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Assumptions of the QALY procedure.

The Quality Adjusted Life Year (QALY) has been proposed as a useful index for those managing the provision of health care because it enables the decision-maker to compare the 'value' of different health care programmes and in a way which, potentially at least, reflects social preferences about the appropriate pattern of provision. The index depends on a combination of a measure of morbidity and the risk of mortality. Methodological debate has tended to concentrate on the technicalities of producing a scale of health; and philosophical argument has concentrated on the ethics of interpersonal comparison. There is little recognition of the fragility of the theoretical assumptions underpinning the proposed combination of morbidity and risk of mortality. The context in which the proposed indices are being developed is examined in Section 2. Whilst most working in the field of health measurement eschew over-simplification, it is clear that the application of micro-economics to management is greatly facilitated if a single index can be agreed. The various approaches to combining morbidity and mortality are described in Section 3. The crucial assumptions concern the measurement and valuation of morbidity; the procedures used for scaling morbidity with mortality; and the role of risk. The nature of the valuations involved are examined in Section 4. It seems unlikely that they could ever be widely acceptable; the combination with death and perfect health poses particular problems; and aggregation across individuals compounds the problem. There are also several technical difficulties of scaling and of allowing for risk which have been discussed elsewhere and so are only considered briefly in Section 5 of this paper.(ABSTRACT TRUNCATED AT 250 WORDS)

Health

[Research in antitumoral chemotherapy. X. Cytotoxic and antitumoral activity of beta-nitrostyrenes and of composed nitrovinyl derivatives].

In previous work the antitumoral cytotoxicity of beta-nitrostyrenes obtained by simplification of the aristolochic acid molecule was demonstrated. The effect of modifying the three characteristic parts of the beta-nitrostyrene molecule has now been investigated. The results obtained in vitro and in vivo allow hypothesis of a mechanism of action for the various beta-nitrostyrene and nitrovinyl compounds studied and definition of the maximum simplification compatible with retention of biological activity.

Animals

[The immunologic tumor diagnosis].

Issuing from a possibility of classification of tumour-associated antigens (TAA), corresponding to themodern state of recognition, the present situation of the immunological tumour diagnostics is discussed. The direct proof of tumour-associated antigens in the blood or in other body fluids, as one of the fundamental possibilities, is hitherto practically matured only for the alpha-fetoprotein and in this case only contribute to the diagnostics of liver carcinomas and malignant teratoblastomas. The determination of the carcinoembryonal antigen (CEA) in the serum or plasm has at present no essential diagnostic significance, may however, be used for the control of the therapeutic effect of cancer of the colon, rectum as well as the stomach. It is reserved for prospective studies to estimate the valency of the determination of CEA or fetal sulphoglycoproteid antigen in the gastric juice for the recognition of early carcinomas of the stomach. At present the proof of an immune response of the tumor carrier to TAA in vitro seems to be more favourable as a second way of the immunological tumour diagnostics. Sensitivity as well as specificity might here at first higher be estimated, when they are theoretically established. Whereas the inhibition test of leucocyte migration and technically similar variants in apparently sufficient specifity have an insufficient sensitivity and thus give too many falsely negative results the mobility test of the electrophoresis of macrophages in the modification of the immunological tumour profile distinguishes itself by a high certainty and by evidence on the probable localisation of the organ and the primary tumour (up to now verified for the cancer of colon and rectum, carcinomas of the stomach). Apart from the research of further principles, however, even for this test technological simplifications are to be found, before a broader use in routine work becomes practicable.

Antibodies, Neoplasm

Simplification of immune adherence hemagglutination test for detection of rabies antibodies in human serum.

In the present work the immune adherence hemagglutination test (IAHA) was standardized in a simplified procedure. This test showed good reproducibility, better than the classical mice serum neutralization test (SN). The tests showed high correlation degree: high titers in one test corresponded to high titers in the other one, and the same occurred with low titers. The IAHA test is extremely simple, fast to perform, and of low cost when compared to tests such as SN or indirect immunofluorescence (IIF). It also proved to be useful in less sophisticated laboratories or even as a screening test for the titration of rabies antibodies.

Antibodies, Viral

An immunoenzymoassay for histamine.

The clinical diagnosis of allergies needs appropriate tools for the measurement of histamine release from leukocyte suspension of affected patients. In the last few years the established fluorometric procedure has been challenged by alternatives like histamine radioimmunoassays (RIA). Although measurements of histamine with the latter methods make this procedure more accessible as a diagnostic tool, further simplifications are always welcomed. A newly developed immunoenzymoassay for histamine is described in the present work and compared to a recent radioimmunoassay. Sensitivity and specificity are shown to be comparable in both procedures.

Acetylcholinesterase

Biomechanics of human movement with applications to the study of human locomotion.

