Bayesian nonparametric models for peak identification in MALDI-TOF mass spectroscopy

We present a novel nonparametric Bayesian approach based on L\'{e}vy Adaptive Regression Kernels (LARK) to model spectral data arising from MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time-of-Flight) mass spectrometry. This model-based approach provides identification and quantification of proteins through model parameters that are directly interpretable as the number of proteins, mass and abundance of proteins and peak resolution, while having the ability to adapt to unknown smoothness as in wavelet based methods. Informative prior distributions on resolution are key to distinguishing true peaks from background noise and resolving broad peaks into individual peaks for multiple protein species. Posterior distributions are obtained using a reversible jump Markov chain Monte Carlo algorithm and provide inference about the number of peaks (proteins), their masses and abundance. We show through simulation studies that the procedure has desirable true-positive and false-discovery rates. Finally, we illustrate the method on five example spectra: a blank spectrum, a spectrum with only the matrix of a low-molecular-weight substance used to embed target proteins, a spectrum with known proteins, and a single spectrum and average of ten spectra from an individual lung cancer patient.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS450 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

EVALUATING FACTORS INFLUENCING GROCERY STORE CHOICE

This paper analyzes consumer preferences toward grocery store choices given a set of attributes of stores. This information will then be used to make inferences on how the opening of a Wal-Mart supercenter would affect the other grocery stores in a small city.Consumer/Household Economics, Institutional and Behavioral Economics,

Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges

The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter

Bimodal release ondansetron for acute gastroenteritis among adolescents and adults: A randomized clinical trial

Importance: Vomiting resulting from acute gastroenteritis is commonly treated with intravenous antiemetics in acute care settings. If oral treatment were beneficial, patients might not need intravenous administered hydration or medication. Furthermore, a long-acting treatment could provide sustained relief from nausea and vomiting. Objective: To determine whether an experimental long-acting bimodal release ondansetron tablet decreases gastroenteritis-related vomiting and eliminates the need for intravenous therapy for 24 hours after administration. Design, Setting, and Participants: This placebo-controlled, double-blind, randomized clinical trial included patients from 19 emergency departments and 2 urgent care centers in the United States from December 8, 2014, to February 17, 2017. Patients 12 years and older with at least 2 vomiting episodes from presumed gastroenteritis in the previous 4 hours and symptoms with less than 36 hours\u27 duration were randomized using a 3:2 active to placebo ratio. Analyses were performed on an intent-to-treat basis and conducted from June 1, 2017, to November 1, 2017. Intervention: Bimodal release ondansetron tablet containing 6 mg of immediate release ondansetron and 18 mg of a 24-hour release matrix for a total of 24 mg of ondansetron. Main Outcomes and Measures: Treatment success was defined as no further vomiting, no need for rescue medication, and no intravenous hydration for 24 hours after bimodal release ondansetron administration. Results: Analysis included 321 patients (mean [SD] age, 29.0 [11.1] years; 195 [60.7%] women), with 192 patients in the bimodal release ondansetron group and 129 patients in the placebo group. Treatment successes were observed in 126 patients in the bimodal release ondansetron group (65.6%) compared with 70 patients in the placebo group (54.3%), with an 11.4% (95% CI, 0.3%-22.4%) absolute probability difference. The proportion of treatment success was 21% higher among patients who received bimodal release ondansetron compared with those who received a placebo (relative risk, 1.21; 95% CI, 1.00-1.46; P = .04). In an analysis including only patients with a discharge diagnosis of acute gastroenteritis and no major protocol violations, there were 123 treatment successes (69.5%) in the bimodal release ondansetron group compared with 67 treatment successes (54.9%) in the placebo group (relative risk, 1.27; 95% CI, 1.05-1.53; P = .01). Adverse effects were infrequent and similar to the known safety profile of ondansetron. Conclusions and Relevance: This randomized clinical trial found that a long-acting bimodal release oral ondansetron tablet was an effective antiemetic among adolescents and adults with moderate to severe vomiting from acute gastroenteritis. The drug benefits extended to 24 hours after administration. Bimodal release ondansetron may decrease the need for intravenous access and emergency department care to manage acute gastroenteritis. Trial Registration: ClinicalTrials.gov identifier: NCT02246439

Automated external cardioversion defibrillation monitoring in cardiac arrest: a randomized trial

