Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Information systems effectiveness: research designs for causal inference

Abstract. This paper examines the capacity of the research designs of 37 empirical studies of information systems (IS) effectiveness to provide a basis for the development of theories about behaviour related to IS effectiveness. The power of each study to support causal inference was evaluated in terms of (a) its handling of the time dimension, (b) its ability to weigh differences and (c) its resistance to internal validity threats that pose alternative explanations for its reported findings. Of the reviewed studies, 29.7% could account for the time dimension, 32.4% employed a comparison group and 16.2% were not susceptible to any internal validity threats. Only 13.5% of the studies combined an accounting for the time dimension with the use of a comparison group. Of these, however, only 5.4% were also invulnerable to internal validity threats. The research designs of nearly 95% of these published studies were deficient in supporting causal inference. In those studies, suggestions that one variable was causally related to another variable could not be substantiated. Encouragement for the future capacity of IS effectiveness research to support causal inference was found in a trend towards the use of quasiexperimental designs. Recommendations are made regarding ways to increase the inferential capacity of research designs employed in the study of IS effectiveness.     

A practical minimum distance method for syntax error handling

We present a method for recovering from syntax errors encountered during parsing. The method provides a form of minimum distance repair, has linear time complexity, and is completely automatic. A formal method is presented for evaluating the performance of error recovery methods, based on global minimum-distance error correction. The minimum-distance error recovery method achieves a theoretically best performance on 80% of Pascal programs in the weighted Ripley-Druseikis collection. Comparisons of performance with other error recovery methods are given.     

A general and flexible method of problem definition in structural optimization systems

This paper describes the implementation of a general and flexible method of formulating problems of mathematical programming in structural optimization systems. The method enables the formulation and solution of problems involving scalar, integral, min/max, max/min and possibly non-differentiable user defined functions in any conceivable mix. The mathematical formulation is based on the bound formulation, and the implementation specific details involve a parser capable of interpreting and performing symbolic differentiation of the user defined functions.     

Synthetic approach to optimal filtering

As opposed to the analytic approach used in the modern theory of optimal filtering, a synthetic approach is presented. The signal/sensor data, which are generated by either computer simulation or actual experiments, are synthesized into a filter by training a recurrent multilayer perceptron (RMLP) with at least one hidden layer of fully or partially interconnected neurons and with or without output feedbacks. The RMLP, after adequate training, is a recursive filter optimal for the given structure, with the lagged feedbacks carrying the optimal conditional statistics at each time point. Above all, it converges to the minimum variance filter as the number of hidden neurons increases. We call such an RMLP a neural filter. Simulation results show that the neural filters with only a few hidden neurons consistently outperform the extended Kalman filter and even the iterated extended Kalman filter for the simple nonlinear signal/sensor systems considered.     

Ends,Means and Innovation Management

The management of innovation inevitably implies the management of uncertainty. Research and practise clearly indicate that judgements about the size and the nature of this are often inaccurate. This can result in poor performance against expectations and in some cases in complete failure. In this paper it is argued that prior analysis of the type of uncertainty can help to improve the success rate and/or reduce the time to completion. Early signs that discontinuation, or a significant change in direction, might be called for are also highlighted by this analysis.     

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

An inhibitor of DNA topoisomerase I from Xenopus laevis ovaries

A novel, heat-resistant and Pronase-sensitive, inhibitor of eukaryotic DNA topoisomerase I has been purified from Xenopus laevis ovaries. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the most purified fraction revealed three bands with apparent molecular masses of 25, 28.5, and 33.5 kDa. The 25- and 33.5-kDa peptides recovered from an SDS-PAGE gel inhibited X. laevis DNA topoisomerase I. The purified inhibitor was specific to DNA topoisomerase I and did not inhibit other DNA enzymes tested. The inhibitor blocked the catalytic activity of DNA topoisomerase I by interacting with the enzyme, rather than by competing for binding sites on substrate DNA. Binding of DNA topoisomerase I to substrate DNA was blocked by the inhibitor, as was the cleavage reaction catalyzed by DNA topoisomerase I. Inhibition of DNA topoisomerase I was relieved by divalent cations Ca2+, Mg2+, or Mn2+.