Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification

Introduction: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric population specifically is unknown. We tested the performance of two SDAs on pediatric data from the US FDA Adverse Event Reporting System (FAERS) and investigated the impact of age stratification and age adjustment on the performance of SDAs. Methods: We tested the performance of two established SDAs: the proportional reporting ratio (PRR) and the empirical Bayes geometric mean (EBGM) on a pediatric dataset from FAERS (2004–2012). We compared the performance of the SDAs with a published pediatric-specific reference set by calculating diagnostic test-related statistics, including the area under the curve (AUC) of receiver operating characteristics. Impact of age stratification and age-adjustment on the performance of the SDAs was assessed. Age adjustment was performed by pooling (Mantel-Hanszel) stratum-specific estimates. Results: A total of 115,674 pediatric reports (patients aged 0–18 years) comprising 893,587 drug–event combinations (DECs) were analysed. Crude values of the AUC were similar for both SDAs: 0.731 (PRR) and 0.745 (EBGM). Stratification unmasked four DECs, e.g., ‘ibuprofen and thrombocytopenia’. Age adjustment did not improve performance. Conclusion: The performance of the two tested SDAs was similar in the pediatric population. Age adjustment does not improve performance and is therefore not recommended to be performed routinely. Stratification can reveal new associations, and therefore is recommended when either drug use is age-specific or when an age-specific risk is suspected

Collective excitations of trapped Bose condensates in the energy and time domains

A time-dependent method for calculating the collective excitation frequencies and densities of a trapped, inhomogeneous Bose-Einstein condensate with circulation is presented. The results are compared with time-independent solutions of the Bogoliubov-deGennes equations. The method is based on time-dependent linear-response theory combined with spectral analysis of moments of the excitation modes of interest. The technique is straightforward to apply, is extremely efficient in our implementation with parallel FFT methods, and produces highly accurate results. The method is suitable for general trap geometries, condensate flows and condensates permeated with vortex structures.Comment: 6 pages, 3 figures small typos fixe

Pandemic influenza vaccine & narcolepsy: Simulations on the potential impact of bias

Several studies have identified an association between PandemrixTM, an AS03 adjuvanted pandemic influenza A(H1N1) vaccine, and narcolepsy, a rare and under-diagnosed sleep disorder with a median onset-to-diagnosis interval of ten years. This paper reviews potential sources of bias in published studies and aims to provide, through simulation, methodological recommendations for assessment of vaccine safety signals. Our simulation study showed that in the absence of an association between the vaccine and the outcome, presence of detection bias and differential exposure misclassification could account for elevated risk estimates. These may play a major role, particularly in alert situations when observation times are limited and the disease has a long latency period. Estimates from the case-control design were less inflated than those from the cohort design when these biases were present. Overall, these simulations provide useful insights for the design and interpretation of future studies

Energetics and Possible Formation and Decay Mechanisms of Vortices in Helium Nanodroplets

The energy and angular momentum of both straight and curved vortex states of a helium nanodroplet are examined as a function of droplet size. For droplets in the size range of many experiments, it is found that during the pickup of heavy solutes, a significant fraction of events deposit sufficient energy and angular momentum to form a straight vortex line. Curved vortex lines exist down to nearly zero angular momentum and energy, and thus could in principle form in almost any collision. Further, the coalescence of smaller droplets during the cooling by expansion could also deposit sufficient angular momentum to form vortex lines. Despite their high energy, most vortices are predicted to be stable at the final temperature (0.38 K) of helium nanodroplets due to lack of decay channels that conserve both energy and angular momentum.Comment: 10 pages, 8 figures, RevTex 4, submitted to Phys. Rev.

Ideal Gases in Time-Dependent Traps

We investigate theoretically the properties of an ideal trapped gas in a time-dependent harmonic potential. Using a scaling formalism, we are able to present simple analytical results for two important classes of experiments: free expansion of the gas upon release of the trap; and the response of the gas to a harmonic modulation of the trapping potential is investigated. We present specific results relevant to current experiments on trapped Fermions.Comment: 5 pages, 3 eps figure

