to protecting cougars, they unwittingly triggered a chain of events that wildlife biologists are still trying to understand

High spatial resolution mass spectrometry imaging reveals the genetically programmed, developmental modification of the distribution of thylakoid membrane lipids among individual cells of maize leaf

Metabolism in plants is compartmentalized among different tissues, cells and subcellular organelles. Mass spectrometry imaging (MSI) with matrix-assisted laser desorption ionization (MALDI) has recently advanced to allow for the visualization of metabolites at single cell resolution. Here we applied 5 and 10 m high-spatial resolution MALDI-MSI to the asymmetric Kranz anatomy of maize leaves to study the differential localization of two major anionic lipids in thylakoid membranes, sulfoquinovosyldiacylglycerols (SQDG) and phosphatidylglycerols (PG). The quantification and localization of SQDG and PG molecular species, among mesophyll (M) and bundle sheath (BS) cells, are compared across the leaf developmental gradient from four maize genotypes (the inbreds B73 and Mo17, and reciprocal hybrids B73xMo17 and Mo17xB73). SQDG species are uniformly distributed in both photosynthetic cell types regardless of leaf development or genotype. However, PG shows photosynthetic cell-specific differential localization depending on the genotype and the fatty acyl chain constituent. Overall, 16:1-containing PGs primarily contribute to the thylakoid membranes of M cells while BS chloroplasts are mostly composed of 16:0-containing PGs. Furthermore, PG 32:0 shows genotype-specific differences in cellular distribution, with preferential localization in BS cells for B73, but more uniform distribution between BS and M cells in Mo17. Maternal inheritance is exhibited within the hybrids such that localization of PG 32:0 in B73xMo17 is similar to the distribution in the B73 parental inbred, whereas that of Mo17xB73 resembles the Mo17 parent. This study demonstrates the power of MALDI-MSI to reveal unprecedented insights on metabolic outcomes in multicellular organisms at single cell resolution

Spatial Mapping and Profiling of Metabolite Distributions During Germination

Germination is a highly complex process by which seeds begin to develop and establish themselves as viable organisms. In this paper, we utilize a combination of GC-MS, LC-fluorescence, and mass spectrometry imaging (MSI) approaches to profile and visualize the metabolic distributions of germinating seeds from two different inbreds of maize seeds, B73 and Mo17. GC and LC analyses demonstrate that the two inbreds are highly differentiated in their metabolite profiles throughout the course of germination, especially with regard to amino acids, sugar alcohols, and small organic acids. Crude dissection of the seed followed by GC-MS analysis of polar metabolites also revealed that many compounds were highly sequestered among the various seed tissue types. To further localize compounds, matrix-assisted laser desorption/ionization MSI is utilized to visualize compounds in fine detail in their native environments over the course of germination. Most notably, the fatty acyl chain-dependent differential localization of phospholipids and TAGs were observed within the embryo and radicle, showing correlation with the heterogeneous distribution of fatty acids. Other interesting observations include unusual localization of ceramides on the endosperm/scutellum boundary, and subcellular localization of ferulate in the aleurone

Consequences of Internet Use in College Students

The purposes of the research project were to explore how much time college students spend on the Internet and the consequences for college students who use the Internet

Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n&nbsp;=&nbsp;1986), primarily using no substances; licit use (6.6%; n&nbsp;=&nbsp;145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n&nbsp;=&nbsp;64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P&nbsp;=&nbsp;.001, d&nbsp;=&nbsp;.64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P&nbsp;&lt;&nbsp;.001, d&nbsp;=&nbsp;.16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles