Thirty thousand miles in "The Wanderer" : extracts from the log kept at various times by John Boit and Sam P. Blagden, Jr /

Mode of access: Internet.

Sam Jones' gospel sermons /

Mode of access: Internet.

Phase I study of GSK461364, a specific and competitive Polo-like Kinase 1 (PLK1) inhibitor in patients with advanced solid malignancies.

Purpose: GSK461364 is an ATP-competitive inhibitor of polo-like kinase 1 (Plk1). A phase I study of two schedules of intravenous GSK461364 was conducted. Experimental Design: GSK461364 was administered in escalating doses to patients with solid malignancies by two schedules, either on days 1, 8, and 15 of 28-day cycles (schedule A) or on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (schedule B). Assessments included pharmacokinetic and pharmacodynamic profiles, as well as marker expression studies in pretreatment tumor biopsies. Results: Forty patients received GSK461364: 23 patients in schedule A and 17 in schedule B. Dose-limiting toxicities (DLT) in schedule A at 300 mg (2 of 7 patients) and 225 mg (1 of 8 patients) cohorts included grade 4 neutropenia and/or grade 3–4 thrombocytopenia. In schedule B, DLTs of grade 4 pulmonary emboli and grade 4 neutropenia occurred at 7 or more days at 100 mg dose level. Venous thrombotic emboli (VTE) and myelosuppression were the most common grade 3–4, drug-related events. Pharmacokinetic data indicated that AUC (area under the curve) and C max (maximum concentration) were proportional across doses, with a half-life of 9 to 13 hours. Pharmacodynamic studies in circulating tumor cells revealed an increase in phosphorylated histone H3 (pHH3) following drug administration. A best response of prolonged stable disease of more than 16 weeks occurred in 6 (15%) patients, including 4 esophageal cancer patients. Those with prolonged stable disease had greater expression of Ki-67, pHH3, and Plk1 in archived tumor biopsies. Conclusions: The final recommended phase II dose for GSK461364 was 225 mg administered intravenously in schedule A. Because of the high incidence (20%) of VTE, for further clinical evaluation, GSK461364 should involve coadministration of prophylactic anticoagulation.

Sermons and sayings /

Mode of access: Internet.

Hot shots : or, Sermons and sayings /

Mode of access: Internet.

Namyang Hong Ssi sebo.

Imprint date from preface: Sungjŏng Kapsinhu Sam P��ngsin, sŏ.

Drivers of atmospheric methane uptake by montane forest soils in the southern Peruvian Andes

Acknowledgements. This study is a product of the Andes Biodiversity and Ecosystem Research Group consortium (http://www.andesconservation.org/). The authors would like to acknowledge the agencies that funded this research; the UK Natural Environment Research Council (NERC; joint grant references NE/G018278/1, NE/H006583, NE/H007849 and NE/H006753) and the Norwegian Agency for Development Cooperation (Norad; via a sub-contract to Yit Arn Teh managed by the Amazon Conservation Association). Patrick Meir was also supported by an Australian Research Council Fellowship (FT110100457). Javier Eduardo Silva Espejo, Walter Huaraca Huasco and the ABIDA NGO provided critical fieldwork and logistical support. Angus Calder, Michael Mcgibbon, Vicky Munro and Nick Morley provided invaluable laboratory support. Thanks to Adrian Tejedor and the Amazon Conservation Association (http://www.amazonconservation.org/), who provided assistance with access and plot selection at Hacienda Villa Carmen. This publication is a contribution from the Scottish Alliance for Geoscience, Environment and Society (http://www.sages.ac.uk). Edited by: E. Veldkamp