Prior Design for Dependent Dirichlet Processes: An Application to Marathon Modeling

This paper presents a novel application of Bayesian nonparametrics (BNP) for marathon data modeling. We make use of two well-known BNP priors, the single-p dependent Dirichlet process and the hierarchical Dirichlet process, in order to address two different problems. First, we study the impact of age, gender and environment on the runners’ performance. We derive a fair grading method that allows direct comparison of runners regardless of their age and gender. Unlike current grading systems, our approach is based not only on top world records, but on the performances of all runners. The presented methodology for comparison of densities can be adopted in many other applications straightforwardly, providing an interesting perspective to build dependent Dirichlet processes. Second, we analyze the running patterns of the marathoners in time, obtaining information that can be valuable for training purposes. We also show that these running patterns can be used to predict finishing time given intermediate interval measurements. We apply our models to New York City, Boston and London marathons

Infinite Factorial Finite State Machine for Blind Multiuser Channel Estimation

New communication standards need to deal with machine-to-machine communications, in which users may start or stop transmitting at any time in an asynchronous manner. Thus, the number of users is an unknown and time-varying parameter that needs to be accurately estimated in order to properly recover the symbols transmitted by all users in the system. In this paper, we address the problem of joint channel parameter and data estimation in a multiuser communication channel in which the number of transmitters is not known. For that purpose, we develop the infinite factorial finite state machine model, a Bayesian nonparametric model based on the Markov Indian buffet that allows for an unbounded number of transmitters with arbitrary channel length. We propose an inference algorithm that makes use of slice sampling and particle Gibbs with ancestor sampling. Our approach is fully blind as it does not require a prior channel estimation step, prior knowledge of the number of transmitters, or any signaling information. Our experimental results, loosely based on the LTE random access channel, show that the proposed approach can effectively recover the data-generating process for a wide range of scenarios, with varying number of transmitters, number of receivers, constellation order, channel length, and signal-to-noise ratio

Gout. Imaging of gout: findings and utility

Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation. Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques. Plain radiographs show typical changes only in advanced chronic gout. Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes. Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation. Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy

Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. Objectives We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. Methods Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload–induced calcium release activity of the mutant channel in HEK293 cells. Results We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload–induced calcium release activity under conditions that mimic catecholaminergic stress. Conclusion Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation

Efficacy and safety during extended treatment of lesinurad in combination with febuxostat in patients with tophaceous gout: CRYSTAL extension study

Abstract Background In gout, long-term urate-lowering therapy (ULT) promotes dissolution of tissue urate crystal deposits. However, no studies using combined xanthine oxidase inhibition and uricosuric ULT have focused on clinical outcomes or adverse events (AEs) beyond 12 months of therapy. Our objective in the present study was to examine efficacy and long-term safety in patients with tophaceous gout receiving febuxostat plus lesinurad as combination therapy. Methods Patients receiving combined lesinurad and febuxostat in the 12-month core CRYSTAL study continued at the same doses in the extension study (“200CONT”, “400CONT”), whereas those receiving only febuxostat 80 mg were randomized to lesinurad 200 or 400 mg with febuxostat (“200CROSS”, “400CROSS”). The primary endpoint was the proportion of patients experiencing complete resolution (CR) of at least one target tophus by extension month (EM) 12. The key secondary endpoint was mean rate of gout flares requiring treatment from the end of EM 2 to the end of EM 12. Secondary endpoints included reduction in the sum of areas for all target tophi. Safety assessments included AEs and laboratory data for the entire extension study (median length of lesinurad exposure, 800 days). Results Of 235 patients completing the core study, 196 (83.4%) enrolled in the extension: 200CONT (n = 64), 200CROSS (n = 33), 400CONT (n = 65), and 400CROSS (n = 34). At EM 12, 59.6%, 43.5%, 66.7%, and 50.0% of patients, respectively, had CR of at least one target tophus. The sum of areas for all target tophi was reduced by 76.4%, 58.1%, 77.5%, and 62.8%, respectively. The adjusted mean (SE) rates of gout flares requiring treatment from the end of EM 2 to the end of EM 12 were 0.6 (0.19), 1.3 (0.48), 0.2 (0.08), and 1.9 (0.93), respectively. Target sUA < 5.0 mg/dl was achieved by 77.1%, 79.2%, 88.5%, and 71.4% of patients, respectively. Exposure-adjusted incidence rates of treatment-emergent adverse events (TEAEs) and renal-related TEAEs in the core study were not increased with prolonged lesinurad exposure in the extension study. Conclusions Patients receiving lesinurad plus febuxostat therapy for 2 years continued to be at sUA target. Patients exhibited a progressive increase in CR of at least one target tophus, progressive reduction in tophus size, and reduction of gout flares requiring treatment over the second year, with AEs consistent with those observed in the core study. Trial registration ClinicalTrials.gov , NCT01510769 . Registered on 13 January 2012.https://deepblue.lib.umich.edu/bitstream/2027.42/146783/1/13075_2018_Article_1788.pd

