Measuring Expressive Music Performances: a Performance Science Model using Symbolic Approximation

Music Performance Science (MPS), sometimes termed systematic musicology in Northern Europe, is concerned with designing, testing and applying quantitative measurements to music performances. It has applications in art musics, jazz and other genres. It is least concerned with aesthetic judgements or with ontological considerations of artworks that stand alone from their instantiations in performances. Musicians deliver expressive performances by manipulating multiple, simultaneous variables including, but not limited to: tempo, acceleration and deceleration, dynamics, rates of change of dynamic levels, intonation and articulation. There are significant complexities when handling multivariate music datasets of significant scale. A critical issue in analyzing any types of large datasets is the likelihood of detecting meaningless relationships the more dimensions are included. One possible choice is to create algorithms that address both volume and complexity. Another, and the approach chosen here, is to apply techniques that reduce both the dimensionality and numerosity of the music datasets while assuring the statistical significance of results. This dissertation describes a flexible computational model, based on symbolic approximation of timeseries, that can extract time-related characteristics of music performances to generate performance fingerprints (dissimilarities from an ‘average performance’) to be used for comparative purposes. The model is applied to recordings of Arnold Schoenberg’s Phantasy for Violin with Piano Accompaniment, Opus 47 (1949), having initially been validated on Chopin Mazurkas.1 The results are subsequently used to test hypotheses about evolution in performance styles of the Phantasy since its composition. It is hoped that further research will examine other works and types of music in order to improve this model and make it useful to other music researchers. In addition to its benefits for performance analysis, it is suggested that the model has clear applications at least in music fraud detection, Music Information Retrieval (MIR) and in pedagogical applications for music education

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Novel thioglycoside analogs of ?-galactosylceramide stimulate cytotoxicity and preferential Th1 cytokine production by human invariant natural killer T cells

Invariant natural killer T (iNKT) cells recognize glycolipid antigens bound to CD1d molecules on antigen-presenting cells. Therapeutic activation of iNKT cells with the xenogeneic glycolipid ?-galactosylceramide (?-GalCer) can prevent and reverse tumor growth in murine models, but clinical trials using ?-GalCer-stimulated human iNKT cells have shown limited efficacy. We synthesized a series of thioglycoside analogs of ?-GalCer with different substituents to the galactose residue and found that two of these compounds, XZ7 and XZ11, bound to CD1d-transfected HeLa cells and activated lines of expanded human iNKT cells. Both compounds stimulated cytolytic degranulation by iNKT cells and while XZ7 preferentially stimulated the production of the antitumor cytokine interferon-? (IFN-?), XZ11 preferentially stimulated interleukin-4 (IL-4) production. This biased T helper type 1 effector profile of XZ7 was also evident when iNKT were stimulated with dendritic cells presenting this glycolipid. Separate analysis of the responses of CD4+, CD8?+ and CD4?CD8? iNKT cells indicated that XZ7 preferentially activated CD8?+ iNKT cells, and to a lesser degree, CD4?CD8? iNKT cells. The partial agonist effect of glycolipid XZ7, inducing cytotoxicity and IFN-? production but not IL-4 production, indicates that specific protumour activities of iNKT cells can be abolished, while preserving their antitumor activities, by introducing structural modifications to ?-GalCer. Since XZ7 was much less potent than ?-GalCer as an iNKT cell agonist, it is unlikely to be superior to ?-GalCer as a therapeutic agent for cancer, but may serve as a parent compound for developing more potent structural analogs