Overtone-based pitch selection in hermit thrush song: Unexpected convergence with scale construction in human music

Many human musical scales, including the diatonic major scale prevalent in Western music, are built partially or entirely from intervals (ratios between adjacent frequencies) corresponding to small-integer proportions drawn from the harmonic series. Scientists have long debated the extent to which principles of scale generation in human music are biologically or culturally determined. Data from animal “song” may provide new insights into this discussion. Here, by examining pitch relationships using both a simple linear regression model and a Bayesian generative model, we show that most songs of the hermit thrush (Catharus guttatus) favor simple frequency ratios derived from the harmonic (or overtone) series. Furthermore, we show that this frequency selection results not from physical constraints governing peripheral production mechanisms but from active selection at a central level. These data provide the most rigorous empirical evidence to date of a bird song that makes use of the same mathematical principles that underlie Western and many non-Western musical scales, demonstrating surprising convergence between human and animal “song cultures.” Although there is no evidence that the songs of most bird species follow the overtone series, our findings add to a small but growing body of research showing that a preference for small-integer frequency ratios is not unique to humans. These findings thus have important implications for current debates about the origins of human musical systems and may call for a reevaluation of existing theories of musical consonance based on specific human vocal characteristics.Many human musical scales, including the diatonic major scale prevalent in Western music, are built partially or entirely from intervals (ratios between adjacent frequencies) corresponding to small-integer ratios drawn from the harmonic series (1). A long-running debate concerns the extent to which principles underlying the structure of human musical scales derive from biological aspects of auditory perception and/or vocal production or are historical cultural “accidents” (2–4). The songs of nonhuman animals, such as birds or whales, potentially offer a valuable perspective on this debate. On the one hand, features of human music that are culturally bound, or dependent on specific characteristics of the human voice or auditory system, should be absent in animal vocalizations. On the other hand, aspects of human music observed in the vocalizations of other species seem likely to be partially determined by general physical or biological constraints rather than solely by cultural practices. Such shared features would complement recent research suggesting that common motor constraints shape both human song and that of some bird species (5).The physical principles underlying vocal production in songbirds are well understood (6–10) and do not differ fundamentally from those of other vertebrates. Sound is produced by tissue vibrations in the syrinx, a bird-specific organ located at the base of the trachea. Flow-driven vibrations of fleshy membranes within the syrinx (in songbirds, the medial and lateral labia) generate a periodic source signal that is filtered by the air column within the trachea and mouth and then emitted to the environment. These principles are important in formulating various alternative hypotheses considered below.Naturalists have long wondered whether birdsong could be said to have musical properties (11–13). However, early studies on pitch selection tended to be anecdotal, based on a small sample size, or lacking in analytical rigor. Two more recent studies specifically comparing pitch selection in bird song and human musical scales concluded that birdsong does not make preferential use of musical intervals found in commonly used Western musical scales (14, 15). However, because these studies each only examined one species [the white-throated sparrow (Zonotrichia albicollis) and the nightingale wren (Microcerculus philomela), respectively], a conclusion that birdsong in general does not exhibit musical properties seems premature. Indeed, other studies have shown preferential use of consonant intervals in tropical boubou shrikes (Laniarius aethiopicus) (16) and musician wrens (Cyphorhinus arada) (17), although in the first case no rigorous statistical analysis was presented.Here, we investigated songs of the hermit thrush (Catharus guttatus), a medium-sized North American songbird whose famously “musical”-sounding song has attracted the attention of ornithologists and musicians alike (18) but has not yet been subjected to detailed pitch analysis. Its songs are composed of elements (the smallest unit of song construction, seen as continuous uninterrupted traces on spectrograms) that may exhibit either a variable pitch, such as trills and slides, or a stable pitch—pure, non-frequency-modulated, “flutelike” sounds. These stable sounds, which we refer to as “notes” (Fig. 1), are characterized by strong fundamental frequencies and very weak higher harmonics, making them ideally suited for an analysis of pitch relationships (15). Males typically sing 6–10 different song types, defined as nearly identical sequences of elements, durations, and frequencies. In a number of early- and mid-20th-century studies, hermit thrush song was variously attributed with use of major, minor, and pentatonic scales (19, 20) and claimed to follow the overtone series (21). However, these early studies again suffered from small sample sizes and anecdotal reporting and were not based on rigorous acoustic analysis. More recent hermit thrush studies have focused on regional differences and song-type ordering, rather than pitch selection (22, 23).Open in a separate windowFig. 1.Song of the hermit thrush (C. guttatus). One song type of a single male hermit thrush, illustrating the various elements that can be observed in songs of this species. Only “notes” (elements with stable pitch) were analyzed in this study because the other element types have no clearly defined or measurable pitch.Here we tested the overtone hypothesis, which predicts that the frequencies of the individual song notes are integer multiples (harmonics) of an implied (but not actually sung) base frequency (hereafter f_i). This hypothesis seems plausible because, unlike some previous claims, it does not attribute human-specific music-theoretical concepts to hermit thrush song. Moreover, the subjective impression of trained musicians listening to hermit thrush songs (played at one-sixth of the original speed to shift the speed and frequency of the songs into a range more suitable for human hearing) was that most notes indeed seemed to follow an overtone series (see Fig. 2 and Audio File S1 for the corresponding sound example). However, determining whether a set of notes are harmonics of a frequency not present in the set requires a rigorous procedure to estimate and evaluate f_i. To this end, we used two different statistical approaches, an ordinary least-squares regression model and a generative Bayesian estimator. Both approaches were used to test the hypothesis that a song is an exchangeable sequence of frequencies that are integer multiples of some implied f_i, versus the null hypothesis that songs are generated by drawing frequencies out of a random log-normal distribution (see Materials and Methods for details). By using a Bayesian approach in addition to the least-squares regression model we evaluate whether our analyses represent a rigorous test of our overtone hypothesis and not simply a post hoc explanation that minimizes an error measure by “memorizing” the data. These properties make the Bayesian evaluation statistically more rigorous than least-squares fitting.Open in a separate windowFig. 2.Frequency distribution of a hermit thrush song compared with an overtone series. (A) Notes of a hermit thrush song. (B) The same notes rearranged in ascending order to show how they correspond to overtones 3, 4, 5, and 6 of an overtone series fitted to the frequencies corresponding to these notes (the complete stacked overtone series is shown on the right).     

