Congenital thyrotoxicosis in premature infants

OBJECTIVES Graves' disease (GD) complicates 0.1% to 0.2% of pregnancies, but congenital thyrotoxicosis is rare occurring in one in 70 of these pregnancies independent of maternal disease status. Antenatal prediction of affected infants is imprecise; however, maternal history, coupled with a high maternal serum TSH receptor binding immunoglobulin index (TBII) predict adverse neonatal outcome. Mortality is reported to be as high as 25% in affected infants and would therefore be expected to be higher in premature infants. This study illustrates that in sick, premature, extreme low birth weight (ELBW) or intrauterine growth retarded (IUGR) infants, the diagnosis maybe overlooked especially in the absence of antenatal risk assessment and management of thyrotoxicosis in this setting is complex. DESIGN and PATIENTS The records of premature neonates born at the three main maternity units in Brisbane, between January 1996 and July 1998 diagnosed with congenital thyrotoxicosis were reviewed. Data were recorded on gestational age, birth weight (B Wt), maternal thyroid history and current status, and neonatal course. Thyroid function and TBII status was assessed using standard biochemical assays. RESULTS Seven neonates from five pregnancies were identified (four female, three male). Mean gestational age was 30 week (25-36 week) and median B Wt was 1.96 kg (0.50-2.62 kg). Only one mother received formal antenatal counselling by a paediatric endocrine service and had a TBII (54%) measured prior to delivery. Three of five mothers had elevated TBII measured after diagnosis in their offspring (57%, 65%, 83%) and in one mother, a TBII was not performed. All mothers were biochemically euthyroid at delivery. Mean age at diagnosis was 9 days (1-16 days) and mean age at commencement of treatment was 12 days (7-26 days). Two infants received propylthiouracil and five received a combination of carbimazole and propranolol. Pour became biochemically hypothyroid, in three this resolved with cessation of the antithyroid drug (ATD), and one required ongoing T4 supplementation. Only one infant required treatment for cardiac failure and there were no deaths in this cohort. CONCLUSIONS This is a large series of extremely small and premature infants with neonatal thyrotoxicosis. Presentation was nonspecific. The diagnosis was delayed because of low birth weight, prematurity, multiple birth and/or an unrecognized maternal history of Graves' disease. The treatment of neonatal thyrotoxicosis was difficult in these extreme law birth weight infants yet no infant died and significant morbidity was confined to high output cardiac failure in one infant. With antenatal recognition of past or active Graves' disease, assessment of maternal TSH receptor binding immunoglobulin index prior to delivery and postnatal monitoring of cord TSH and venous fT4 and TSH on days 4 and 7 rapid treatment of affected infants may have further reduced neonatal morbidity.

Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation

The microphthalmia transcription factor (MITF), a basic-helix-loop-helix zipper factor, regulates distinct target genes in several cell types. We hypothesized that interaction with the Ets family factor PU.1, whose expression is limited to hematopoietic cells, might be necessary for activation of target genes like tartrate-resistant acid phosphatase (TRAP) in osteoclasts. Several lines of evidence were consistent with this model. The combination of MITF and PU.1 synergistically activated the TRAP promoter in transient assays. This activation was dependent on intact binding sites for both factors in the TRAP promoter. MITF and PU.1 physically interacted when coexpressed in COS cells or in vitro when purified recombinant proteins were studied. The minimal regions of MITF and PU.1 required for the interaction were the basic-helix-loop-helix zipper domain and the Ets DNA binding domain, respectively. Significantly, mice heterozygous for both the mutant mi allele and a PU.1 null allele developed osteopetrosis early in life which resolved with age. The size and number of osteoclasts were not altered in the double heterozygous mutant mice, indicating that the defect lies in mature osteoclast function. Taken in total, the results afford an example of how lineage-specific gene regulation can be achieved by the combinatorial action of two broadly expressed transcription factors.

Detection and description of non-linear interdependence in normal multichannel human EEG data

Objectives: This study examines human scalp electroencephalographic (EEG) data for evidence of non-linear interdependence between posterior channels. The spectral and phase properties of those epochs of EEG exhibiting non-linear interdependence are studied. Methods: Scalp EEG data was collected from 40 healthy subjects. A technique for the detection of non-linear interdependence was applied to 2.048 s segments of posterior bipolar electrode data. Amplitude-adjusted phase-randomized surrogate data was used to statistically determine which EEG epochs exhibited non-linear interdependence. Results: Statistically significant evidence of non-linear interactions were evident in 2.9% (eyes open) to 4.8% (eyes closed) of the epochs. In the eyes-open recordings, these epochs exhibited a peak in the spectral and cross-spectral density functions at about 10 Hz. Two types of EEG epochs are evident in the eyes-closed recordings; one type exhibits a peak in the spectral density and cross-spectrum at 8 Hz. The other type has increased spectral and cross-spectral power across faster frequencies. Epochs identified as exhibiting non-linear interdependence display a tendency towards phase interdependencies across and between a broad range of frequencies. Conclusions: Non-linear interdependence is detectable in a small number of multichannel EEG epochs, and makes a contribution to the alpha rhythm. Non-linear interdependence produces spatially distributed activity that exhibits phase synchronization between oscillations present at different frequencies. The possible physiological significance of these findings are discussed with reference to the dynamical properties of neural systems and the role of synchronous activity in the neocortex. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Patchy populations in stochastic environments: Critical number of patches for persistence

We introduce a model for the dynamics of a patchy population in a stochastic environment and derive a criterion for its persistence. This criterion is based on the geometric mean (GM) through time of the spatial-arithmetic mean of growth rates. For the population to persist, the GM has to be greater than or equal to1. The GM increases with the number of patches (because the sampling error is reduced) and decreases with both the variance and the spatial covariance of growth rates. We derive analytical expressions for the minimum number of patches (and the maximum harvesting rate) required for the persistence of the population. As the magnitude of environmental fluctuations increases, the number of patches required for persistence increases, and the fraction of individuals that can be harvested decreases. The novelty of our approach is that we focus on Malthusian local population dynamics with high dispersal and strong environmental variability from year to year. Unlike previous models of patchy populations that assume an infinite number of patches, we focus specifically on the effect that the number of patches has on population persistence. Our work is therefore directly relevant to patchily distributed organisms that are restricted to a small number of habitat patches.

Set-valued Markov chains and negative semitrajectories of discretized dynamical systems

Computer simulation of dynamical systems involves a phase space which is the finite set of machine arithmetic. Rounding state values of the continuous system to this grid yields a spatially discrete dynamical system, often with different dynamical behaviour. Discretization of an invertible smooth system gives a system with set-valued negative semitrajectories. As the grid is refined, asymptotic behaviour of the semitrajectories follows probabilistic laws which correspond to a set-valued Markov chain, whose transition probabilities can be explicitly calculated. The results are illustrated for two-dimensional dynamical systems obtained by discretization of fractional linear transformations of the unit disc in the complex plane.

Quasimode theory of quantum optical processes in photonic band gap materials

This paper deals with atomic systems coupled to a structured reservoir of quantum EM field modes, with particular relevance to atoms interacting with the field in photonic band gap materials. The case of high Q cavities has been treated elsewhere using Fano diagonalization based on a quasimode approach, showing that the cavity quasimodes are responsible for pseudomodes introduced to treat non-Markovian behaviour. The paper considers a simple model of a photonic band gap case, where the spatially dependent permittivity consists of a constant term plus a small spatially periodic term that leads to a narrow band gap in the spectrum of mode frequencies. Most treatments of photonic band gap materials are based on the true modes, obtained numerically by solving the Helmholtz equation for the actual spatially periodic permittivity. Here the field modes are first treated in terms of a simpler quasimode approach, in which the quasimodes are plane waves associated with the constant permittivity term. Couplings between the quasimodes occur owing to the small periodic term in the permittivity, with selection rules for the coupled modes being related to the reciprocal lattice vectors. This produces a field Hamiltonian in quasimode form. A matrix diagonalization method may be applied to relate true mode annihilation operators to those for quasimodes. The atomic transitions are coupled to all the quasimodes, and the true mode atom-EM field coupling constants (one-photon Rabi frequencies) are related to those for the quasimodes and also expressions are obtained for the true mode density. The results for the one-photon Rabi frequencies differ from those assumed in other work. Expressions for atomic decay rates are obtained using the Fermi Golden rule, although these are valid only well away from the band gaps.

