Language of music: a computational model of music interpretation

Automatic music transcription (AMT) is commonly defined as the process of converting an acoustic musical signal into some form of musical notation, and can be split into two separate phases: (1) multi-pitch detection, the conversion of an audio signal into a time-frequency representation similar to a MIDI file; and (2) converting from this time-frequency representation into a musical score. A substantial amount of AMT research in recent years has concentrated on multi-pitch detection, and yet, in the case of the transcription of polyphonic music, there has been little progress. There are many potential reasons for this slow progress, but this thesis concentrates on the (lack of) use of music language models during the transcription process. In particular, a music language model would impart to a transcription system the background knowledge of music theory upon which a human transcriber relies. In the related field of automatic speech recognition, it has been shown that the use of a language model drawn from the field of natural language processing (NLP) is an essential component of a system for transcribing spoken word into text, and there is no reason to believe that music should be any different. This thesis will show that a music language model inspired by NLP techniques can be used successfully for transcription. In fact, this thesis will create the blueprint for such a music language model. We begin with a brief overview of existing multi-pitch detection systems, in particular noting four key properties which any music language model should have to be useful for integration into a joint system for AMT: it should (1) be probabilistic, (2) not use any data a priori, (3) be able to run on live performance data, and (4) be incremental. We then investigate voice separation, creating a model which achieves state-of-the-art performance on the task, and show that, used as a simple music language model, it improves multi-pitch detection performance significantly. This is followed by an investigation of metrical detection and alignment, where we introduce a grammar crafted for the task which, combined with a beat-tracking model, achieves state-of-the-art results on metrical alignment. This system’s success adds more evidence to the long-existing hypothesis that music and language consist of extremely similar structures. We end by investigating the joint analysis of music, in particular showing that a combination of our two models running jointly outperforms each running independently. We also introduce a new joint, automatic, quantitative metric for the complete transcription of an audio recording into an annotated musical score, something which the field currently lacks

Starting, building and sustaining a program of research in emergency medicine in Canada

Objective: To develop pragmatic recommendations for starting, building and sustaining a program of research in emergency medicine (EM) in Canada at sites with limited infrastructure and/or prior research experience. Methods: At the direction of the Canadian Association of Emergency Physicians (CAEP) academic section, we assembled an expert panel of 10 EM researchers with experience building programs of research. Using a modified Delphi approach, our panel developed initial recommendations for (1) starting, (2) building, and (3) sustaining a program of research in EM. These recommendations were peer-reviewed by emergency physicians and researchers from each of the panelist’s home institutions and tested for face and construct validity, as well as ease of comprehension. The recommendations were then iteratively revised based on feedback and suggestions from peer review and amended again after being presented at the 2020 CAEP academic symposium. Results: Our panel created 15 pragmatic recommendations for those intending to start (formal research training, find mentors, local support, develop a niche, start small), build (funding, build a team, collaborate, publish, expect failure) and sustain (become a mentor, obtain leadership roles, lead national studies, gain influence, prioritize wellness) a program of EM research in centers without an established research culture. Additionally, we suggest four recommendations for department leads aiming to foster a program of research within their departments. Conclusion: These recommendations serve as guidance for centres wanting to establish a program of research in EM

Automatic Note-Level Score-to-Performance Alignments in the ASAP Dataset

Several MIR applications require fine-grained note alignments between MIDI performances and their musical scores for training and evaluation. However, large and high-quality datasets with this kind of data are not available, and their manual creation is a very time-consuming task that can only be performed by field experts. In this paper, we evaluate state-of-the-art automatic note alignment models applied to dataset generation. We increase the accuracy and reliability of the produced alignments with models that flexibly leverage existing annotations such as beat or measure alignments. We thoroughly evaluate these segment-constrained models and use the best to create note alignments for the ASAP dataset, a large dataset of solo piano MIDI performances beat-aligned to MusicXML scores. The resulting note alignments are manually checked and publicly available at: https://github.com/CPJKU/asap-dataset. The contributions of this paper are four-fold: (1) we extend the ASAP dataset with reliable note alignments, thus creating (n)ASAP, the largest available fully note-aligned dataset, comprising more than 7 M annotated notes and close to 100 hours of music; (2) we design, evaluate, and publish segment-constrained models for note alignments that flexibly leverage existing annotations and significantly outperform automatic models; (3) we design, evaluate, and publish unconstrained automatic models for note alignment that produce results on par with the state of the art; (4) we introduce Parangonada, a web-interface for visualizing and correcting alignment annotations

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

Bioassay studies support the potential for latrogenic transmission of variant Creutzfeldt Jakob disease through dental procedures

Background: Evidence is required to quantify the potential risks of transmission of variant Creutzfeldt Jakob (vCJD) through dental procedures. Studies, using animal models relevant to vCJD, were performed to address two questions. Firstly, whether oral tissues could become infectious following dietary exposure to BSE? Secondly, would a vCJD-contaminated dental instrument be able to transmit disease to another patient? Methods: BSE-301V was used as a clinically relevant model for vCJD. VM-mice were challenged by injection of infected brain homogenate into the small intestine (Q1) or by five minute contact between a deliberately-contaminated dental file and the gingival margin (Q2). Ten tissues were collected from groups of challenged mice at three or four weekly intervals, respectively. Each tissue was pooled, homogenised and bioassayed in indicator mice. Findings: Challenge via the small intestine gave a transmission rate of 100% (mean incubation 157±17 days). Infectivity was found in both dental pulp and the gingival margin within 3 weeks of challenge and was observed in all tissues tested within the oral cavity before the appearance of clinical symptoms. Following exposure to deliberately contaminated dental files, 97% of mice developed clinical disease (mean incubation 234±33 days). Interpretation: Infectivity was higher than expected, in a wider range of oral tissues, than was allowed for in previous risk assessments. Disease was transmitted following transient exposure of the gingiva to a contaminated dental file. These observations provide evidence that dental procedures could be a route of cross-infection for vCJD and support the enforcement of single-use for certain dental instruments

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Bridging evidence-practice gaps: improving use of medicines in elderly Australian veterans

BACKGROUND The Australian Government Department of Veterans’ Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program. METHODS The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention. RESULTS 12 interventions were included; three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted. CONCLUSIONS The Veterans’ MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings.Elizabeth E Roughead, Lisa M Kalisch Ellett, Emmae N Ramsay, Nicole L Pratt, John D Barratt, Vanessa T LeBlanc, Philip Ryan, Robert Peck, Graeme Killer and Andrew L Gilber

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe