An evaluation of self-administering arithmetic enrichment activities for grades 4, 5, and 6

Thesis (Ed.M.)--Boston Universit

Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative Colitis

Michael McGuckin and colleagues identify two mutations that cause aberrant mucin oligomerization in mice. The resulting phenotype, including endoplasmic reticulum stress, resembles clinical and pathologic features of human ulcerative colitis

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Effect of β-Carotene Supplementation on the Pharmacokinetics of Nelfinavir and Its Active Metabolite M8 in HIV-1-infected Patients

β-Carotene supplements are often taken by individuals living with HIV-1. Contradictory results from in vitro studies suggest that β-carotene may inhibit or induce cytochrome P450 enzymes and transporters. The study objective was to investigate the effect of β-carotene on the steady-state pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1 infected individuals. Twelve hour nelfinavir pharmacokinetic analysis was conducted at baseline and after 28 days of β-carotene supplementation (25,000 IU twice daily). Nelfinavir and M8 concentrations were measured with validated assays. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Geometric mean ratios comparing day 28 to day 1 area under the plasma concentration-time curve (AUC0–12 h), maximum (Cmax) and minimum (Cmin) concentrations of nelfinavir and M8 are presented with 90% confidence intervals. Eleven subjects completed the study and were included in the analysis. There were no significant differences in nelfinavir AUC0–12 h and Cmin (−10%, +4%) after β-carotene supplementation. The M8 Cmin was increased by 31% while the M8 AUC0–12 h and Cmax were unchanged. During the 28 day period, mean CD4+ % and CD4+:CD8+ ratio increased significantly (p < 0.01). β-carotene supplementation increased serum carotene levels but did not cause any clinically significant difference in the nelfinavir and M8 exposure

La pharmacocinétique clinique des antirétroviraux : de la théorie à la pratique

Résumé Objectif : Décrire le programme de pharmacocinétique clinique des antirétroviraux de Nijmegen, Pays-Bas, tel qu’observé lors de la bourse GlaxoSmithKline 2004. Mise en contexte : Pendant six semaines, j’ai effectué un stage au Centre médical Radboud (Nijmegen, Pays-Bas) afin d’approfondir mes connaissances et mon expérience clinique sur la pharmacocinétique clinique des antirétroviraux. Près de 250 concentrations plasmatiques d’inhibiteurs de la protéase et d’inhibiteurs non nucléosidiques de la transcriptase inverse ont été analysées et interprétées pendant mon séjour. Des rapports d’avis pharmacologique ont été rédigés pour les médecins traitants pour chaque concentration plasmatique. Les prélèvements sanguins provenant de centres hospitaliers à travers les Pays-Bas ont été analysés avec une méthode analytique précise et fiable utilisant la chromatographie liquide à haute performance avec détection par rayons ultraviolets. Les concentrations plasmatiques ont été interprétées à l’aide de rapport de concentration et de quotient inhibiteur génotypique pour les inhibiteurs de la protéase et à l’aide de concentrations minimales et maximales visées pour les inhibiteurs non nucléosiques de la transcriptase inverse. Conclusion : Le programme de pharmacocinétique clinique des antirétroviraux à ce centre est hautement efficace, mais il pourrait bénéficier d’une collecte de données plus exhaustive afin d’individualiser davantage les interprétations et les recommandations d’ajustements posologiques. Abstract Objective : Describe the antiretroviral therapeutic drug monitoring program in Nijmegen, the Netherlands, as observed during the 2004 GlaxoSmithKline scholarship. Context : A six week rotation was completed at the Radboud Medical Centre (Nijmegen, the Netherlands) to expand my antiretroviral therapeutic drug monitoring knowledge and clinical experience. Close to 250 plasma concentrations of protease inhibitors and non-nucleoside reverse transcriptase inhibitors were analyzed and interpreted during this period. Written reports with pharmacological advice were sent to the treating physicians for each plasma concentration. Blood samples originating from various parts of the Netherlands were analyzed with an accurate and reliable analytical method using high-performance liquid chromatography with ultraviolet detection. The protease inhibitors concentrations were interpreted using concentration ratios and genotypic inhibitory quotients, while non-nucleoside reverse transcriptase inhibitors concentrations were interpreted with targeted minimal and maximal concentrations. Conclusion: The antiretroviral therapeutic drug monitoring program at this centre is highly efficient, but could benefit from more extensive data collection in order to further individualize the interpretations and dose adjustment recommendations. Keywords: therapeutic drug monitoring, antiretroviral, concentration ratio, genotypic inhibitory quotient

PHARMACY PRACTICE Antiretroviral Therapeutic Drug Monitoring in Canada: Current Status and Recommendations for Clinical Practice

Therapeutic drug monitoring (TDM) is a strategy whereby the plasma concentration of one or more drugs is measured and drug doses are adjusted accordingly to achieve concentrations within an acceptable therapeutic range. Th