Midterm clinical and radiographic results of the medial pivot total knee system

Purpose

The ADVANCE® Medial Pivot Knee System was designed with a highly congruent medial compartment and a less conforming lateral compartment to more closely mimic the kinematics of the normal knee. The purpose of this study was to evaluate the midterm clinical and radiographic outcomes of this total knee arthroplasty (TKA) system.

Methods

Between January 1998 and December 2006, 421 primary TKAs were performed in 373 subjects using this system and a surgical technique that resects the posterior cruciate ligament. Of these, 365 TKAs in 320 subjects were available for a follow-up visit occurring at a mean of 5.3 years. Subjects were evaluated using Knee Society Scores, range of motion, and radiographic review.

Results

The average Knee Society clinical score was 95.5 at final follow-up, with 358 (98 %) TKAs having excellent or good results. Range of motion increased from a preoperative mean of 115 to 119° at final follow-up. Component survivorship, excluding revisions for infection or trauma, was 96.6 % at five years.

Conclusions

This study demonstrates subjects implanted with the ADVANCE® Medial Pivot Knee System achieved satisfactory clinical and radiographic midterm outcomes.     

The Economic Burden of Ischemic Stroke and Major Hemorrhage in Medicare Beneficiaries with Nonvalvular Atrial Fibrillation: A Retrospective Claims Analysis

Background

Understanding the economic implications of oral anticoagulation therapy requires careful consideration of the risks and costs of stroke and major hemorrhage. The majority of patients with atrial fibrillation (AF) are aged ≥65 years, so focusing on the Medicare population is reasonable when discussing the risk for stroke.

Objective

To examine the relative economic burden associated with stroke and major hemorrhage among Medicare beneficiaries who are newly diagnosed with nonvalvular atrial fibrillation (NVAF).

Methods

This study was a retrospective analysis of a 5% sample of Medicare claims data for patients with NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12 months before the first (index) claim for AF in 2007 (baseline period) were identified and were classified into 4 cohorts during a 12-month follow-up period after the index date. These cohorts included (1) no claims for ischemic stroke or major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic stroke and ≥1 claims for major hemorrhage (hemorrhage only); (3) ≥1 claims for ischemic stroke and no major hemorrhage claims (stroke only); and (4) ≥1 claims each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1-year mean postindex total all-cause healthcare costs adjusted by the Centers for Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were compared among the study cohorts. Results: Of the 9455 eligible patients included in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3% (N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow-up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per patient for the ischemic stroke only and the hemorrhage only cohorts, respectively, compared with $35,474 per patient for those without hemorrhage or stroke claims. After adjustment for HCC risk score, the mean incremental costs for patients with stroke claims only and hemorrhage claims only, relative to those without stroke or hemorrhage claims, were $26,776 (95% confidence interval [CI], $20,785-$32,767; P <.001) and $26,168 (95% CI, $20,375-$31,961; P <.001), respectively.

