Sensitive and specific measurement of minimal residual disease in acute lymphoblastic leukemia.

A sensitive and specific quantitative real-time polymerase chain reaction method, involving three rounds of amplification with two allele-specific oligonucleotide primers directed against an rearrangement, was developed to quantify minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL). For a single sample containing 10 microg of good quality DNA, MRD was quantifiable down to approximately 10(-6), which is at least 1 log more sensitive than current methods. Nonspecific amplification was rarely observed. The standard deviation of laboratory estimations was 0.32 log units at moderate or high levels of MRD, but increased markedly as the level of MRD and the number of intact marker gene rearrangements in the sample fell. In 23 children with ALL studied after induction therapy, the mean MRD level was 1.6 x 10(-5) and levels ranged from 1.5 x 10(-2) to less than 10(-7). Comparisons with the conventional one-round quantitative polymerase chain reaction method on 29 samples from another 24 children who received treatment resulted in concordant results for 22 samples and discordant results for seven samples. The sensitivity and specificity of the method are due to the use of nested polymerase chain reaction, one segment-specific and two allele-specific oligonucleotide primers, and the use of a large amount of good quality DNA. This method may improve MRD-based decisions on treatment for ALL patients, and the principles should be applicable to DNA-based MRD measurements in other disorders.

Ethics in construction project briefing.

The research reported in this paper set out to investigate ethics in the initial stages of construction projects. Briefing is the first real contact stage between the commissioner (client/employer) of a project--at this stage a potential project--and those involved in project realization--the designers and, subsequently, the constructors. It is well known that early decisions are of greatest impact and so, the importance of the initial contacts, communications and consequent decisions are paramount. Different project participants are known to pursue individual objectives to varying degrees as well as possessing different perspectives and perceptions and operating/behaving in different ways. Hence, determination of the appropriate form, content etc. of a project is, inevitably, a matter of exercising value judgements and compromises and so, involves ethical considerations. A case study of a project through the briefing stage is reported and analysed, from initial contacts to scheme approval. It is apparent that a number of ethical concerns are manifest through the various actions of the major participants.