Dynamics of a strongly driven two-component Bose-Einstein condensate

We consider a two-component Bose-Einstein condensate in two spatially localized modes of a double-well potential, with periodic modulation of the tunnel coupling between the two modes. We treat the driven quantum field using a two-mode expansion and define the quantum dynamics in terms of the Floquet Operator for the time periodic Hamiltonian of the system. It has been shown that the corresponding semiclassical mean-field dynamics can exhibit regions of regular and chaotic motion. We show here that the quantum dynamics can exhibit dynamical tunneling between regions of regular motion, centered on fixed points (resonances) of the semiclassical dynamics.

Separating the quantum sidebands of an optical field

In this paper we investigate the quantum optics of a double-ended optical cavity. We show that an impedance matched, far-detuned cavity can be used to separate the positive and negative sidebands of a field. The 'missing' sideband will be replaced by the equivalent sideband incident on the cavity from the other direction. This technique can be used to convert the quantum correlations between the sidebands of the incident fields into quantum correlations between the two spatially distinct output fields. We show that, under certain experimental conditions, the fields emerging from the cavity will display entanglement.

Reconciling paleodistribution models and comparative phylogeography in the Wet Tropics rainforest land snail Gnarosophia bellendenkerensis (Brazier 1875)

Comparative phylogeography has proved useful for investigating biological responses to past climate change and is strongest when combined with extrinsic hypotheses derived from the fossil record or geology. However, the rarity of species with sufficient, spatially explicit fossil evidence restricts the application of this method. Here, we develop an alternative approach in which spatial models of predicted species distributions under serial paleoclimates are compared with a molecular phylogeography, in this case for a snail endemic to the rainforests of North Queensland, Australia. We also compare the phylogeography of the snail to those from several endemic vertebrates and use consilience across all of these approaches to enhance biogeographical inference for this rainforest fauna. The snail mtDNA phylogeography is consistent with predictions from paleoclimate modeling in relation to the location and size of climatic refugia through the late Pleistocene-Holocene and broad patterns of extinction and recolonization. There is general agreement between quantitative estimates of population expansion from sequence data (using likelihood and coalescent methods) vs. distributional modeling. The snail phylogeography represents a composite of both common and idiosyncratic patterns seen among vertebrates, reflecting the geographically finer scale of persistence and subdivision in the snail. In general, this multifaceted approach, combining spatially explicit paleoclimatological models and comparative phylogeography, provides a powerful approach to locating historical refugia and understanding species' responses to them.

Violation of multiparticle Bell inequalities for low- and high-flux parametric amplification using both vacuum and entangled input states

We show how polarization measurements on the output fields generated by parametric down conversion will reveal a violation of multiparticle Bell inequalities, in the regime of both low- and high-output intensity. In this case, each spatially separated system, upon which a measurement is performed, is comprised of more than one particle. In view of the formal analogy with spin systems, the proposal provides an opportunity to test the predictions of quantum mechanics for spatially separated higher spin states. Here the quantum behavior possible even where measurements are performed on systems of large quantum (particle) number may be demonstrated. Our proposal applies to both vacuum-state signal and idler inputs, and also to the quantum-injected parametric amplifier as studied by De Martini The effect of detector inefficiencies is included, and weaker Bell-Clauser-Horne inequalities are derived to enable realistic tests of local hidden variables with auxiliary assumptions for the multiparticle situation.

Lanczos subspace time-independent wave packet calculations of S(D-1)+H-2 reactive scattering

In this paper. we present the results of quantum dynamical simulations of the S (D-1) + H-2 insertion reaction on a newly developed potential energy surface (J. Chem. Phys. 2001, 114, 320). State-to-state reaction probabilities. product state distributions, and initial-state resolved cumulative reaction probabilities from a given incoming reactant channel are obtained from a time-independent wave packet analysis, performed within a single Lanczos subspace. Integral reaction cross sections are then estimated by J-shifting method and compared with the results from molecular beam experiment and QCT calculations.

