Combined-channel instantaneous frequency analysis for audio source separation based on comodulation

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references (p. 295-303).Normal human listeners have a remarkable ability to focus on a single sound or speaker of interest and to block out competing sound sources. Individuals with hearing impairments, on the other hand, often experience great difficulty in noisy environments. The goal of our research is to develop novel signal processing methods inspired by neural auditory processing that can improve current speech separation systems. These could potentially be of use as assistive devices for the hearing impaired, and in many other communications applications. Our focus is the monaural case where spatial information is not available. Much perceptual evidence indicates that detecting common amplitude and frequency variation in acoustic signals plays an important role in the separation process. The physical mechanisms of sound generation in many sources cause common onsets/offsets and correlated increases/decreases in both amplitude and frequency among the spectral components of an individual source, which can potentially serve as a distinct signature. However, harnessing these common modulation patterns is difficult because when spectral components of competing sources overlap within the bandwidth of a single auditory filter, the modulation envelope of the resultant waveform resembles that of neither source. To overcome this, for the coherent, constant-frequency AM case, we derive a set of matrix equations which describes the mixture, and we prove that there exists a unique factorization under certain constraints. These constraints provide insight into the importance of onset cues in source separation. We develop algorithms for solving the system in those cases in which a unique solution exists. This work has direct bearing on the general theory of non-negative matrix factorization which has recently been applied to various problems in biology and learning. For the general, incoherent, AM and FM case, the situation is far more complex because constructive and destructive interference between sources causes amplitude fluctuations within channels that obscures the modulation patterns of individual sources.(cont.) Motivated by the importance of temporal processing in the auditory system, and specifically, the use of extrema, we explore novel methods for estimating instantaneous amplitude, frequency, and phase of mixtures of sinusoids by comparing the location of local maxima of waveforms from various frequency channels. By using an overlapping exponential filter bank model with properties resembling the cochlea, and combining information from multiple frequency bands, we are able to achieve extremely high frequency and time resolution. This allows us to isolate and track the behavior of individual spectral components which can be compared and grouped with others of like type. Our work includes both computational and analytic approaches to the general problem. Two suites of tests were performed. The first were comparative evaluations of three filter-bank-based algorithms on sets of harmonic-like signals with constant frequencies. One of these algorithms was selected for further performance tests on more complex waveforms, including AM and FM signals of various types, harmonic sets in noise, and actual recordings of male and female speakers, both individual and mixed. For the frequency-varying case, initial results of signal analysis with our methods appear to resolve individual sidebands of single harmonics on short time scales, and raise interesting conceptual questions on how to define, use and interpret the concept of instantaneous frequency. Based on our results, we revisit a number of questions in current auditory research, including the need for both rate and place coding, the asymmetrical shapes of auditory filters, and a possible explanation for the deficit of the hearing impaired in noise.by Barry David Jacobson.Ph.D

Book Reviews

Reviews of the following books: Island in Time: A Natural and Human History of the Islands of Maine by Philip W. Conkling; A Seafaring Legacy: The Photographs, Diaries and Memorabilia of a Maine Sea Captain and His Wife by Julianna FreeHand; Coming of Age on Damariscove Island, Maine by Carl R. Griffin III and Alaric Faulkner; The Identity of the St. Francis Indians by Gordon M. Day; Soldiers, Sailors and Patriots of the Revolutionary War: Maine by Carleton E. Fisher and Sue K. Fisher

Quality of Vitamin K Antagonist Control and 1-Year Outcomes in Patients with Atrial Fibrillation: A Global Perspective from the GARFIELD-AF Registry.

AIMS: Vitamin K antagonists (VKAs) need to be individually dosed. International guidelines recommend a target range of international normalised ratio (INR) of 2.0-3.0 for stroke prevention in atrial fibrillation (AF). We analysed the time in this therapeutic range (TTR) of VKA-treated patients with newly diagnosed AF in the ongoing, global, observational registry GARFIELD-AF. Taking TTR as a measure of the quality of patient management, we analysed its relationship with 1-year outcomes, including stroke/systemic embolism (SE), major bleeding, and all-cause mortality. METHODS AND RESULTS: TTR was calculated for 9934 patients using 136,082 INR measurements during 1-year follow-up. The mean TTR was 55.0%; values were similar for different VKAs. 5851 (58.9%) patients had TTR<65%; 4083 (41.1%) TTR≥65%. The proportion of patients with TTR≥65% varied from 16.7% in Asia to 49.4% in Europe. There was a 2.6-fold increase in the risk of stroke/SE, 1.5-fold increase in the risk of major bleeding, and 2.4-fold increase in the risk of all-cause mortality with TTR<65% versus ≥65% after adjusting for potential confounders. The population attributable fraction, i.e. the proportion of events attributable to suboptimal anticoagulation among VKA users, was 47.7% for stroke/SE, 16.7% for major bleeding, and 45.4% for all-cause mortality. In patients with TTR<65%, the risk of first stroke/SE was highest in the first 4 months and decreased thereafter (test for trend, p = 0.021). In these patients, the risk of first major bleed declined during follow-up (p = 0.005), whereas in patients with TTR≥65%, the risk increased over time (p = 0.027). CONCLUSION: A large proportion of patients with AF had poor VKA control and these patients had higher risks of stroke/SE, major bleeding, and all-cause mortality. Our data suggest that there is room for improvement of VKA control in routine clinical practice and that this could substantially reduce adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01090362