A review of the biomechanics of human movement is presented and covers the neural control of voluntary movement, as it manifests itself in the electromyogram, through to detailed kinetic analyses and simulation studies. The body of knowledge of muscle performance is covered in detail, from the individual motor unit characteristics, through recruitment patterns to the static and dynamic characteristics of the total muscle and its relationship to the electromyogram. A summary of research into the movement of the skeletal (segmental) system itself covers the kinematic data collection systems, the link-segment modeling with anthropometric measures, and the inverse dynamics solution of the joint kinetics. A critique of current simulation models reveals a diversity of simplifications and assumptions that seriously affect the interpretation of results. Similarly, a critical assessment of the literature pertaining to mechanical energy, work, power and efficiency exposes many varied and anomalous techniques and correspondingly confusing interpretations. At all phases of the review the author attempts to reconcile differences, criticize obvious errors, and identify important contributions.

Biomechanical Phenomena

An improvement of the analytical description of temporal variations of plasma and total platelet activities, studied using 75Se-methionin as an in vivo tracer.

In this work we have re-examined our previous model for the analytical description of temporal variations of plasma and total platelet activities, introducing a mathematical simplification by means of elimination of a cumbersome and deforming parameter. We give here 1) interpolation formula 2) complete list of instructions of our program for computer data processing.

Computers

Syntactic and phonological influences on children's articulation.

The effects of syntactic and phonological structure on the consonant articulations of children with phonological deficits were investigated. Three structural variables were studied: syntactic structure (noun phrase, declarative sentence and passive sentence), work structure (monosyllable and disyllable) and word position (initial and final). Syntactic structure and word structure significantly affected the accuracy of articulation and the degree of word simplification. Structural complexity may contribute to overall hierarchial complexity, in turn causing children to simplify their speech.

Articulation Disorders

Cholinergic neuronotrophic factors: fractionation properties of an extract from selected chick embryonic eye tissues.

An aqueous extract derived from selected intraocular tissues of 15-day chick embryos contains a soluble macromolecular agent which is capable of ensuring the survival of 8-day chick embryonic ciliary ganglionic neurons in monolayer culture. When this ciliary neuronotrophic factor (CNTF) was concentrated using ultrafiltration and subjected to Sephadex G100 and G200 chromatography, activity was detected in most of the eluted fractions. A peak of the most active fractions was eluted in a region corresponding to a molecular weight of 35-40 X 10(3) and contained about 20-30% of the applied protein. CNTF activity bound readily to DE-52 cellulose resin at neutral pH and was eluted with NaCl in a narrow region containing about 20-40% of the applied protein. Gel electrophoretic staining profiles of the active DE52 fraction indicated considerable (but still only partial) simplification in protein composition. While significant CNTF activity losses were incurred in response to each of the above treatments, an active material could be conveniently generated in one working day in milligram amounts having a specific activity of 60,000 trophic units/mg protein. This trophic activity is in the same range as that of the only other known neuronotrophic factor, Nerve Growth Factor.

Animals

DNA polymerase III of Mycoplasma pulmonis: isolation and characterization of the enzyme and its structural gene, polC.

Mycoplasmas have originated from Gram-positive bacteria via rapid degenerative evolution. The results of previous investigations of mycoplasmal DNA polymerases suggest that the process of evolution has wrought a major simplification of the typical Gram-positive bacterial DNA polymerase profile, reducing it from three exonuclease (exo)-positive enzymes to a single exo-negative species. The objective of this work was to rigorously investigate this suggestion, focusing on the evolutionary fate of DNA polymerase III (Pol III), the enzyme which Gram-positive bacteria specifically require for replicative DNA synthesis. The approach used Mycoplasma pulmonis as the model organism and exploited structural gene cloning, enzymology, and Pol III-specific inhibitors of the HPUra class as investigative tools. Our results indicate that M. pulmonis has strongly conserved a single copy of a structural gene homologous to polC, the Gram-positive bacterial gene encoding Pol III. M. pulmonis was found to possess a DNA polymerase that displays the size, primary structure, exonuclease activity, and level of HPUra sensitivity expected of a prototypical Gram-positive Pol III. The high level of sensitivity of M. pulmonis growth to Gram-positive Pol III-selective inhibitors of the HPUra type strongly suggests that Mycoplasma has conserved not only the basic structure of Pol III, but also its essential replicative function. Evidence for a second, HPUra-resistant polymerase activity in M. pulmonis is also described, indicating that the DNA polymerase composition of Mycoplasma is complex and closer to that of Gram-positive bacteria than previously thought.

Amino Acid Sequence

Human nutrition--paradoxes of drugs and diet.

Complex historical and other reasons account for public confusion concerning optimal nutritional practice. The mass media are not alone in presenting results of scientific work in non-scientific form. Health professionals, scientists, and people from industry have all contributed to the confusion concerning diet and the public good. Extrapolation from one situation to another, simplification of issues, and biased presentation of data, have intensified the problems. The limited perspective of many experts is frequently coupled with over-enthusiastic promotion of what are really hypotheses rather than established truths. The public good is not being served by the present confusing pattern of paradoxes. There is an urgent need for health professionals to review their presentations to the public such that emerging scientific knowledge is presented effectively in terms of a broad perspective.

