A scientist's view of bioengineering.

So, to summarize: my themes in this lecture have been: 1. Bioengineering is a many-splendoured thing. 2. There are few differences in principle between scientists and engineers, and they need to work together and respect one another's special contribution. 3. The Department of Health has done much to enhance your career structure and prospects recently; now you have to help us to polish your image even further. 4. There is urgent need for collaboration amongst all parties if we are to counter some potentially deleterious effects of the recent NHS reforms on the work of clinical scientists and engineers. Finally, I wanted to thank you for admitting me, just a little way, into the magical world of biological engineering. Life has become infinitely more exciting since you did so, and I owe you all a considerable debt of gratitude.

Microcomputer software to facilitate costing in pathology laboratories.

A software program is described which will enable laboratory managers to calculate, for their laboratory over a 12 month period, the cost of each test or investigation and of components of that cost. These comprise the costs of direct labour, consumables, equipment maintenance and depreciation; allocated costs of intermediate operations--for example, specimen procurement, reception, and data processing; and apportioned indirect costs such as senior staff time as well as external overheads such as telephone charges, rent, and rates. Total annual expenditure on each type of test is also calculated. The principles on which the program is based are discussed. Considered in particular, are the problems of apportioning indirect costs (which are considerable in clinical laboratory work) over different test costs, and the merits of different ways of estimating the amount or fraction of staff members' time spent on each kind of test. The computer program is Crown copyright but is available under licence from one of us (JAS).

Strategies to modify the test-requesting patterns of clinicians.

Studies of the effectiveness of various strategies for influencing clinicians' test-requesting behaviour are reviewed. Numerical rationing, although crude, effectively reduces unnecessary repeat testing without detriment to patient outcome. Educational programmes involving peer review show pronounced but short-lived effects. Simple feedback of information about numbers of tests requested and their costs is surprisingly ineffectual. Direct financial incentives, in a private health care system, also failed. Clinical budgeting, of benefit in experimental trials, has yet to be widely tested, and the savings on reducing laboratory requesting may not be large enough to be attractive to clinicians. Agreed requesting policies in various specialties and clinical circumstances, endorsed by senior clinicians and prestigious professional bodies, seems a promising approach to more appropriate test requesting; further objective studies of their long-term effects are needed. Redesign of request forms into a problem-orientated format may be the simplest and most effective contribution by the laboratory; this strategy deserves further critical appraisal.

Combined external quality assessment of cytology and histology opinions: a pilot scheme for a cluster of five laboratories.

A cluster of five self selected cytodiagnostic laboratories circulated 70 cervical/vaginal smears and 50 sputum smears in a series of five week cycles. Histological sections related to the abnormal smears were also circulated. Proportions of agreement and disagreement were analysed for cervical and sputum smear reports against the original report (and by implication against the consensus); corresponding calculations were made for the histological reports. Cytological and histological correlation was also examined. Agreement for major categories (benign, intraepithelial neoplasia, malignant) was 87% for cervical cytology and 83% for sputum. When the effect of potential random agreement was compensated for by the use of kappa statistics the values of kappa were +0.79 and +0.65, respectively. The corresponding kappa values for gynaecological and respiratory tract histology were +0.78 and +0.82, respectively. Agreement on finer degrees of abnormality was, predictably, less good. Problems arising in this pilot scheme are discussed and suggestions for a simplified scheme are made.

Stability of four steroids in lyophilised human serum.

The stability of a preparation of lyophilised serum and its suitability for use as a reference material for routine assays of cortisol, oestradiol, and progesterone have been studied in four laboratories with a variety of assay systems. Cortisol and oestradiol were also measured by gas chromatography-mass spectrometry. The lyophilised serum was suitable for use in all routine and reference assay methods examined, with between-method variability no greater than that for frozen serum pools. The concentrations of cortisol, oestradiol, and progesterone were predicted by accelerated degradation studies to decline by 0.01% per annum if the preparations were to be stored at --20 degrees C. The testosterone content of the preparation, determined in one laboratory, provided no evidence for degradation. The preparation can be shipped for use at ambient temperature without deleterious effect.

Benefits of costing in the clinical laboratory.

This paper urges the benefits of applying more widely a method for pathology laboratory costing originally devised for a clinical chemistry department, and illustrates these with examples drawn from costing studies in three clinical laboratories. Heads of pathology departments, laboratory managers, administrators and clinicians require different kinds of costing information, each of which can be obtained by the costing procedure outlined. The method also yields valuable and sometimes surprising insights into the workings of a pathology service. Cost comparisons between different laboratories can now become more informative. Flaws in the concept of the "cost per test" are discussed and the value of this concept is questioned; for most purposes the cost per request has greater application.

