Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy

To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. Methods. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. Results. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (116.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1 %, P < 0.01). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (11975 vs: 1128 mg, P < 0.01). The incidence of FM with VPA doses greater than or equal to 1100 mg was 30.2% vs. 3.2% with doses < 1100 mg (P < 0.01). Conclusions. There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy. (C) 2004 Elsevier Ltd. All rights reserved.

Income Ranking and convergence with physical and human capital and income equality

This paper presents an overlapping generations model with physical and human capital and income inequality. It shows that inequality impedes output growth by directly harming capital accumulation and indirectly raising the ratio of physical to human capital. The convergence speed of output growth equals the lower of the convergence speeds of the relative capital ratio and inequality, and varies with initial states. Among economies with the same balanced growth rate but different initial income levels, the ranking of income can switch in favor of those starting from low inequality and a low ratio of physical to human capital, particularly if the growth rate converges slowly. (C) 2004 Elsevier B.V. All rights reserved.

Geogenic sources and sinks of trace metals in the Larsemann Hills, East Antarctica: Natural processes and human impact

To evaluate the extent of human impact on a pristine Antarctic environment, natural baseline levels of trace metals have been established in the basement rocks of the Larsemann Hills, East Antarctica. From a mineralogical and geochemical point of view the Larsemann Hills basement is relatively homogeneous, and contains high levels of Pb, Th and U. These may become soluble during the relatively mild Antarctic summer and be transported to lake waters by surface and subsurface melt water. Melt waters may also be locally enriched in V, Cr, Co, Ni, Zn and Sri derived from weathering of metabasite pods. With a few notable exceptions, the trace metal concentrations measured in the Larsemann Hills lake waters can be entirely accounted for by natural processes such as sea spray and surface melt water input. Thus, the amount of trace metals released by weathering of basement lithologies and dispersed into the Larsemann Hills environment, and presumably in similar Antarctic environments, is, in general, not negligible, and may locally be substantial. The Larsemann Hills sediments are coarse-grained and contain minute amounts of clay-size particles, although human activities have contributed to the generation of fine-grained material at the most impacted sites. Irrespective of their origin, these small amounts of fine-grained clastic sediments have a relatively small surface area and charge, and are not as effective metal sinks as the abundant, thick cyanobacterial algal mats that cover the lake floors. Thus, the concentration of trace metals in the Larsemann Hills lake waters is regulated by biological activity and thawing-freezing cycles, rather than by the type and amount of clastic sediment supply. (c) 2005 Elsevier Ltd. All rights reserved.