Adolescent

SV-40 transformation: effect on GM2 ganglioside in cultured cell lines.

In previous work, we observed the presence of substantially elevated levels of GM2 after Simian Virus 40 (SV-40) transformation of human fetal brain cells. This elevated level of GM2 contrasted with the reports of many other investigators who had often observed decreased levels of GM2 and a simplification of ganglioside pattern in various non-neural rodent cell lines. In order to determine if the increase in GM2 in the transformed human brain cells would also be found in transformed rodent brain cells, we analyzed ganglioside changes after transformation in mouse brain cell lines and observed the increase in GM3 and low levels or lack of GM2 usually noted in rodent SV-40 transformed cell lines. In addition, we analyzed changes after SV-40 transformation in three human fibroblast lines and found that all three lines contained substantially elevated levels of GM2 after SV-40 transformation. As a result of this study, our earlier work on SV-40 transformed human brain cells, and occasional other reports of high levels of GM2 in human SV-40 transformed cell lines, elevated levels of GM2 may be considered a marker for SV-40 transformed human cells of both fibroblastic and neural origin.

Animals

[Test report on the system components for film processing by the middle-format technology].

Industrially developed accessories for use with medium-format equipment, which have been tested in a-clinical settery, were evaluated separately. The automatic mounting system (Delcadro) with the plastic mount (Cadrix) was accepted by all of our colleagues, and was rated as an advantage, with hardly any reservations. A slight modification is needed in the design of the mounts. This equipment would be a desirable addition to our own equipment for routine work. The daylight system (camera magazine and feeder) is, in principle, certainly a step in the right direction. Handling of the magazine proved to be too complicated and it was prone to malfunctions. Simplification, especially of the loading mechanism, would be desirable. The film feeder is designed for use with conventional roll processing machines. In our opinion, a feeder will always be put to full use if the films processed in this machine are mainly or exclusively of middle format; the darkroom is not permanently staffed and/or adaptation to an existing daylight system (large formats) has already been effected and/or depending on availability, both large and medium size-formats can be processed fully automatically as quickly as possible. However, if films of various formats are processed by an assistant in a darkroom, it is possible to deal with the total quantity of films faster than with a feeder by inserting 3 or 4 medium-format films (or 2 or 3 large-format films) simultaneously. The Heliomat film viewer offers impressive reproductions of 100 mm film on a glare-free glass screen.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic

An analytical solution for the dynamic control of multileaf collimators.

All current optimization techniques in radiation therapy benefit from the use of strongly non-uniform radiation beams. The most flexible way of generating these fields under real time control is by elementary beam scanning and/or dynamic multileaf collimation. In this work general analytical expressions are derived for the required motion of the collimator leaves to achieve a desired energy fluence distribution or collimator opening density in the patient in the shortest possible time. By simplification of the general expressions the equations of motion have been derived for both the shrinking field and the curtain shutter techniques with the associated approximations clearly quantified. The mechanical limitations on leaf motion, caused by the finite velocity and acceleration, are taken into account. It is shown that almost any desired energy fluence distribution can be created even when the limitations on velocity and acceleration are considered. The basic rule with the curtain shutter technique is that when the energy fluence gradient along the direction of motion of the leaves is positive, the leading leaf should move at maximum speed and the lagging leaf should modulate the field. In regions where the gradient is negative the lagging leaf should instead move at full speed and the leading leaf should modulate the field. The overall treatment time is then proportional to the total increment in energy fluence or opening density between consecutive minima and maxima. For energy fluence profiles with numerous high peaks the treatment time may therefore increase considerably over that for conventional uniform dose delivery. However, in general the treatment time is prolonged by a factor of about two compared to a traditional uniform treatment. Obviously the method developed here for multileaf collimators is also suitable for simple block collimators since it can be used to deliver arbitrary regular or irregular 'dynamic wedge' profiles along the direction of motion of the collimator blocks.

Humans

Reduction syringe liposculpturing.

The use of the syringe has been an advance in reduction and incremental liposculpturing. A real democratization in the medicosurgical group has been possible due to the simplification of the equipment. The shock-absorbing action of the syringe makes the operation safer and allows more fat to be removed and better results to be obtained because one does perfectly symmetrical work. The syringe is a unit of measurement in this surgery of volume.

Adipose Tissue

[Hypnosis and cancer: a working hypothesis. Initial notes].

Hypnosis has been used to resolve stress and anxiety following profound psychological-behavioural changes occurring in the cancer sufferer from the moment of diagnosis. It is stated that hypnosis is useful in improving sick persons' quality of life through the control of stress reactions, simplification of treatment and facilitation of rehabilitation, both within the family and socially. Through deep seated psycosomatic interconnections, psychological attitude can affect organic reaction to all disease, cancer included.

Humans