Adverse drug reactions from psychotropic medicines in the paediatric population: analysis of reports to the Danish Medicines Agency over a decade

<p>Abstract</p> <p>Background</p> <p>The prescribing of psychotropic medicines for the paediatric population is rapidly increasing. In attempts to curb the use of psychotropic medicine in the paediatric population, regulatory authorities have issued various warnings about risks associated with use of these products in childhood. Little evidence has been reported about the adverse drug reactions (ADRs) of these medicines in practice. As spontaneous reports are the main source for information about previously unknown ADRs, we analysed data submitted to a national ADR database. The objective was to characterise ADRs reported for psychotropic medicines in the Danish paediatric population over a decade.</p> <p>Findings</p> <p>All spontaneous ADR reports from 1998 to 2007 for children from birth to 17 years of age were included. The unit of analysis was one ADR. We analysed the distribution of ADRs per year, seriousness, age and gender of the child, suspected medicine and type of reported ADR. A total of 429 ADRs were reported for psychotropic medicines and 56% of these were classified as serious. Almost 20% of psychotropic ADRs were reported for children from birth up to 2 years of age and one half of ADRs were reported in adolescents, especially for antidepressants and psychostimulants. Approximately 60% of ADRs were reported for boys. Forty percent of all ADRs were from the category 'nervous and psychiatric disorders'. All but one ADR reported for children below two years were serious and two of these were fatal. A number of serious ADRs reported in children from birth up to 2 years of age were presumably caused by mothers' use of psychotropic medicines during pregnancy.</p> <p>Conclusion</p> <p>The high number of serious ADRs reported for psychotropic medicines in the paediatric population should be a concern for health care professionals and physicians. Considering the higher number of birth defects being reported greater care has to be given while prescribing these drugs for pregnant women.</p

The St. Lawrence polynya and the Bering shelf circulation : new observations and a model comparison

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): C09023, doi:10.1029/2005JC003268.Using 14 year-long instrumented moorings deployed south of St. Lawrence Island, along with oceanographic drifters, we investigate the circulation over the central Bering shelf and the role of polynyas in forming and disseminating saline waters over the shelf. We focus also on evaluating the Gawarkiewicz and Chapman [1995] model of eddy production within coastal polynyas. Principal results include: 1) The northern central shelf near-surface waters exhibit westward flow carrying low-salinity waters from the Alaskan coast in fall and early winter, with consequences for water mass formation and biological production. 2) Within the St. Lawrence polynya, the freshening effect of winter advection is about half as large as the salting effect of surface brine flux resulting from freezing. 3) Brine production over the Bering shelf occurs primarily offshore, rather than within coastal polynyas, even though ice production per unit area is much larger within the polynyas. 4) We find little evidence for the geostrophic flow adjustment predicted by recent polynya models. 5) In contrast to the theoretical prediction that dense water from the polynya is carried offshore by eddies, we find negligible cross-shelf eddy density fluxes within and surrounding the polynya and very low levels of eddy energy that decreased from fall to winter, even though dense water accumulated within the polynya and large cross-shore density gradients developed. 6) It is possible that dense polynya water was advected downstream of our array before appreciable eddy fluxes materialized.This work was supported by National Science Foundation grant OCE9730697 to the University of Alaska and grant OCE9730823 to the University of Washington. S. M. acknowledges the support of the National Science Foundation under OCE9811097 and of NASA under grant NNG04GM69G. The University of Hamburg contributions were funded by the Bundesminister für Bildung und Wissenschaft. Funding for the drifter deployment was made possible by the North Pacific Research Board, grant NPMRI T2130. Manuscript preparation was additionally supported by Office of Naval Research grants N00014-99-1-0345 and N00014-02-1-0305 to the University of Washington

Eddy transport of organic carbon and nutrients from the Chukchi Shelf : impact on the upper halocline of the western Arctic Ocean