Morphometric analysis of bite mark patterns caused by domestic dogs (Canis lupus familiaris) using dental wax registers

Dog bites are a known public health problem involving physical, mental and emotional traumas. From a forensic point of view, it has been stated that their morphological characters, and the intercanine and interincisive measurements, could allow a taxonomic and specific identification of the implicated animal. The aim of this study was to differentiate and identify the biological profile of a potential aggressor dog by analysing eight morphometric bite patterns belonging to three different dog breeds. The data obtained were analyzed following three categories: a) breeds; b) sexes among breeds; and c) sex within breed. Significant differences were detected among the variables (p <= 0.05), but only the maximum maxillary intercanines width (MaxCW) allowed a breed differentiation. The other variables allowed a differentiation between two breeds or one breed over the others. The principal components analysis (PCA) allowed visualizing the degree of dispersion and relationship among the scores. It showed three well-defined and separated breed groups, and different degrees of dispersion within and among breeds. The most important variable for such a differentiation was MaxCW. When considering sex among breeds for males, it showed a statistically significant difference, but only the diastema located between the third left mandibular, incisive and the left mandibular canine (C-I-ManL) allowed breed differentiation. For females, only MaxCW allowed a differentiation among breeds. The multivariate analysis permitted with a 95 % confidence interval, a breed and sex differentiation. Besides, the PCA models allowed classifying, identifying, separating and graphically showing the relationship among the variables. This made it possible to differentiate between breeds and sexes. Due to the large range of dog breeds around the world, this multivariate analysis could also help determining the dog's weight and size, narrowing down towards an approximate number of offending dogs, focussing on a certain kind of dog breed, and pinpointing any suspect dog

The Pic Protease of Enteroaggregative \u3cem\u3eEscherichia coli\u3c/em\u3e Promotes Intestinal Colonization and Growth in the Presence of Mucin

Enteroaggregative Escherichia coli (EAEC) is increasingly being recognized as a cause of diarrheal disease in diverse populations. No small animal model is currently available to study this pathogen. We report here that conventional mice orally inoculated with prototype EAEC strain 042 generally became colonized, though the abundance of organisms cultured from their stool varied substantially among individual animals. In contrast, mice whose water contained 5 g/liter streptomycin consistently became colonized at high levels (ca. 108 CFU/g of stool). Neither conventional nor streptomycin-treated mice developed clinical signs or histopathologic abnormalities. Using specific mutants in competition with the wild-type strain, we evaluated the contribution of several putative EAEC virulence factors to colonization of streptomycin-treated mice. Our data suggest that the dispersin surface protein and Pic, a serine protease autotransporter secreted by EAEC and Shigella flexneri, promote colonization of the mouse. In contrast, we found no role for the aggregative adherence fimbriae, the transcriptional activator AggR, or the surface factor termed Air (enteroaggregative immunoglobulin repeat protein). To study Pic further, we constructed a single nucleotide mutation in strain 042 which altered only the Pic catalytic serine (strain 042PicS258A). Fractionation of the tissue at 24 h and 3 days demonstrated an approximate 3-log10 difference between 042 and 042PicS258A in the lumen and mucus layer and adherent to tissue. Strains 042 and 042PicS258A adhered similarly to mouse tissue ex vivo. While no growth differences were observed in a continuous-flow anaerobic intestinal simulator system, the wild-type strain exhibited a growth advantage over 042PicS258A in a culture of cecal mucus and in cecal contents in vitro; this difference was manifest only after 6 h of growth. Moreover, enhanced growth of the wild type was observed in comparison with that of the mutant in minimal medium containing mucin but not in the absence of mucin. The data suggest a novel metabolic role for the Pic mucinase in EAEC colonization