High resolution measurements of density structures in the Jovian plasma sheet

A recent effort to digitize the plasma density by using the low frequency cutoff of trapped continuum radiation in the vicinity of the Jovian plasma sheet has revealed the existence of sharply defined density structures in the plasma sheet. These structures typically have a plasma density which is relatively constant but of order 50 percent greater or less than in the surrounding plasma. At the boundaries of these structures, the transitions from low to high density occur on time scales of about ten seconds, which correspond to spatial dimensions on the order of a few ion Larmor radii. The structures themselves last for intervals from less than a minute to more than five minutes, corresponding to size scales from a fraction of a Jovian radius to more than a Jovian radius, depending of the velocity of the structure relative to the spacecraft. In view of the importance of near corotation plasma flows, these structures are likely to be limited in both the longitudinal and radial dimensions and, therefore, could represent flux tubes with greatly varying plasma content. These observations are presented as among the first to directly address the theoretically proposed interchange instability

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Australian health care providers' views on opt-out HIV testing

Background: Opt-out HIV testing is a novel concept in Australia. In the opt-out approach, health care providers (HCPs) routinely test patients for HIV unless they explicitly decline or defer. Opt-out HIV testing is only performed with the patients' consent, but pre-test counselling is abbreviated. Australian national testing guidelines do not currently recommend opt-out HIV testing for the general population. Non-traditional approaches to HIV testing (such as opt-out) could identify HIV infections and facilitate earlier treatment, which is particularly important now that HIV is a chronic, manageable disease. Our aim was to explore HCPs' attitudes toward opt-out HIV testing in an Australian context, to further understanding of its acceptability and feasibility. Methods: In this qualitative study, we used purposeful sampling to recruit HCPs who were likely to have experience with HIV testing in Western Australia. We interviewed them using a semi-structured guide and used content analysis as per Graneheim to code the data. Codes were then merged into subcategories and finally themes that unified the underlying concepts. We refined these themes through discussion among the research team. Results: Twenty four HCPs participated. Eleven participants had a questioning attitude toward opt-out HIV testing, while eleven favoured the approach. The remaining two participants had more nuanced perspectives that incorporated some characteristics of the questioning and favouring attitudes. Participants' views about opt-out HIV testing largely fell into two contrasting themes: normalisation and routinisation versus exceptionalism; and a need for proof versus openness to new approaches. Conclusion: Most HCPs in this study had dichotomous attitudes toward opt-out HIV testing, reflecting contrasting analytical styles. While some HCPs viewed it favourably, with the perceived benefits outweighing the perceived costs, others preferred to have evidence of efficacy and cost-effectiveness

Desarrollo de una herramienta de análisis cuantitativo de movimiento en extremidades superiores

IP 1204-04-11879PONENCIA(S) EN CONGRESO: Calculation of optimal trajetorias forthe upperlimb / Carlos F. Rodriguez, Juan;C. Botero, J. Alfonso Pamanes. -- (2004 : Nov. 13-19 : Anaheim,California USA) Anaheim, California USA Nov.;13-19 : 2004

Desarrollo de una herramienta de análisis cuantitativo de movimiento en extremidades superiores

IP 1204-04-11879PONENCIA(S) EN CONGRESO: Calculation of optimal trajetorias forthe upperlimb / Carlos F. Rodriguez, Juan;C. Botero, J. Alfonso Pamanes. -- (2004 : Nov. 13-19 : Anaheim,California USA) Anaheim, California USA Nov.;13-19 : 2004

The ability of amine <i>N</i>-methyltransferases from rabbit liver to <i>N</i>-methylate azaheterocycles

Abstract The substrate specificity of two homogeneous amine N-methyltransferases from rabbit liver has been demonstrated to extend to the azaheterocycles pyridine, R-(+)-nicotine and S-(−)-nicotine. Both enzymes methylate R-(+)-nicotine at the pyridyl nitrogen to afford the N-methylnicotinium salt, whereas S-(−)-nicotine does not act as a substrate for either enzyme. Surprisingly, R-(+)-nicotine is methylated at either the pyridyl nitrogen, or the pyrrolidine nitrogen, to afford the two isomeric monomethylate nicotinium ions when an enzymic preparation containing both methyl transferase activities was used. Under similar conditions S-(−)-nicotine was methylated only at the pyridyl nitrogen. The production of charged metabolites in-vivo, from the large number of pyridine-compounds that are used as drugs, or are present in the environment, may be of toxicological significance, in view of the reported toxicities of several such quaternary ammonium compounds.</jats:p

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

Belinostat is a hydroxamate class HDAC inhibitor that has demonstrated activity in peripheral T-cell lymphoma and is undergoing clinical trials for non-hematologic malignancies. We studied the pharmacokinetics of belinostat in hepatocellular carcinoma patients to determine the main pathway of metabolism of belinostat. The pharmacokinetics of belinostat in liver cancer patients were characterized by rapid plasma clearance of belinostat with extensive metabolism with more than 4-fold greater relative systemic exposure of major metabolite, belinostat glucuronide than that of belinostat. There was significant interindividual variability of belinostat glucuronidation. The major pathway of metabolism involves UGT1A1-mediated glucuronidation and a good correlation has been identified between belinostat glucuronide formation and glucuronidation of known UGT1A1 substrates. In addition, liver microsomes harboring UGT1A1*28 alleles have lower glucuronidation activity for belinostat compared to those with wildtype UGT1A1. The main metabolic pathway of belinostat is through glucuronidation mediated primarily by UGT1A1, a highly polymorphic enzyme. The clinical significance of this finding remains to be determined.ClinicalTrials.gov NCT00321594</p