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): C05011, doi:10.1029/2006JC003899.In September 2004 a detailed physical and chemical survey was conducted on an anticyclonic, cold-core eddy located seaward of the Chukchi Shelf in the western Arctic Ocean. The eddy had a diameter of ∼16 km and was centered at a depth of ∼160 m between the 1000 and 1500 m isobaths over the continental slope. The water in the core of the eddy (total volume of 25 km3) was of Pacific origin, and contained elevated concentrations of nutrients, organic carbon, and suspended particles. The feature, which likely formed from the boundary current along the edge of the Chukchi Shelf, provides a mechanism for transport of carbon, oxygen, and nutrients directly into the upper halocline of the Canada Basin. Nutrient concentrations in the eddy core were elevated compared to waters of similar density in the deep Canada Basin: silicate (+20 μmol L−1), nitrate (+5 μmol L−1), and phosphate (+0.4 μmol L−1). Organic carbon in the eddy core was also elevated: POC (+3.8 μmol L−1) and DOC (+11 μmol L−1). From these observations, the eddy contained 1.25 × 109 moles Si, 4.5 × 108 moles NO3 −, 5.5 × 107 moles PO3 −, 1.2 × 108 moles POC, and 1.9 × 109 moles DOC, all available for transport to the interior of the Canada Basin. This suggests that such eddies likely play a significant role in maintaining the nutrient maxima observed in the upper halocline. Assuming that shelf-to-basin eddy transport is the dominant renewal mechanism for waters of the upper halocline, remineralization of the excess organic carbon transported into the interior would consume 6.70 × 1010 moles of O2, or one half the total oxygen consumption anticipated arising from all export processes impacting the upper halocline.This work was supported by the National Science Foundation, and office of Naval Research; DH OPP-0124900, NB OPP-0124868, DK OPP 0124872, RP N00014-02-1-0317

In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model

OBJECTIVE: Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. STUDY DESIGN: WT and Glut4(+/-) (G4(+/-)) offspring of WT mothers that were exposed either to a control or an HFD in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5-week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP-on-chip) was used to detect genome-wide changes of histone modifications with HFD exposure. RESULTS: We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4(+/-) fetal and 5-week offspring. Pathway analysis of our ChIP-on-chip data revealed differential H3K14ac and H3K9me3 enrichment along pathways that regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra, and Rora. CONCLUSION: We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4(+/-) offspring, some of which persist up to 5 weeks of age

Isometric group actions on Banach spaces and representations vanishing at infinity

Our main result is that the simple Lie group $G=Sp(n,1)$ acts properly isometrically on $L^p(G)$ if $p>4n+2$. To prove this, we introduce property ({\BP}_0^V), for $V$ be a Banach space: a locally compact group $G$ has property ({\BP}_0^V) if every affine isometric action of $G$ on $V$, such that the linear part is a $C_0$-representation of $G$, either has a fixed point or is metrically proper. We prove that solvable groups, connected Lie groups, and linear algebraic groups over a local field of characteristic zero, have property ({\BP}_0^V). As a consequence for unitary representations, we characterize those groups in the latter classes for which the first cohomology with respect to the left regular representation on $L^2(G)$ is non-zero; and we characterize uniform lattices in those groups for which the first $L^2$-Betti number is non-zero.Comment: 28 page

Long-term trends of temperature, salinity, density and transient tracers in the Central Greenland Sea

We present long-term observations of temperature, salinity, tritium/3He, chlorofluorocarbon-11 (CFC 11), and chlorofluorocarbon-12 (CFC 12) for the central Greenland Gyre. The time series span the periods between 1952 and 1994 (temperature), 1981 and 1994 (salinity), 1972 and 1994 (tritium/3He), and 1982 and 1994 (CFCs). The correlation between hydrographic and transient tracer data indicates that low temperatures in the deep water in the early 1950s and between 1960 and 1980 reflect periods of higher deep water formation rates whereas periods of increasing temperatures in the late 1950s and between 1980 and 1994 are related to low deep water formation rates. However, the transient tracer observations obtained in the 1980s and early 1990s indicate that even during periods of low deep water formation, some water from the upper water column contributed to deep water formation between 1980 and 1994. In 1994, the deep water reached temperatures and salinities of −1.149 °C and 34.899, respectively, and no longer fits most of the classical definitions of Greenland Sea Deep Water (−1.29°C< Θ < −1.0°C, 34.88<S<34.90). The temperature increase in the water column between 200 and 2000 m depth between 1980 and 1994 corresponds to an average heating rate of about 5 Wm−2 over this period, resulting in a decrease in density. The 13-year warming could be balanced by intensive cooling in two winters. The surface salinity steadily increased from 34.50 in 1991 to 34.85 in 1994