<p>Abstract</p> <p>Background</p> <p>In-hospital cardiac arrest has a poor prognosis despite active electrocardiography monitoring. The initial rhythm of approximately 25% of in-hospital cardiopulmonary resuscitation (CPR) events is pulseless ventricular tachycardia/ventricular fibrillation (VT/VF). Early defibrillation is an independent predictor of survival in CPR events caused by VT/VF. The automated external cardioverter defibrillator (AECD) is a device attached by pads to the chest wall that monitors, detects, and within seconds, automatically delivers electric countershock to an appropriate tachyarrhythmia.</p> <p>Study Objectives</p> <p>• To evaluate safety of AECD monitoring in hospitalized patients.</p> <p>• To evaluate whether AECDs provide earlier defibrillation than hospital code teams.</p> <p>Methods</p> <p>The study is a prospective trial randomizing patients admitted to the telemetry ward to standard CPR (code team) or standard CPR plus AECD monitoring (PowerHeart CRM). The AECD is programmed to deliver one 150 J biphasic shock to patients in sustained VT/VF. Data is collected using the Utstein criteria for cardiac arrest. The primary endpoint is time-to-defibrillation; secondary outcomes include neurological status and survival to discharge, with 3-year follow-up.</p> <p>Results</p> <p>To date, 192 patients have been recruited in the time period between 10/10/2006 to 7/20/2007. A total of 3,655 hours of telemetry data have been analyzed in the AECD arm. The AECD has monitored ambulatory telemetry patients in sinus rhythm, sinus tachycardia, supraventricular tachycardia, atrial flutter or fibrillation, with premature ventricular complexes and non-sustained VT without delivery of inappropriate shocks. One patient experienced sustained VT during AECD monitoring, who was successfully defibrillated (17 seconds after meeting programmed criteria). There are no events to report in the control arm. The patient survived the event without neurological complications. During the same time period, mean time to shock for VT/VF cardiac arrest occurring outside the telemetry ward was 230 ± 50 seconds.</p> <p>Conclusion</p> <p>AECD monitoring is safe and likely results in earlier defibrillation than standard telemetry monitoring.</p> <p>Trial Registration</p> <p>National Institutes of Health registration ID: NCT00382928</p

Interpretation, translation and intercultural communication in refugee status determination procedures in the UK and France

This article explores the interplay between language and intercultural communication within refugee status determination procedures in the UK and France, using material taken from ethnographic research that involved a combination of participant observation, semi-structured interviews and documentary analysis in both countries over a two-year period (2007–2009). It is concerned, in particular, to examine the role played by interpreters in facilitating intercultural communication between asylum applicants and the different administrative and legal actors responsible for assessing or defending their claims. The first section provides an overview of refugee status determination procedures in the UK and France, introducing the main administrative and legal contexts of the asylum process within which interpreters operate in the two countries. The second section compares the organisation of interpreting services, codes of conduct for interpreters and institutional expectations about the nature of interpreters’ activity on the part of the relevant UK and French authorities. The third section then explores some of the practical dilemmas for interpreters and barriers to communication that exist in refugee status determination procedures in the two countries. The article concludes by emphasising the complex and active nature of the interpreter's role in UK and French refugee status determination procedures

The Whole Counsel of God: A Tribute to E. Herbert Nygren

Herb Nygren has served Taylor University faithfully for over twenty years. As chair of the Department of Biblical Studies, Christian Education, and Philosophy, he has modelled sound teaching and solid scholarship. Upon retirement, he leaves us a legacy of dedication, service, and love for Christ. The members of his department offer these essays as a small token of our esteem.https://pillars.taylor.edu/ayres-collection-books/1019/thumbnail.jp

Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits

Background and Purpose - Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32), encoded by PCK1, catalyzes the first committed step in gluconeogenesis. We previously showed that a -232C\u3eG promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance. We hypothesized that this polymorphism would be associated with carotid atherosclerosis in a sample of 150 aboriginal Canadians. Methods - Dependent variables were 2 distinct carotid traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and total carotid plaque volume (TPV) assessed using 3D ultrasound. Results - Multivariate analysis showed significant but opposite associations of PCK1 genotype with these traits. Specifically, subjects with the PCK1-232G/G genotype had more carotid IMT (0.80±0.02 versus 0.73±0.03 mm; P=0.007) but less TPV (0.10±0.09 versus 0.38±0.13; P=0.03) than subjects with other genotypes. Conclusions - The findings connect the key enzyme in gluconeogenesis with atherosclerosis. The meaning of the opposing associations of PCK1 genotype with IMT and TPV is unclear; more work is required to confirm whether these might be distinct quantitative traits with different biological determinants. © 2005 American Heart Association, Inc

Genetic variation in PPARG encoding peroxisome proliferator-activated receptor γ associated with carotid atherosclerosis

Background and Purpose-Peroxisome proliferator-activated receptor γ is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points. Methods-We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C\u3eT, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound. Results-Using multivariate analysis, we found that subjects with ≥ 1 PPARG A12 allele had less carotid IMT than others (0.72±0.03 versus 0.80±0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124±18.4 versus 65.1±23.7 mm3; P=0.0079), with no between-genotype difference in IMT. Conclusions-The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis

The effect of volume change and stack pressure on solid‐state battery cathodes

Solid-state lithium batteries may provide increased energy density and improved safety compared with Li-ion technology. However, in a solid-state composite cathode, mechanical degradation due to repeated cathode volume changes during cycling may occur, which may be partially mitigated by applying a significant, but often impractical, uniaxial stack pressure. Herein, we compare the behavior of composite electrodes based on Li4Ti5O12 (LTO) (negligible volume change) and Nb2O5 (+4% expansion) cycled at different stack pressures. The initial LTO capacity and retention are not affected by pressure but for Nb2O5, they are significantly lower when a stack pressure of &lt;2 MPa is applied, due to inter-particle cracking and solid-solid contact loss because of cyclic volume changes. This work confirms the importance of cathode mechanical stability and the stack pressures for long-term cyclability for solid-state batteries. This suggests that low volume-change cathode materials or a proper buffer layer are required for solid-state batteries, especially at low stack pressures