Bayesian methods in music modelling

This thesis presents several hierarchical generative Bayesian models of musical signals designed to improve the accuracy of existing multiple pitch detection systems and other musical signal processing applications whilst remaining feasible for real-time computation. At the lowest level the signal is modelled as a set of overlapping sinusoidal basis functions. The parameters of these basis functions are built into a prior framework based on principles known from musical theory and the physics of musical instruments. The model of a musical note optionally includes phenomena such as frequency and amplitude modulations, damping, volume, timbre and inharmonicity. The occurrence of note onsets in a performance of a piece of music is controlled by an underlying tempo process and the alignment of the timings to the underlying score of the music. A variety of applications are presented for these models under differing inference constraints. Where full Bayesian inference is possible, reversible-jump Markov Chain Monte Carlo is employed to estimate the number of notes and partial frequency components in each frame of music. We also use approximate techniques such as model selection criteria and variational Bayes methods for inference in situations where computation time is limited or the amount of data to be processed is large. For the higher level score parameters, greedy search and conditional modes algorithms are found to be sufficiently accurate. We emphasize the links between the models and inference algorithms developed in this thesis with that in existing and parallel work, and demonstrate the effects of making modifications to these models both theoretically and by means of experimental results

Sprint cycling rate of torque development associates with strength measurement in trained cyclists

Purpose: A cyclist’s rate of force/torque development (RFD/RTD) and peak force/torque can be measured during single-joint or whole-body isometric tests, or during cycling. However, there is limited understanding of the relationship between these measures, and of the mechanisms that contribute to each measure. Therefore, we examined the: (i) relationship between quadriceps central and peripheral neuromuscular function with RFD/RTD in isometric knee extension, isometric mid-thigh pull (IMTP), and sprint cycling; and (ii) relationship among RFD/RTD and peak force/torque between protocols. Methods: Eighteen trained cyclists completed two familiarisation and two experimental sessions. Each session involved an isometric knee extension, IMTP, and sprint cycling protocol, where peak force/torque, average and peak RFD/RTD, and early (0 – 100 ms) and late (0–200 ms) RFD/RTD were measured. Additionally, measures of quadriceps central and peripheral neuromuscular function were assessed during the knee extension. Results: Strong relationships were observed between quadriceps early EMG activity (EMG50/M) and knee extension RTD (r or ρ = 0.51 – 0.65) and IMTP late RFD (r = 0.51), and between cycling early or late RTD and peak twitch torque (r or ρ = 0.70 – 0.75). Strong-to-very strong relationships were observed between knee extension, IMTP, and sprint cycling for peak force/torque, early and late RFD/RTD, and peak RFD/RTD (r or ρ = 0.59 – 0.80). Conclusion: In trained cyclists, knee extension RTD or IMTP late RFD are related to measures of quadriceps central neuromuscular function, while cycling RTD is related to measures of quadriceps peripheral neuromuscular function. Further, the strong associations among force/torque measures between tasks indicate a level of transferability across tasks

A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings

Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation).In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented.We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes

Crowdsourcing HIV Test Promotion Videos: A Noninferiority Randomized Controlled Trial in China.

BACKGROUND: Crowdsourcing, the process of shifting individual tasks to a large group, may enhance human immunodeficiency virus (HIV) testing interventions. We conducted a noninferiority, randomized controlled trial to compare first-time HIV testing rates among men who have sex with men (MSM) and transgender individuals who received a crowdsourced or a health marketing HIV test promotion video. METHODS: Seven hundred twenty-one MSM and transgender participants (≥16 years old, never before tested for HIV) were recruited through 3 Chinese MSM Web portals and randomly assigned to 1 of 2 videos. The crowdsourced video was developed using an open contest and formal transparent judging while the evidence-based health marketing video was designed by experts. Study objectives were to measure HIV test uptake within 3 weeks of watching either HIV test promotion video and cost per new HIV test and diagnosis. RESULTS: Overall, 624 of 721 (87%) participants from 31 provinces in 217 Chinese cities completed the study. HIV test uptake was similar between the crowdsourced arm (37% [114/307]) and the health marketing arm (35% [111/317]). The estimated difference between the interventions was 2.1% (95% confidence interval, -5.4% to 9.7%). Among those tested, 31% (69/225) reported a new HIV diagnosis. The crowdsourced intervention cost substantially less than the health marketing intervention per first-time HIV test (US$131 vs US$238 per person) and per new HIV diagnosis (US$415 vs US$799 per person). CONCLUSIONS: Our nationwide study demonstrates that crowdsourcing may be an effective tool for improving HIV testing messaging campaigns and could increase community engagement in health campaigns. CLINICAL TRIALS REGISTRATION: NCT02248558

