Unifying Amplitude and Phase Analysis: A Compositional Data Approach to Functional Multivariate Mixed-Effects Modeling of Mandarin Chinese

Mandarin Chinese is characterized by being a tonal language; the pitch (or $F_0$) of its utterances carries considerable linguistic information. However, speech samples from different individuals are subject to changes in amplitude and phase which must be accounted for in any analysis which attempts to provide a linguistically meaningful description of the language. A joint model for amplitude, phase and duration is presented which combines elements from Functional Data Analysis, Compositional Data Analysis and Linear Mixed Effects Models. By decomposing functions via a functional principal component analysis, and connecting registration functions to compositional data analysis, a joint multivariate mixed effect model can be formulated which gives insights into the relationship between the different modes of variation as well as their dependence on linguistic and non-linguistic covariates. The model is applied to the COSPRO-1 data set, a comprehensive database of spoken Taiwanese Mandarin, containing approximately 50 thousand phonetically diverse sample $F_0$ contours (syllables), and reveals that phonetic information is jointly carried by both amplitude and phase variation.Comment: 49 pages, 13 figures, small changes to discussio

The role of the locus coeruleus in mediating the attentional blink: A neurocomputational theory.

The attentional blink refers to the transient impairment in perceiving the 2nd of 2 targets presented in close temporal proximity. In this article, the authors propose a neurobiological mechanism for this effect. The authors extend a recently developed computational model of the potentiating influence of the locus coeruleus-norepinephrine system on information processing and hypothesize that a refractoriness in the function of this system may account for the attentional blink. The model accurately simulates the time course of the attentional blink, including Lag 1 sparing. The theory also offers an account of the close relationship of the attentional blink to the electrophysiological P3 component. The authors report results from two behavioral experiments that support a critical prediction of their theory regarding the time course of Lag 1 sparing. Finally, the relationship between the authors' neurocomputational theory and existing cognitive theories of the attentional blink is discussed. Copyright 2005 by the American Psychological Association

Decision making, the P3, and the locus coeruleus-norepinephrine system.

Psychologists and neuroscientists have had a long-standing interest in the P3, a prominent component of the event-related brain potential. This review aims to integrate knowledge regarding the neural basis of the P3 and to elucidate its functional role in information processing. The authors review evidence suggesting that the P3 reflects phasic activity of the neuromodulatory locus coeruleus-norepinephrine (LC-NE) system. They discuss the P3 literature in the light of empirical findings and a recent theory regarding the information-processing function of the LC-NE phasic response. The theoretical framework emerging from this research synthesis suggests that the P3 reflects the response of the LC-NE system to the outcome of internal decision-making processes and the consequent effects of noradrenergic potentiation of information processing. Copyright 2005 by the American Psychological Association

Prognostic Impact of KRAS Mutation Subtypes in 677 Patients with Metastatic Lung Adenocarcinomas

BackgroundWe previously demonstrated that patients with metastatic KRAS mutant lung cancers have a shorter survival compared with patients with KRAS wild-type cancers. Recent reports have suggested different clinical outcomes and distinct activated signaling pathways depending on KRAS mutation subtype. To better understand the impact of KRAS mutation subtype, we analyzed data from 677 patients with KRAS mutant metastatic lung cancer.MethodsWe reviewed all patients with metastatic or recurrent lung cancers found to have KRAS mutations over a 6-year time period. We evaluated the associations among KRAS mutation type, clinical factors, and overall survival in univariate and multivariate analyses. Any significant findings were validated in an external multi-institution patient dataset.ResultsAmong 677 patients with KRAS mutant lung cancers (53 at codon 13, 624 at codon 12), there was no difference in overall survival for patients when comparing KRAS transition versus transversion mutations (p = 0.99), smoking status (p = 0.33), or when comparing specific amino acid substitutions (p = 0.20). In our dataset, patients with KRAS codon 13 mutant tumors (n = 53) had shorter overall survival compared with patients with codon 12 mutant tumors (n = 624) (1.1 versus 1.3 years, respectively; p = 0.009), and the findings were confirmed in a multivariate Cox model controlling for age, sex, and smoking status (hazard ratio: 1.52, 95% confidence interval: 1.11–2.08; p = 0.008). In an independent validation set of tumors from 682 patients with stage IV KRAS mutant lung cancers, there was no difference in survival between patients with KRAS codon 13 versus codon 12 mutations (1.0 versus 1.1 years, respectively; p = 0.41).ConclusionsAmong individuals with KRAS mutant metastatic lung cancers treated with conventional therapy, there are no apparent differences in outcome based on KRAS mutation subtype