External quality assessment of clinical laboratories in the United Kingdom.

A review is given of the National External Quality Assessment Schemes (NEQASs) in various pathology disciplines in the United Kingdom, with a discussion of the relative roles of the DHSS, individual laboratory scientists, and the relevant professional bodies. Principles of operation and scientific problems in the design of NEQASs in different disciplines are described and contrasted, and some comparisons with the experience in other European countries and the USA are drawn.

Maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects.

Nineteen centres collaborated in a study to determine the efficiency of maternal serum-alpha-fetoprotein (A.F.P.) measurement as a method of screening for neural-tube defects (N.T.D.S.) between 10 and 24 weeks of pregnancy. Data were collected on 18 684 singleton pregnancies and 163 twin pregnancies without fetal N.T.D.s, and on 301 singleton pregnancies with fetal N.T.D.s (146 with anencephaly, 142 with spina bifida, and 13 with encephalocele). The best time for detecting open spina bifida by measuring maternal serum-A.F.P. is at 16-18 weeks of pregnancy. In clinical practice, serum-A.F.P. cut-off levels expressed as multiples of the normal median may be more convenient to use than percentiles because they are easier to derive and more stable. Also, the proportion of affected pregnancies with serum-A.F.P. levels exceeding a given multiple of the median is unlikely to vary significantly from centre to centre or over time. In contrast, the proportion of unaffected pregnancies with A.F.P. levels exceeding a given multiple of the normal median will vary depending on the precision with which serum-A.F.P. and gestation are measured. At 16-18 weeks of pregnancy 88% of cases of anencephaly, 79% of cases of open spina bifida, and 3% of unaffected singleton pregnancies had A.F.P. levels equal to or greater than 2-5 times the median for unaffected singleton pregnancies. At this gestation age the numbers of unaffected pregnancies with A.F.P. levels above 2-5 times the normal median can be reduced by about a third if women with borderline A.F.P. levels are retested, although this would not greatly change the detection-rate of affected pregnancies. In the United Kingdom as a whole, women with serum-A.F.P. levels above 2-5 times the normal median at 16-18 weeks of gestation will have an approximately 1-in-20 chance of having a fetus with open spina bifida; the risk of having any N.T.D. will be approximately 1 in 10. The results of this study indicate that screening pregnant women by measuring the concentration of A.F.P. in their serum is an effective method of selecting women for ultrasonography and amniocentesis so that N.T.D.s can be diagnosed in utero.

Enlargement of taurocholate micelles by added cholesterol and monoolein: self-diffusion measurements.

The effect of solubilized cholesterol and 1-monoolein on the size of micellar aggregates of sodium taurocholate (3alpha,7alpha,12alpha-trihydroxy-5-cholanoyl taurine) has been determined in vitro. Measurements of the self-diffusion coefficient of sodium taurocholate (0.15 m in Na(+)) at 37 degrees C and pH 7.4 led to the conclusion that at concentrations above the critical micelle concentration (6.7 mm) the solutions contain, besides monomeric ions, a single micellar species containing five taurocholate ions. In the presence of cholesterol, much larger micelles are formed, apparently containing one molecule of cholesterol and 25 of taurocholate. These mixed micelles coexist with small micelles of pure taurocholate as well as the taurocholate monomers. The addition of 1-monoolein increases the solubility of cholesterol in the taurocholate solution, but not by reducing the size of the micelle into which the cholesterol will fit: three-component micelles (monoolein-taurocholate-cholesterol) are, if their diffusion coefficients are any guide, still larger than taurocholate-cholesterol micelles. The molar ratio of cholesterol to taurocholate is higher in these solutions than in the absence of monoolein. Comparison with work by other authors on taurodeoxy-cholate-cholesterol micelles suggests that more than 25 molecules of either dihydroxy or trihydroxy bile salts are needed to transport each molecule of cholesterol through an aqueous solution in the absence of other amphipathic molecules.

Sounder thinking through clearer writing. A graduate course on scientific writing can, if appropriately designed, strengthen scientific thinking.

Bad scientific writing involves more than stylistic inelegance: it is often the outward and visible form of an inward confusion of thought. The scientific literature at its present standard distorts rather than forms the graduate student's view of scientific knowledge and thought, and corrupts his ability to write, to read, and to think. Strong educational measures are needed to effect reform. I advocate a course on scientific writing as an essential feature in every scientist's training. Such a course delves deep into the philosophy and method of science if it deals with logic, precision, and clarity; on how these qualities can be achieved in writing; and on how such achievement strengthens the corresponding faculties in thinking.