Therapy Insight: Parenteral Estrogen treatment for Prostate Cancer—a new dawn for an old therapy

Oral estrogens were the treatment of choice for carcinoma of the prostate for over four decades, but were abandoned because of an excess of cardiovascular and thromboembolic toxicity. It is now recognized that most of this toxicity is related to the first pass portal circulation, which upregulates the hepatic metabolism of hormones, lipids and coagulation proteins. Most of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration, which avoids hepatic enzyme induction. It also seems that a short-term but modest increase in cardiovascular morbidity (but not mortality) is compensated for by a long-term cardioprotective benefit, which accrues progressively as vascular remodeling develops over time. Parenteral estrogen therapy has the advantage of giving protection against the effects of andropause (similar to the female menopause), which are induced by conventional androgen suppression and include osteoporotic fracture, hot flashes, asthenia and cognitive dysfunction. In addition, parenteral estrogen therapy is significantly cheaper than contemporary endocrine therapy, with substantive economic implications for health providers

An overview of the clinical use of filter paper in the diagnosis of tropical diseases.

Tropical infectious diseases diagnosis and surveillance are often hampered by difficulties of sample collection and transportation. Filter paper potentially provides a useful medium to help overcome such problems. We reviewed the literature on the use of filter paper, focusing on the evaluation of nucleic acid and serological assays for diagnosis of infectious diseases using dried blood spots (DBS) compared with recognized gold standards. We reviewed 296 eligible studies and included 101 studies evaluating DBS and 192 studies on other aspects of filter paper use. We also discuss the use of filter paper with other body fluids and for tropical veterinary medicine. In general, DBS perform with sensitivities and specificities similar or only slightly inferior to gold standard sample types. However, important problems were revealed with the uncritical use of DBS, inappropriate statistical analysis, and lack of standardized methodology. DBS have great potential to empower healthcare workers by making laboratory-based diagnostic tests more readily accessible, but additional and more rigorous research is needed

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

Translational Stroke Research Using a Rabbit Embolic Stroke Model: A Correlative Analysis Hypothesis for Novel Therapy Development

Alteplase (tissue plasminogen activator, tPA) is currently the only FDA-approved treatment that can be given to acute ischemic stroke (AIS) patients if patients present within 3 h of an ischemic stroke. After 14 years of alteplase clinical research, evidence now suggests that the therapeutic treatment window can be expanded 4.5 h, but this is not formally approved by the FDA. Even though there remains a significant risk of intracerebral hemorrhage associated with alteplase administration, there is an increased chance of favorable outcome with tPA treatment. Over the last 30 years, the use of preclinical models has assisted with the search for new effective treatments for stroke, but there has been difficulty with the translation of efficacy from animals to humans. Current research focuses on the development of new and potentially useful thrombolytics, neuroprotective agents, and devices which are also being tested for efficacy in preclinical and clinical trials. One model in particular, the rabbit small clot embolic stroke model (RSCEM) which was developed to test tPA for efficacy, remains the only preclinical model used to gain FDA approval of a therapeutic for stroke. Correlative analyses from existing preclinical translational studies and clinical trials indicate that there is a therapeutic window ratio (ARR) of 2.43-3 between the RSCEM and AIS patients. In conclusion, the RSCEM can be used as an effective translational tool to gauge the clinical potential of new treatments