Instability of a Bose-Einstein Condensate with Attractive Interaction

We study the stability of a Bose-Einstein condensate of harmonically trapped atoms with negative scattering length, specifically lithium 7. Our method is to solve the time-dependent nonlinear Schrodinger equation numerically. For an isolated condensate, with no gain or loss, we find that the system is stable (apart from quantum tunneling) if the particle number N is less than a critical number N_c. For N > N_c, the system collapses to high-density clumps in a region near the center of the trap. The time for the onset of collapse is on the order of 1 trap period. Within numerical uncertainty, the results are consistent with the formation of a "black hole" of infinite density fluctuations, as predicted by Ueda and Huang. We obtain numerically N_c approximately 1251. We then include gain-loss mechanisms, i.e., the gain of atoms from a surrounding "thermal cloud", and the loss due to two- and three-body collisions. The number N now oscillates in a steady state, with a period of about 145 trap periods. We obtain N_c approximately 1260 as the maximum value in the oscillations.Comment: Email correspondence to [email protected] ; 18 pages and 9 EPS figures, using REVTeX and BoxedEPS macro

Vortices in superfluid trapped Fermi gases at zero temperature

We discuss various aspects of the vortex state of a dilute superfluid atomic Fermi gas at T=0. The energy of the vortex in a trapped gas is calculated and we provide an expression for the thermodynamic critical rotation frequency of the trap for its formation. Furthermore, we propose a method to detect the presence of a vortex by calculating the effect of its associated velocity field on the collective mode spectrum of the gas

Bose condensates in a harmonic trap near the critical temperature

The mean-field properties of finite-temperature Bose-Einstein gases confined in spherically symmetric harmonic traps are surveyed numerically. The solutions of the Gross-Pitaevskii (GP) and Hartree-Fock-Bogoliubov (HFB) equations for the condensate and low-lying quasiparticle excitations are calculated self-consistently using the discrete variable representation, while the most high-lying states are obtained with a local density approximation. Consistency of the theory for temperatures through the Bose condensation point requires that the thermodynamic chemical potential differ from the eigenvalue of the GP equation; the appropriate modifications lead to results that are continuous as a function of the particle interactions. The HFB equations are made gapless either by invoking the Popov approximation or by renormalizing the particle interactions. The latter approach effectively reduces the strength of the effective scattering length, increases the number of condensate atoms at each temperature, and raises the value of the transition temperature relative to the Popov approximation. The renormalization effect increases approximately with the log of the atom number, and is most pronounced at temperatures near the transition. Comparisons with the results of quantum Monte Carlo calculations and various local density approximations are presented, and experimental consequences are discussed.Comment: 15 pages, 11 embedded figures, revte

Entanglement, Bell Inequalities and Decoherence in Particle Physics

We demonstrate the relevance of entanglement, Bell inequalities and decoherence in particle physics. In particular, we study in detail the features of the ``strange'' $K^0 \bar K^0$ system as an example of entangled meson--antimeson systems. The analogies and differences to entangled spin--1/2 or photon systems are worked, the effects of a unitary time evolution of the meson system is demonstrated explicitly. After an introduction we present several types of Bell inequalities and show a remarkable connection to CP violation. We investigate the stability of entangled quantum systems pursuing the question how possible decoherence might arise due to the interaction of the system with its ``environment''. The decoherence is strikingly connected to the entanglement loss of common entanglement measures. Finally, some outlook of the field is presented.Comment: Lectures given at Quantum Coherence in Matter: from Quarks to Solids, 42. Internationale Universit\"atswochen f\"ur Theoretische Physik, Schladming, Austria, Feb. 28 -- March 6, 2004, submitted to Lecture Notes in Physics, Springer Verlag, 45 page

Mean-field description of collapsing and exploding Bose-Einstein condensates

We perform numerical simulation based on the time-dependent mean-field Gross-Pitaevskii equation to understand some aspects of a recent experiment by Donley et al. on the dynamics of collapsing and exploding Bose-Einstein condensates of $^{85}$Rb atoms. They manipulated the atomic interaction by an external magnetic field via a Feshbach resonance, thus changing the repulsive condensate into an attractive one and vice versa. In the actual experiment they changed suddenly the scattering length of atomic interaction from positive to a large negative value on a pre-formed condensate in an axially symmetric trap. Consequently, the condensate collapses and ejects atoms via explosion. We find that the present mean-field analysis can explain some aspects of the dynamics of the collapsing and exploding Bose-Einstein condensates.Comment: 9 Latex pages, 10 ps and eps files, version accepted in Physical Review A, minor changes mad