Letter from Thomas Mason to Dr GF Story, Hobart 1849

A letter from Thomas Mason to Dr GF Story, Hobart 1849. Mason had requested JB (?) Mather to 'ship the skins', and had forwarded information to Story about this trade. Mason comments on mutual friends, such as William Galway, whose daughter had married, and Thomas Turner, who had died. From Cotton Family Papers C7/16

Protein dynamics with off-lattice Monte Carlo moves

A Monte Carlo method for dynamics simulation of all-atom protein models is introduced, to reach long times not accessible to conventional molecular dynamics. The considered degrees of freedom are the dihedrals at C$_\alpha$-atoms. Two Monte Carlo moves are used: single rotations about torsion axes, and cooperative rotations in windows of amide planes, changing the conformation globally and locally, respectively. For local moves Jacobians are used to obtain an unbiased distribution of dihedrals. A molecular dynamics energy function adapted to the protein model is employed. A polypeptide is folded into native-like structures by local but not by global moves.Comment: 10 pages, 4 Postscript figures, uses epsf.sty and a4.sty; scheduled tentatively for Phys.Rev.E issue of 1 March 199

Remedial action planning for Trench 1

The accelerated action to remove the depleted uranium chips and associated soils and wastes from Trench 1 at the Rocky Flats Environmental Technology Site (RFETS) will begin in June 1998. To ensure that the remedial action is conducted safely, a rigorous and disciplined planning process was followed that incorporates the principles of Integrated Safety Management and Enhanced Work Planning. Critical to the success of the planning was early involvement of project staff (salaried and hourly) and associated technical support groups and disciplines. Feedback was and will continue to be solicited, and lessons learned incorporated to ensure the safe remediation of this site

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98–1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03–1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00–2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16–2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07–1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted

Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial.

Transarterial chemoembolisation (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma, while the multikinase inhibitor sorafenib improves survival in patients with advanced disease. We aimed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo.This article is freely available via Open Access. Click on Additional Link above to access the full-text via the publisher's site.Publishe