Chebyshev real wave packet propagation: H+O-2 (J=0) state-to-state reactive scattering calculations

In this paper we explore the relative performance of two recently developed wave packet methodologies for reactive scattering, namely the real wave packet Chebyshev domain propagation of Gray and Balint-Kurti [J. Chem. Phys. 108, 950 (1998)] and the Lanczos subspace wave packet approach of Smith [J. Chem. Phys. 116, 2354 (2002); Chem. Phys. Lett. 336, 149 (2001)]. In the former method, a modified Schrodinger equation is employed to propagate the real part of the wave packet via the well-known Chebyshev iteration. While the time-dependent wave packet from the modified Schrodinger equation is different from that obtained using the standard Schrodinger equation, time-to-energy Fourier transformation yields wave functions which differ only trivially by normalization. In the Lanczos subspace approach the linear system of equations defining the action of the Green operator may be solved via either time-dependent or time-independent methods, both of which are extremely efficient due to the simple tridiagonal structure of the Hamiltonian in the Lanczos representation. The two different wave packet methods are applied to three dimensional reactive scattering of H+O-2 (total J=0). State-to-state reaction probabilities, product state distributions, as well as initial-state-resolved cumulative reaction probabilities are examined. (C) 2002 American Institute of Physics.

Branching processes and computational collapse of discretized unimodal mappings

In computer simulations of smooth dynamical systems, the original phase space is replaced by machine arithmetic, which is a finite set. The resulting spatially discretized dynamical systems do not inherit all functional properties of the original systems, such as surjectivity and existence of absolutely continuous invariant measures. This can lead to computational collapse to fixed points or short cycles. The paper studies loss of such properties in spatial discretizations of dynamical systems induced by unimodal mappings of the unit interval. The problem reduces to studying set-valued negative semitrajectories of the discretized system. As the grid is refined, the asymptotic behavior of the cardinality structure of the semitrajectories follows probabilistic laws corresponding to a branching process. The transition probabilities of this process are explicitly calculated. These results are illustrated by the example of the discretized logistic mapping.

Virulence of Streptococcus pneumoniae: PsaA mutants are hypersensitive to oxidative stress

psaA encodes a 37-kDa pneumococcal lipoprotein which is part of an ABC Mn(II) transport complex. Streptococcus pneumoniae D39 psaA mutants have previously been shown to be significantly less virulent than wild-type D39, but the mechanism underlying the attenuation has not been resolved. In this study, we have shown that psaA and psaD mutants are highly sensitive to oxidative stress, i.e., to superoxide and hydrogen peroxide, which might explain why they are less virulent than the wild-type strain. Our investigations revealed altered expression of the key oxidative-stress response enzymes superoxide dismutase and NADH oxidase in psaA and psaD mutants, suggesting that PsaA and PsaD may play important roles in the regulation of expression of oxidative-stress response enzymes and intracellular redox homeostasis.

Acute stress hyperglycemia in cats is associated with struggling and increased concentrations of lactate and norepinephrine

We characterized the changes in blood glucose concentrations in healthy cats exposed to a short stressor and determined the associations between glucose concentrations, behavioral indicators of stress, and blood variables implicated in stress hyperglycemia (plasma glucose, lactate, insulin, glucagon, cortisol, epinephrine, and norepinephrine concentrations). Twenty healthy adult cats with normal glucose tolerance had a 5-minute spray bath. Struggling and vocalization were the most frequent behavioral responses. There was a strong relationship between struggling and concentrations of glucose and lactate. Glucose and lactate concentrations increased rapidly and significantly in all cats in response to bathing, with peak concentrations occurring at the end of the bath (glucose baseline 83 mg/dL, mean peak 162 mg/dL; lactate baseline 6.3 mg/dL, mean peak 64.0 mg/dL). Glucose response resolved within 90 minutes in 12 of the 20 cats. Changes in mean glucose concentrations were strongly correlated with changes in mean lactate (r =.84; P