Freedom, Servitude and Voluntary Labor

We present an economic framework to revisit and reframe some important debates over the nature of free versus unfree labor and the economic consequences of emancipation. We use a simple general equilibrium model in which labor can be either free or coerced and where land and labor will be exchanged on markets that can be competitive or manipulated or via other non-market collusive arrangements. By working with variants of the same basic model under different assumptions about initial economy-wide factor endowments and asset ownership we can compare equilibrium distributional outcomes under different institutional and contractual arrangements including markets with free labor and free tenancy, slavery, and tenancy arrangements with tied labor-service obligations. Analysis of these different contractual and organizational forms yields insights that accord with common sense, but that are often overlooked or downplayed in academic debates, particularly amongst economists

Final-State Phases in Charmed Meson Two-Body Nonleptonic Decays

Observed decay rates indicate large phase differences among the amplitudes for the charge states in $D \to \bar K \pi$ and $D \to \bar K^* \pi$ but relatively real amplitudes in the charge states for $D \to \bar K \rho$. This feature is traced using an SU(3) flavor analysis to a sign flip in the contribution of one of the amplitudes contributing to the latter processes in comparison with its contribution to the other two sets. This amplitude may be regarded as an effect of rescattering and is found to be of magnitude comparable to others contributing to charmed particle two-body nonleptonic decays.Comment: 19 pages, latex, 4 figures, to be submitted to Phys. Rev.

On Large Final-State Phases in Heavy Meson Decays

An attempt is made to identify circumstances under which the weak decays of $D$ and $B$ mesons may display large differences between eigenphases of strong final-state interactions. There are several cases in which rescattering from other final states appears to enhance decay rates with respect to estimates based on the factorization hypothesis.Comment: 24 pages, latex, 4 figures, to be submitted to Phys. Rev.

Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man’s risk of disease by 10% (OR 1.10 [1.04–1.16], p,261023), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p,161023), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p,0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.261025). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.This work was partially funded by the Portuguese Foundation for Science and Technology FCT/MCTES (PIDDAC) and co-financed by European funds (FEDER) through the COMPETE program, research grant PTDC/SAU-GMG/101229/2008. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by FCT. AML is the recipient of a postdoctoral fellowship from FCT (SFRH/BPD/73366/2010). CO is supported by a grant from the United States National Institutes of Health (R01 HD21244), JDS is supported by Damon Runyon Clinical Investigator Award, Alex's Lemonade Stand Foundation Epidemiology Award, and the Eunice Kennedy Shriver Children's Health Research Career Development Award NICHD 5K12HD001410. Support for humans studies and specimens were provided by the NIH/NIDDK George M. O'Brien Center for Kidney Disease Kidney Translational Research Core (P30DK079333) grant to Washington University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The incidence of Kawasaki disease using hospital admissions data for England 2006-2021

To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 - 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity, and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, SD = 3.2, 95% CI: 3.7-3.9). Incidence in children aged <5 years was 8.9 (95% CI: 8.6-9.2)/100 000 person-years; in children aged 5-9, 2.4 (95% CI: 2.3-2.6)/100 000 person-years; and in children aged 10-15, 0.6 (95% CI: 0.6-0.7). Male: female ratio was 1.5:1. Incidence was higher among non-White than White ethnicities (adjusted IRR 2.1 (2.0-2.2) for Asian, 3.0 (2.8-3.3) for Black and 4.5 (4.2-4.8) for other ethnicities). The incidence increased with socioeconomic deprivation; the adjusted IRR of the least deprived IMD quintile compared with the most deprived quintile was 0.81 (0.77-0.84). Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex, and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups