Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication

We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.     

The MITRE E3 family of models structure and results

A family of energy/economic/environmental (E³) models is presented as a mechanism for analysing national policy issues. The family consists of discrete models which are designed to be run in an integrated manner. The outputs of certain models provide the inputs to the next. This structure allows the analyst to readily incorporate an understanding of regional factors such as local energy prices, concerns over air quality, water availability, or attitudes towards construction of new energy facilities, into national assessments of energy policies. This paper reviews the analytic framework within which energy policy issues are currently addressed. The initial family of E³ models is described with the emphasis on the data linkages and feedback which are provided when these models are run sequentially. The ongoing MITRE research programme with the E³ family of models is presented and plans and opportunities for future work are outlined.     

Polymorphism of silica

A study of the stability relations of pure silica phases is described. It is shown that although cristobalite can be produced from pure quartz by heating it is not possible to produce tridymite in this fashion; a flux or mineralizer is required for tridymite formation and even in this case cristobalite is produced before any tridymite is observed. Thus it is concluded that the stability relations for the silica minerals proposed by Fenner are incorrect and that tridymite is not a stable phase in the pure silica system. This revised version was published online in November 2006 with corrections to the Cover Date.     

Advanced intelligent networks: now a reality

This paper looks first at the background to the development of intelligent networking concepts and then tracks this development to the advanced intelligent networks (AINs) of today. The network architecture and basic nodal functions are explained, and a brief review given of the essential intelligent network building blocks, namely the IN (intelligent network) call model and the enhanced CCITT No.7 signalling system. Typical intelligent network services are examined and the tutorial finishes with a review of the latest IN standards     

The failure of an F/A-18 trailing edge flap hinge

During a flight over sea, the right-hand trailing-edge flap (TEF) from an RAAF F/A-18 separated. Although the flap was not recovered, the mode of failure suggested that the outboard hinge lug was first to fail. A fleet-wide inspection of the TEF outer hinge lugs disclosed two other cracked hinge lugs. Examination of these cracks revealed that they had propagated as the result of a combination of corrosion and fatigue, in that the corrosive environment appeared to have accelerated the fatigue crack growth rate. Laboratory experiments indicated that, in a salt solution, the 7050 aluminium alloy from which the lugs were manufactured is susceptible to corrosion fatigue and that the observed cracking matched that on the cracked lugs: corrosion fatigue was therefore suspected to have been a contributing factor in the unexpected failure. Quantitative fractography on the fatigue cracks, combined with several assumptions and deductions, including information about the failure size of the crack gained from witness marks found on the monoball bearing of the failed TEF, led to an estimate of the fatigue crack growth rate. This crack growth rate and the short service life clearly indicated the limitations of the then-current non-destructive inspection (NDI) technique, and a more sensitive inspection method was developed to assist in the maintenance of adequate RAAF flying hours between inspections. This failure investigation provided an excellent example of how fractography, laboratory experiments and NDI can be combined to determine a possible cause of failure and to establish remedial measures for the fleet.     

Evolution of the serum amyloid A (SAA) protein superfamily

The serum amyloid A (SAA) superfamily comprises a number of genes and proteins characterized from a range of mammalian species. The majority of members described to date are dramatically induced during the acute-phase response, suggesting an important short-term beneficial role in the response to tissue injury and inflammation. However, important disease associations have also been proposed for certain SAAs during chronic inflammation. The nomenclature of many of the superfamily members has been the result of comparisons with previously reported sequences implying disease association and/or functional relatedness between such members. The evolutionary relationships of the SAA superfamily members have been investigated by comparisons at both the amino acid and the nucleotide level. The results indicate that all members of the superfamily within a species have been undergoing concerted evolution. This has important implications in ascribing functions and disease associations to individual SAA superfamily members and indicates that designations should not be based on the extent of amino acid identity alone but should be made only following direct experimental observation of the proteins themselves.     

Sheep pulmonary adenomatosis: a unique model of retrovirus-associated lung cancer

Sheep pulmonary adenomatosis (SPA) is a contagious bronchiolo-alveolar carcinoma of sheep associated with an exogenous type D/B retrovirus known as jaagsiekte sheep retrovirus (JSRV). SPA represents a unique model for lung cancer, and studies on its aetiopathogenesis can provide further insight into the mechanisms of epithelial neoplasms.     

Livsic theorems,maximizing measures and the stable norm

In this paper we consider two results motivated by Livsic's well-known theorem that, for a hyperbolic system, a Hölder continuous function is determined, up to a coboundary, by its values around closed orbits. The first result relates to negative values around orbits and the second result to values for finitely many orbits. We also present some new results on maximizing measures and the boundary of the unit ball in the stable norm for a surface.