Evidence-based patient choice: a prostate cancer decision aid in plain language

BACKGROUND: Decision aids (DA) to assist patients in evaluating treatment options and sharing in decision making have proliferated in recent years. Most require high literacy and do not use plain language principles. We describe one of the first attempts to design a decision aid using principles from reading research and document design. The plain language DA prototype addressed treatment decisions for localized prostate cancer. Evaluation assessed impact on knowledge, decisions, and discussions with doctors in men newly diagnosed with prostate cancer. METHODS: Document development steps included preparing an evidence-based DA in standard medical parlance, iteratively translating it to emphasize shared decision making and plain language in three formats (booklet, Internet, and audio-tape). Scientific review of medical content was integrated with expert health literacy review of document structure and design. Formative evaluation methods included focus groups (n = 4) and survey of a new sample of men newly diagnosed with prostate cancer (n = 60), compared with historical controls (n = 184). RESULTS: A transparent description of the development process and design elements is reported. Formative evaluation among newly diagnosed prostate cancer patients found the DA to be clear and useful in reaching a decision. Newly diagnosed patients reported more discussions with doctors about treatment options, and showed increases in knowledge of side effects of radiation therapy. CONCLUSION: The plain language DA presenting medical evidence in text and numerical formats appears acceptable and useful in decision-making about localized prostate cancer treatment. Further testing should evaluate the impact of all three media on decisions made and quality of life in the survivorship period, especially among very low literacy men

Coeliac plexus radiosurgery for pain management in patients with advanced cancer : study protocol for a phase II clinical trial

Introduction: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer. Methods and analysis: A single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association. Ethics and dissemination: Ethic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications. Trial registration number: NCT03323489

Rethinking energy, climate and security: a critical analysis of energy security in the US

Understanding the complicated relationship between energy, climate and security is vital both to the study of international relations and to ensure the continued survival of a world increasingly threatened by environmental change. Climate change is largely caused by burning fossil fuels for energy, but while discussions on the climate consider the role of energy, energy security debates largely overlook climate concerns. This article traces the separation between energy and climate through an analysis of US energy security discourse and policy. It shows that energy security is continually constructed as national security, which enables very particular policy choices and prioritises it above climate concerns. Thus, in many cases, policies undertaken in the name of energy security contribute directly to climate insecurity. The article argues that the failure to consider securing the climate as inherently linked to energy security is not just problematic, but, given global warming, potentially harmful. Consequently, any approach to dealing with climate change has to begin by rethinking energy security and security more broadly, as national (energy) security politics no longer provides security in any meaningful sense

What Stimulates Researchers to Make Their Research Usable? Towards an Openness Approach

Ambiguity surrounding the effect of external engagement on academic research has raised questions about what motivates researchers to collaborate with third parties. We argue that what matters for society is research that can be absorbed by users. We define openness as a willingness by researchers to make research more usable by external partners by responding to external influences in their own research practices. We ask what kinds of characteristics define those researchers who are more open to creating usable knowledge. Our empirical study analyses a sample of 1583 researchers working at the Spanish Council for Scientific Research (CSIC). Results demonstrate that it is personal factors (academic identity and past experience) that determine which researchers have open behaviours. The paper concludes that policies to encourage external engagement should focus on experiences which legitimate and validate knowledge produced through user encounters, both at the academic formation career stage as well as through providing ongoing opportunities to engage with third parties.The data used for this study comes from the IMPACTO project funded by the Spanish Council for Scientific Research - CSIC (Ref. 200410E639). The work also benefited from a mobility grant awarded by Eu-Spri Forum to Julia Olmos Penuela & Paul Benneworth for her visiting research to the Center of Higher Education Policy Studies. Finally, Julia Olmos Penuela also benefited from a post-doctoral grant funded by the Generalitat Valenciana (APOSTD-2014-A-006).Olmos-Peñuela, J.; Benneworth, P.; Castro-Martínez, E. (2015). What Stimulates Researchers to Make Their Research Usable? Towards an Openness Approach. 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Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group