First Passage Time Densities in Non-Markovian Models with Subthreshold Oscillations

Motivated by the dynamics of resonant neurons we consider a differentiable, non-Markovian random process $x(t)$ and particularly the time after which it will reach a certain level $x_b$. The probability density of this first passage time is expressed as infinite series of integrals over joint probability densities of $x$ and its velocity $\dot{x}$. Approximating higher order terms of this series through the lower order ones leads to closed expressions in the cases of vanishing and moderate correlations between subsequent crossings of $x_b$. For a linear oscillator driven by white or coloured Gaussian noise, which models a resonant neuron, we show that these approximations reproduce the complex structures of the first passage time densities characteristic for the underdamped dynamics, where Markovian approximations (giving monotonous first passage time distribution) fail

Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids

SummaryBackgroundA recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls.ObjectiveThe purpose of the current study was to evaluate whether there was an increased risk of new onset diabetes mellitus or hyperglycaemia among patients with asthma or COPD treated with inhaled corticosteroids.MethodsA retrospective analysis evaluated all double-blind, placebo-controlled, trials in patients ≥4 years of age involving budesonide or budesonide/formoterol in asthma (26 trials; budesonide: n = 9067; placebo: n = 5926), and in COPD (8 trials; budesonide: n = 4616; non-ICS: n = 3643). A secondary dataset evaluated all double-blind, controlled trials in asthma involving the use of inhaled corticosteroids (60 trials; budesonide: n = 33,496; fluticasone: n = 2773).ResultsIn the primary asthma dataset, the occurrence of diabetes mellitus/hyperglycaemia adverse events (AEs) was 0.13% for budesonide and 0.13% for placebo (HR 0.98 [95% CI: 0.38–2.50], p = 0.96) and serious adverse events (SAEs) was 0% for budesonide and 0.05% for placebo. In the secondary dataset, the occurrence of diabetes/hyperglycaemia as AE and SAE was 0.19% and 0.03%, respectively. In the COPD dataset, the occurrence of diabetes mellitus/hyperglycaemia AEs was 1.3% for budesonide and 1.2% for non-ICS (HR 0.99 [95% CI: 0.67–1.46], p = 0.96) and SAEs was 0.1% for budesonide and 0.03% for non-ICS.Conclusion and clinical relevanceTreatment with inhaled corticosteroids in patients with asthma or COPD was not associated with increased risk of new onset diabetes mellitus or hyperglycaemia

Investigation of the electroplastic effect using nanoindentation

A promising approach to deform metallic-intermetallic composite materials is the application of electric current pulses during the deformation process to achieve a lower yield strength and enhanced elongation to fracture. This is known as the electroplastic effect. In this work, a novel setup to study the electroplastic effect during nanoindentation on individual phases and well-defined interfaces was developed. Using a eutectic Al-Al2Cu alloy as a model material, electroplastic nanoindentation results were directly compared with macroscopic electroplastic compression tests. The results of the micro- and macroscopic investigations reveal current induced displacement shifts and stress drops, respectively, with the first displacement shift/stress drop being higher than the subsequent ones. A higher current intensity, higher loading rate and larger pulsing interval all cause increased displacement shifts. This observation, in conjunction with the fact that the first displacement shift is highest, strongly indicates that de-pinning of dislocations from obstacles dominates the mechanical response, rather than solely thermal effects

Communications Biophysics

Contains reports on three research projects.United States Air Force (Contract AF19(602)-4112

Spectra of Discrete Schr\"odinger Operators with Primitive Invertible Substitution Potentials

We study the spectral properties of discrete Schr\"odinger operators with potentials given by primitive invertible substitution sequences (or by Sturmian sequences whose rotation angle has an eventually periodic continued fraction expansion, a strictly larger class than primitive invertible substitution sequences). It is known that operators from this family have spectra which are Cantor sets of zero Lebesgue measure. We show that the Hausdorff dimension of this set tends to $1$ as coupling constant $\lambda$ tends to $0$. Moreover, we also show that at small coupling constant, all gaps allowed by the gap labeling theorem are open and furthermore open linearly with respect to $\lambda$. Additionally, we show that, in the small coupling regime, the density of states measure for an operator in this family is exact dimensional. The dimension of the density of states measure is strictly smaller than the Hausdorff dimension of the spectrum and tends to $1$ as $\lambda$ tends to $0$

Communications Biophysics

Contains reports on five research projects.National Science Foundation (Grant G-16526)National Institutes of Health (Grant MH-04737-02)

Cosmological Implications of Neutrinos

The lectures describe several cosmological effects produced by neutrinos. Upper and lower cosmological limits on neutrino mass are derived. The role that neutrinos may play in formation of large scale structure of the universe is described and neutrino mass limits are presented. Effects of neutrinos on cosmological background radiation and on big bang nucleosynthesis are discussed. Limits on the number of neutrino flavors and mass/mixing are given.Comment: 41 page, 7 figures; lectures presented at ITEP Winter School, February, 2002; to be published in the Proceeding

Probing Unstable Massive Neutrinos with Current Cosmic Microwave Background Observations

The pattern of anisotropies in the Cosmic Microwave Background depends upon the masses and lifetimes of the three neutrino species. A neutrino species of mass greater than 10 eV with lifetime between 10^{13} sec and 10^{17} sec leaves a very distinct signature (due to the integrated Sachs-Wolfe effect): the anisotropies at large angles are predicted to be comparable to those on degree scales. Present data exclude such a possibility and hence this region of parameter space. For $m_\nu \simeq 30$ eV, $\tau \simeq 10^{13}$ sec, we find an interesting possibility: the Integrated Sachs Wolfe peak produced by the decaying neutrino in low-$\Omega$ models mimics the acoustic peak expected in an $\Omega = 1$ model.Comment: 5 pages, 4 figure

Communications Biophysics

Contains reports on four research projects.U.S. Air Force under Contract AF19(604)-411

Predictors of Development of Diabetes in Patients With Chronic Heart Failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Program

OBJECTIVE: The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.<p></p> RESEARCH DESIGN AND METHODS: A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses.<p></p> RESULTS: Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P &#60; 0.0001), higher BMI (OR 1.64 per 1 SD increase; P &#60; 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes.<p></p> CONCLUSIONS: In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures