Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children

BACKGROUND: Descriptions of the pharmacokinetics and metabolism of morphine and its metabolites in young children are scant. Previous studies have not differentiated the effects of size from those related to age during infancy. METHODS: Postoperative children 0-3 yr old were given an intravenous loading dose of morphine hydrochloride (100 micro g kg(-1) in 2 min) followed by either an intravenous morphine infusion of 10 micro g h(-1) kg(-1) (n=92) or 3-hourly intravenous morphine boluses of 30 micro g kg(-1) (n=92). Additional morphine (5 micro g kg(-1)) every 10 min was given if the visual analogue (VAS, 0-10) pain score was >/=4. Arterial blood (1.4 ml) was sampled within 5 min of the loading dose and at 6, 12 and 24 h for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). The disposition of morphine and formation clearances of morphine base to its glucuronide metabolites and their elimination clearances were estimated using non-linear mixed effects models. RESULTS: The analysis used 1856 concentration observations from 184 subjects. Population parameter estimates and their variability (%) for a one-compartment, first-order elimination model were as follows: volume of distribution 136 (59.3) litres, formation clearance to M3G 64.3 (58.8) litres h(-1), formation clearance to M6G 3.63 (82.2) litres h(-1), morphine clearance by other routes 3.12 litres h(-1) per 70 kg, elimination clearance of M3G 17.4 (43.0) litres h(-1), elimination clearance of M6G 5.8 (73.8) litres h(-1). All parameters are standardized to a 70 kg person using allometric 3/4 power models and reflect fully mature adult values. The volume of distribution increased exponentially with a maturation half-life of 26 days from 83 litres per 70 kg at birth; formation clearance to M3G and M6G increased with a maturation half-life of 88.3 days from 10.8 and 0.61 litres h(-1) per 70 kg respectively at birth. Metabolite formation decreased with increased serum bilirubin concentration. Metabolite clearance increased with age (maturation half-life 129 days), and appeared to be similar to that described for glomerular filtration rate maturation in infants. CONCLUSION: M3G is the predominant metabolite of morphine in young children and total body morphine clearance is 80% that of adult values by 6 months. A mean steady-state serum concentration of 10 ng ml(-1) can be achieved in children after non-cardiac surgery in an intensive care unit with a morphine hydrochloride infusion of 5 micro g h(-1) kg(-1) at birth (term neonates), 8.5 micro g h(-1) kg(-1) at 1 month, 13.5 micro g h(-1) kg(-1) at 3 months and 18 micro g h(-1) kg(-1) at 1 year and 16 micro g h(-1) kg(-1) for 1- to 3-yr-old children

Flux Creep and Flux Jumping

We consider the flux jump instability of the Bean's critical state arising in the flux creep regime in type-II superconductors. We find the flux jump field, $B_j$, that determines the superconducting state stability criterion. We calculate the dependence of $B_j$ on the external magnetic field ramp rate, $\dot B_e$. We demonstrate that under the conditions typical for most of the magnetization experiments the slope of the current-voltage curve in the flux creep regime determines the stability of the Bean's critical state, {\it i.e.}, the value of $B_j$. We show that a flux jump can be preceded by the magneto-thermal oscillations and find the frequency of these oscillations as a function of $\dot B_e$.Comment: 7 pages, ReVTeX, 2 figures attached as postscript file

Understorey plant community and light availability in conifer plantations and natural hardwood forests in Taiwan

Questions: What are the effects of replacing mixed species natural forests with Cryptomeria japonica plantations on understorey plant functional and species diversity? What is the role of the understorey light environment in determining understorey diversity and community in the two types of forest? Location: Subtropical northeast Taiwan. Methods: We examined light environments using hemispherical photography, and diversity and composition of understorey plants of a 35‐yr C. japonica plantation and an adjacent natural hardwood forest. Results: Understorey plant species richness was similar in the two forests, but the communities were different; only 18 of the 91 recorded understorey plant species occurred in both forests. Relative abundance of plants among different functional groups differed between the two forests. Relative numbers of shade‐tolerant and shade‐intolerant seedling individuals were also different between the two forest types with only one shade‐intolerant seedling in the plantation compared to 23 seedlings belonging to two species in the natural forest. In the natural forest 11 species of tree seedling were found, while in the plantation only five were found, and the seedling density was only one third of that in the natural forest. Across plots in both forests, understorey plant richness and diversity were negatively correlated with direct sunlight but not indirect sunlight, possibly because direct light plays a more important role in understorey plant growth. Conclusions: We report lower species and functional diversity and higher light availability in a natural hardwood forest than an adjacent 30‐yr C. japonica plantation, possibly due to the increased dominance of shade‐intolerant species associated with higher light availability. To maintain plant diversity, management efforts must be made to prevent localized losses of shade‐adapted understorey plants

Momentum flux density, kinetic energy density and their fluctuations for one-dimensional confined gases of non-interacting fermions

We present a Green's function method for the evaluation of the particle density profile and of the higher moments of the one-body density matrix in a mesoscopic system of N Fermi particles moving independently in a linear potential. The usefulness of the method is illustrated by applications to a Fermi gas confined in a harmonic potential well, for which we evaluate the momentum flux and kinetic energy densities as well as their quantal mean-square fluctuations. We also study some properties of the kinetic energy functional E_{kin}[n(x)] in the same system. Whereas a local approximation to the kinetic energy density yields a multi-valued function, an exact single-valued relationship between the density derivative of E_{kin}[n(x)] and the particle density n(x) is demonstrated and evaluated for various values of the number of particles in the system.Comment: 10 pages, 5 figure

Surface Effects in Magnetic Microtraps

We have investigated Bose-Einstein condensates and ultra cold atoms in the vicinity of a surface of a magnetic microtrap. The atoms are prepared along copper conductors at distances to the surface between 300 um and 20 um. In this range, the lifetime decreases from 20 s to 0.7 s showing a linear dependence on the distance to the surface. The atoms manifest a weak thermal coupling to the surface, with measured heating rates remaining below 500 nK/s. In addition, we observe a periodic fragmentation of the condensate and thermal clouds when the surface is approached.Comment: 4 pages, 4 figures; v2: corrected references; v3: final versio

Stability of Repulsive Bose-Einstein Condensates in a Periodic Potential

The cubic nonlinear Schr\"odinger equation with repulsive nonlinearity and an elliptic function potential models a quasi-one-dimensional repulsive dilute gas Bose-Einstein condensate trapped in a standing light wave. New families of stationary solutions are presented. Some of these solutions have neither an analog in the linear Schr\"odinger equation nor in the integrable nonlinear Schr\"odinger equation. Their stability is examined using analytic and numerical methods. All trivial-phase stable solutions are deformations of the ground state of the linear Schr\"odinger equation. Our results show that a large number of condensed atoms is sufficient to form a stable, periodic condensate. Physically, this implies stability of states near the Thomas-Fermi limit.Comment: 12 pages, 17 figure

Highly anisotropic Bose-Einstein condensates: crossover to lower dimensionality

We develop a simple analytical model based on a variational method to explain the properties of trapped cylindrically symmetric Bose-Einstein condensates (BEC) of varying degrees of anisotropy well into regimes of effective one dimension (1D) and effective two dimension (2D). Our results are accurate in regimes where the Thomas-Fermi approximation breaks down and they are shown to be in agreement with recent experimental data.Comment: 4 pages, 2 figures; significantly more new material added; title and author-list changed due to changes in conten

The Low Energy π π\pi\,\pi Amplitude to One and Two Loops

The low-energy $\pi\pi$ amplitude is computed explicitly to two-loop accuracy in the chiral expansion. It depends only on six independent (combinations of) low-energy constants which are not fixed by chiral symmetry. Four of these constants are determined {\it via} sum rules which are evaluated using $\pi\pi$ scattering data at higher energies. Dependence of the low-energy phase shifts and of the threshold parameters on the remaining two constants (called $\alpha$ and $\beta$) are discussed and compared to the existing data from $K_{l4}$ experiments. Using generalised $\chi$PT, the constants $\alpha$ and $\beta$ are related to fundamental QCD parameters such as the quark condensate $\langle 0|\bar{q}q|0\rangle$ and the quark mass ratio $m_s/\widehat{m}$. It is shown that forthcoming accurate low-energy $\pi\pi$ data can be used to provide, for the first time, experimental evidence in favour of or against the existence of a large quark-antiquark condensate in the QCD vacuum.Comment: 61 pages, LaTeX, 10 figures in separate tarred, compressed and uuencoded Postscript fil

The Aharonov-Bohm effect for an exciton

We study theoretically the exciton absorption on a ring shreded by a magnetic flux. For the case when the attraction between electron and hole is short-ranged we get an exact solution of the problem. We demonstrate that, despite the electrical neutrality of the exciton, both the spectral position of the exciton peak in the absorption, and the corresponding oscillator strength oscillate with magnetic flux with a period $\Phi_0$---the universal flux quantum. The origin of the effect is the finite probability for electron and hole, created by a photon at the same point, to tunnel in the opposite directions and meet each other on the opposite side of the ring.Comment: 13 RevTeX 3.0 pages plus 4 EPS-figures, changes include updated references and an improved chapter on possible experimental realization

Modelling of strain effects in manganite films

Thickness dependence and strain effects in films of $La_{1-x}A_xMnO_3$ perovskites are analyzed in the colossal magnetoresistance regime. The calculations are based on a generalization of a variational approach previously proposed for the study of manganite bulk. It is found that a reduction in the thickness of the film causes a decrease of critical temperature and magnetization, and an increase of resistivity at low temperatures. The strain is introduced through the modifications of in-plane and out-of-plane electron hopping amplitudes due to substrate-induced distortions of the film unit cell. The strain effects on the transition temperature and transport properties are in good agreement with experimental data only if the dependence of the hopping matrix elements on the $Mn-O-Mn$ bond angle is properly taken into account. Finally variations of the electron-phonon coupling linked to the presence of strain turn out important in influencing the balance of coexisting phases in the filmComment: 7 figures. To be published on Physical Review