Factors Associated with Persistence with Teriparatide Therapy: Results from the DANCE Observational Study

Purpose. Determine patient-reported reasons for discontinuation with teriparatide. Methods. Patients taking teriparatide in a multicenter, prospective, and observational study were given three questionnaires: baseline, follow-up questionnaire 1 (QF1, 2 to 6 months), and follow-up questionnaire 2 (QF2, 12 months). Discontinuation reported at QF1 and QF2 was defined as “early” and “late,” respectively, and remaining patients were considered persistent. Cochran-Armitage trend test was used to identify factors associated with discontinuation. Results. Side effects, concern about improper use, injection difficulties, and several patient-perceived physician issues were associated with early discontinuation. Low patient-perceived importance of continuing treatment, side effects, difficulty paying, and low patient-perceived physician knowledge were associated with late discontinuation. The most common specific reasons selected for discontinuing treatment were “concerns about treatment outweighing the benefits” (n = 53) and “difficulty paying” (n = 47). Conclusions. Persistence with teriparatide is dependent on managing side effects, addressing financial challenges, proper training, and obtaining support from the healthcare provider

Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States

Background: High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods: We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009–2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results: In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009–2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of$1.0 B compared to PCV7. Conclusions: In a flu pandemic similar to the 2009–2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs

Experimental Implementation of the Quantum Baker's Map

This paper reports on the experimental implementation of the quantum baker's map via a three bit nuclear magnetic resonance (NMR) quantum information processor. The experiments tested the sensitivity of the quantum chaotic map to perturbations. In the first experiment, the map was iterated forward and then backwards to provide benchmarks for intrinsic errors and decoherence. In the second set of experiments, the least significant qubit was perturbed in between the iterations to test the sensitivity of the quantum chaotic map to applied perturbations. These experiments are used to investigate previous predicted properties of quantum chaotic dynamics.Comment: submitted to PR

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Determining the flux of methane into Hudson Canyon at the edge of methane clathrate hydrate stability

Author Posting. © American Geophysical Union, 2016. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 17 (2016): 3882–3892, doi:10.1002/2016GC006421.Methane seeps were investigated in Hudson Canyon, the largest shelf-break canyon on the northern U.S. Atlantic Margin. The seeps investigated are located at or updip of the nominal limit of methane clathrate hydrate stability. The acoustic identification of bubble streams was used to guide water column sampling in a 32 km2 region within the canyon's thalweg. By incorporating measurements of dissolved methane concentration with methane oxidation rates and current velocity into a steady state box model, the total emission of methane to the water column in this region was estimated to be 12 kmol methane per day (range: 6–24 kmol methane per day). These analyses suggest that the emitted methane is largely retained inside the canyon walls below 300 m water depth, and that it is aerobically oxidized to near completion within the larger extent of Hudson Canyon. Based on estimated methane emissions and measured oxidation rates, the oxidation of this methane to dissolved CO2 is expected to have minimal influences on seawater pH.National Science Foundation Grant Number: OCE-1318102; U.S. Department of Energy award Grant Numbers: DE-FE0013999 and NSF OCE-1352301, DOE-USGS, DE-FE0002911 and DE-FE00058062017-04-1

Matrix Models, Complex Geometry and Integrable Systems. I

We consider the simplest gauge theories given by one- and two- matrix integrals and concentrate on their stringy and geometric properties. We remind general integrable structure behind the matrix integrals and turn to the geometric properties of planar matrix models, demonstrating that they are universally described in terms of integrable systems directly related to the theory of complex curves. We study the main ingredients of this geometric picture, suggesting that it can be generalized beyond one complex dimension, and formulate them in terms of the quasiclassical integrable systems, solved by construction of tau-functions or prepotentials. The complex curves and tau-functions of one- and two- matrix models are discussed in detail.Comment: 52 pages, 19 figures, based on several lecture courses and the talks at "Complex geometry and string theory" and the Polivanov memorial seminar; misprints corrected, references adde

Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort

Bayesian Bounds on Parameter Estimation Accuracy for Compact Coalescing Binary Gravitational Wave Signals

A global network of laser interferometric gravitational wave detectors is projected to be in operation by around the turn of the century. Here, the noisy output of a single instrument is examined. A gravitational wave is assumed to have been detected in the data and we deal with the subsequent problem of parameter estimation. Specifically, we investigate theoretical lower bounds on the minimum mean-square errors associated with measuring the parameters of the inspiral waveform generated by an orbiting system of neutron stars/black holes. Three theoretical lower bounds on parameter estimation accuracy are considered: the Cramer-Rao bound (CRB); the Weiss-Weinstein bound (WWB); and the Ziv-Zakai bound (ZZB). We obtain the WWB and ZZB for the Newtonian-form of the coalescing binary waveform, and compare them with published CRB and numerical Monte-Carlo results. At large SNR, we find that the theoretical bounds are all identical and are attained by the Monte-Carlo results. As SNR gradually drops below 10, the WWB and ZZB are both found to provide increasingly tighter lower bounds than the CRB. However, at these levels of moderate SNR, there is a significant departure between all the bounds and the numerical Monte-Carlo results.Comment: 17 pages (LaTeX), 4 figures. Submitted to Physical Review

The refined biomimetic NeuroDigm GEL™ model of neuropathic pain in a mature rat [version 2; referees: 1 approved, 2 approved with reservations]

Background: Many humans suffering with chronic neuropathic pain have no objective evidence of an etiological lesion or disease. Frequently their persistent pain occurs after the healing of a soft tissue injury. Based on clinical observations over time, our hypothesis was that after an injury in mammals the process of tissue repair could cause chronic neural pain. Our objectives were to create the delayed onset of neuropathic pain in rats with minimal nerve trauma using a physiologic hydrogel, and characterize the rats’ responses to known analgesics and a targeted biologic.   Methods: In mature male Sprague Dawley rats (age 9.5 months) a percutaneous implant of tissue-derived hydrogel was placed in the musculofascial tunnel of the distal tibial nerve. Subcutaneous morphine (3 mg/kg), celecoxib (10 mg/kg), gabapentin (25 mg/kg) and duloxetine (10 mg/kg) were each screened in the model three times each over 5 months after pain behaviors developed. Sham and control groups were used in all screenings. A pilot study followed in which recombinant human erythropoietin (200 units) was injected by the GEL™ neural procedure site.   Results: The GEL group gradually developed mechanical hypersensitivity lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses demonstrated profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months, p ≤ 0.001. Histology of the GEL group tibial nerve revealed a site of focal neural remodeling, with neural regeneration, as found in nerve biopsies of patients with neuropathic pain.   Conclusion: The refined NeuroDigm GEL™ model induces a neural response resulting in robust neuropathic pain behavior. The analgesic responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin at the ectopic neural lesion appears to alleviate the persistent pain behavior in the GEL™ model rodents