Conclusion

The economic burden of managing patients with NVAF who experience ischemic stroke and hemorrhage were similarly significant during the first year after a diagnosis of NVAF. The burden of major bleeding complications on patients, clinicians, and payers should not be overlooked, and these complications should be considered in conjunction with the cost-savings associated with ischemic stroke risk reduction in future cost-benefit evaluations of oral anticoagulation therapy.Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia.1,2 The most recent estimates (published in 2013) of the prevalence of AF in the United States are for 2010 and range from 2.7 million to 6.1 million.3,4 The prevalence of AF doubles with each decade of life after the age of 60 years and occurs in approximately 10% of the US population aged ≥80 years.5–7 A recent study estimates that the number of patients with AF in the United States could potentially reach 12.1 million by 20303; other estimates range from 5.6 million to 12 million patients with AF by 2050.4Patients with AF have an approximate 5-fold increased risk for stroke compared with patients in normal sinus rhythm.4 Furthermore, the percentage of strokes that can be attributed to AF increases steeply with age, with rates of 1.5% in patients aged 50 to 59 years and 23.5% in those aged 80 to 89 years.4 The term “nonvalvular atrial fibrillation” (NVAF) is used to describe cases of AF that occur in the absence of rheumatic mitral valve disease, mitral valve repair, or a prosthetic heart valve.8 NVAF affects approximately 85% of the overall population with AF and is a substantial medical burden for Medicare beneficiaries (aged ≥65 years) in the United States.9,10The current evidence-based clinical guidelines recommend the use of oral anticoagulation in patients with NVAF who are at an intermediate to high risk for stroke.8,11 Although the efficacy of oral anticoagulation therapy to prevent stroke in patients with NVAF is well-established, it is also associated with a risk of bleeding.12–15 Understanding the relative economic burdens of stroke and major hemorrhage is important when considering the costs and benefits of anticoagulation therapy.Several studies have reported the incremental costs associated with stroke alone or with hemorrhage alone using different NVAF payer populations (ie, commercial or Medicare), and a few recent studies have provided incremental cost data for stroke and hemorrhage for the Medicare population, reporting significant incremental costs in the year after the stroke or hemorrhage index dates.7,16–20 Other studies have analyzed the incremental costs associated with stroke alone or with hemorrhage alone, or have analyzed these costs for a commercial population with NVAF.21–24 Most of these studies were done in separate patient populations and different time periods, making assessment of the relative economic burden of stroke versus bleeding difficult. By contrast, our study provides the cost estimates for these 2 conditions simultaneously based on the same patient population, which allows a more appropriate comparison of the economic implication of these 2 major consequences of oral anticoagulation therapy for the prevention of stroke among patients with NVAF.The prespecified objective in our study was to assess the relative economic burden (including Medicare Part D costs) associated with ischemic stroke and with major hemorrhagic events (ie, intracranial and gastrointestinal [GI] bleeding) among Medicare beneficiaries with newly diagnosed NVAF in the 12 months after the NVAF index diagnosis.     

Covalent structure of human haptoglobin: a serine protease homolog.

The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.     

CHLOROQUINE RESISTANCE IN MALARIA: A DEFICIENCY OF CHLOROQUINE BINDING

Chloroquine-(14)C was used to study the processes which concentrate chloroquine in mouse red blood cells infected with chloroquine-sensitive or with chloroquine-resistant Plasmodium berghei. The initial rates of uptake and exchange of chloroquine-(14)C were both too fast to measure, yet large concentration gradients were maintained by the cells. When red blood cells were exposed to 10(-8)M chloroquine at 22 degrees C, with pH between 7.2 and 7.4, steady-state gradients of chloroquine-(14)C were approximately 600:1 (cells:medium) for cells infected with chloroquine-sensitive parasites, 100:1 for cells comparably infected with chloroquine-resistant parasites, and 14:1 for uninfected cells. The processes responsible for these gradients were saturable, in agreement with the proposal of chloroquine binding to cellular constituents. No degradation of chloroquine was detected.The major difference between the chloroquine-sensitive and -resistant parasites was deficiency of high-affinity binding of chloroquine by cells infected with chloroquine-resistant parasites. This deficiency explains the reduced ability of chloroquine-resistant parasites to concentrate chloroquine, and it suggests that chloroquine resistance is due to a decrease in the number, affinity, or accessibility of chloroquine receptor sites on a constituent of the malaria parasite.     

Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass

POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low-density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk.     

Serum protein profile alterations in hemodialysis patients

BACKGROUND: Serum protein profiling patterns can reflect the pathological state of a patient and therefore may be useful for clinical diagnostics. Here, we present results from a pilot study of proteomic expression patterns in hemodialysis patients designed to evaluate the range of serum proteomic alterations in this population. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was used to analyze serum obtained from patients on periodic hemodialysis treatment and healthy controls. Serum samples from patients and controls were first fractionated into six eluants on a strong anion exchange column, followed by application to four array chemistries representing cation exchange, anion exchange, metal affinity and hydrophobic surfaces. A total of 144 SELDI-TOF-MS spectra were obtained from each serum sample. RESULTS: The overall profiles of the patient and control samples were consistent and reproducible. However, 30 well-defined protein differences were observed; 15 proteins were elevated and 15 were decreased in patients compared to controls. Serum from 1 patient exhibited novel protein peaks suggesting possible additional changes due to a secondary disease process. CONCLUSION: SELDI-TOF-MS demonstrated consistent serum protein profile differences between patients and controls. Similarity in protein profiles among dialysis patients suggests that patient physiological responses to end-stage renal disease and/or dialysis therapy have a major effect on serum protein profiles.     

The Centers for Medicare and Medicaid Services (CMS) Community-Acquired Pneumonia Core Measures Lead to Unnecessary Antibiotic Administration by Emergency Physicians

Objectives: The objectives were to assess emergency physician (EP) understanding of the Centers for Medicare and Medicaid Services (CMS) core measures for community‐acquired pneumonia (CAP) guidelines and to determine their self‐reported effect on antibiotic prescribing patterns. Methods: A convenience sample of EPs from five medical centers in North Carolina was anonymously surveyed via a Web‐based instrument. Participants indicated their level of understanding of the CMS CAP guidelines and the effects on their prescribing patterns for antibiotics. Results: A total of 121 EPs completed the study instrument (81%). All respondents were aware of the CMS CAP guidelines. Of these, 95% (95% confidence interval [CI] = 92% to 98%) correctly understood the time‐based guidelines for antibiotic administration, although 24% (95% CI = 17% to 31%) incorrectly identified the onset of this time period. Nearly all physicians (96%; 95% CI = 93% to 99%) reported institutional commitment to meet these core measures, and 84% (95% CI = 78% to 90%) stated that they had a department‐based CAP protocol. More than half of the respondents (55%; 95% CI = 47% to 70%) reported prescribing antibiotics to patients they did not believe had pneumonia in an effort to comply with the CMS guidelines, and 42% (95% CI = 34% to 50%) of these stated that they did so more than three times per month. Only 40% (95% CI = 32% to 48%) of respondents indicated a belief that the guidelines improve patient care. Of those, this was believed to occur by increasing pneumonia awareness (60%; 95% CI = 52% to 68%) and improving hospital processes when pneumonia is suspected (86%; 95% CI = 80% to 92%). Conclusions: Emergency physicians demonstrate awareness of the current CMS CAP guidelines. Most physicians surveyed reported the presence of institutional protocols to increase compliance. More than half of EPs reported that they feel the guidelines led to unnecessary antibiotic usage for patients who are not suspected to have pneumonia. Only 40% of EPs believe that CAP awareness and expedient care resulting from these guidelines has improved overall pneumonia‐related patient care. Outcome‐based data for non–intensive care unit CAP patients are lacking, and EPs report that they prescribe antibiotics when they may not be necessary to comply with existing guidelines.     

Reliability and validity of disability questions for US Census 2000

OBJECTIVES: We investigated the validity and proxy reliability of 7 new disability questions from the 2000 US census ("Census 2000"). METHODS: A total of 131 people with disabilities and their proxies from St Louis, Mo, and Massachusetts were interviewed, and responses were compared for concordance. Responses also were compared with responses to questions from the Behavioral Risk Factor Surveillance System (BRFSS) and the Activities of Daily Living (ADL) instrument. RESULTS: Overall, proxies reported more impairment than did people with disabilities, and agreement was low (kappa = 0.24-0.55). Concordance was moderate between the census questions and their BRFSS and ADL counterparts. CONCLUSIONS: The Census 2000 questions may not provide an accurate profile of disability in America.