Disease

This paper examines what it is for a condition to be a disease. It falls into two sections. In the first I examine the best existing account of disease (as proposed by Christopher Boorse) and argue that it must be rejected. In the second I outline a more acceptable account of disease. According to this account, by disease we mean a condition that it is a bad thing to have, that is such that we consider the afflicted person to have been unlucky, and that can potentially be medically treated. All three criteria must be fulfilled for a condition to be a disease. The criterion that for a condition to be a disease it must be a bad thing is required to distinguish the biologically different from the diseased. The claim that the sufferer must be unlucky is needed to distinguish diseases from conditions that are unpleasant but normal, for example teething. Finally, the claim that for a condition to be a disease it must be potentially medically treatable is needed to distinguish diseases from other types of misfortune, for example economic problems and legal problems.     

CURRENT NOTES AND NOTICES

These are collated by Gwen Bonham, the Union's Administrative Secretary. Requests for the publication of information or other required assistance will be sympathetically considered. Publicity will gladly be given to relevant grants and awards that can be applied for, and to new societies which might be of interest to our readers. Details of conferences and meetings will also be included if sent to the Administrative Secretary at least 6 months in advance of the event. All items for Current Notes and Notices should be sent to the BOU, % The Natural History Museum, Tring, Hertfordshire HP23 6AP, UK .     

Marital therapy for the elderly.

Little attention has been paid to marital therapy for the elderly in spite of its relevance to morale and emotional problems. Physical illness is of particular significance in altering the dynamics of the marital relationship. Retirement and financial problems, as well as changes in sexual activity and gender roles, are also important. However, radical changes in patterns of behaviour cannot be expected. Therapeutic techniques must be altered for this age group, and the therapist must be active, giving and concretely helpful. As with therapy for younger couples, children may need to be involved in the therapy sessions. Family physicians should be a main source of help for marital problems among the elderly. However, because problems related to countertransference must be faced, working with the elderly will not be for everyone.     

Performance modeling and simulation of biochemical process sequences with interacting unit operations

Many biochemical processes consist of a sequence of operations for which optimal operating conditions (setpoints) have to be determined. If such optimization is performed for each operation separately with respect to objectives defined for each operation individually, overall process performance is likely to be suboptimal. Interactions between unit operations have to be considered, and a unique objective has to be defined for the whole process. This paper shows how a suitable optimization problem can be formulated and solved to obtain the best overall set of operating conditions for a process. A typical enzyme production process has been chosen as an example. In order to arrive at a demonstrative model for the entire sequence of unit operations, it is shown how interaction effects may be accommodated in the models. Optimal operating conditions are then determined subject to a global process objective and are shown to be different from those resulting from optimization of each separate operation. As this strategy may result in an economic benefit, it merits further research into interaction modeling and performance optimization.     

The Genetic Improvement of Entomopathogenic Nematodes and Their Symbiont Bacteria: Phenotypic Targets, Genetic Limitations and an Assessment of Possible Hazards

The methodologies of classical genetics and genetic engineering can be used for the genetic improvement of entomopathogenic nematodes (EPNs) and their symbiont bacteria. Many of the complex behavioural and physiological traits which are targets for genetic improvement are likely to be controlled polygenically, thus selective breeding for improvements to these traits would be appropriate. Much basic research needs to be carried out before researchers will be able to effect improvements to EPNs and their symbionts by genetic engineering. There is a lack of basic information on the genetics and biochemistry of the characteristics that might be altered by transgenic methods in EPNs, and their bacteria, and existing transformation protocols need to be made more effective.     

A proposal on metrics for identification using nucleic acid sequences

Abstract The need is stressed for attempts to be made to permit diagnostic nucleic acid sequences to be used in a quantitative manner. Sequence differences or binding values should be converted to a distance measure and from this an ultrametric tree should be constructed. A single quantitative determination can yield considerable information about the likely identity of an unknown microorganism when the distance obtained from the sequence is compared with the tree. The concept is illustrated by hypothetical species and genus subsequences, and it is suitable both for successive use of hierarchical subsequences and for automated identification. It is pointed out that entirely specific subsequences for higher taxa may be difficult to discover. These principles will be useful for the future design of diagnostic sequences, including possible application to DNA-DNA pairing.     

CURRENT NOTES AND NOTICES

These are collated by Gwen Bonham, the Union's Administrative Secretary. Requests for the publication of information and other assistance will be considered sympathetically. Publicity will be given to relevant grants and awards that can be applied for, and to new societies which might be of interest to our readers. Details of conferences and meetings will also be included if sent to the Administrative Secretary at least 6 months in advance of the event. All items for Current Notes and Notices should be sent to the BOU , % The Natural History Museum, Tring. Hertfordshire HP23 6AP, U.K. Fax No. 0442–890693 .     

Procedures for handling fresh stallion semen

Handling procedures for semen to be used at the stud-farm and for transport are reviewed. Proper handling of semen is required throughout the entire process, from semen collection to the insemination of the mare. Semen shall not be exposed to mechanical damage, light, cold or heat. All equipment that comes in contact with semen must be warm, clean, dry and free from toxic residues. Skim-milk extender appears to be the medium best suited for the preservation of stallion semen during cooling and storage. When used immediately, semen is usually extended 1:1 (v:v), but for transport, concentrations of 25 to 100 x 10(6) spermatozoa/mL are recommended. The proportion of semen plasma should be reduced to < 20%. by centrifuging, by collecting only the first 3 sperm-rich fractions, or by substantially diluting of the ejaculate. The storage temperature can be between 20 to 15 degrees C, if shipment time is no more than 12 h; for longer storage, temperatures < 10 degrees C are recommended. Semen can be cooled rapidly from 35 to 19 degrees C. In the temperature zone between 19 and 8 degrees C, stallion spermatozoa are sensitive to cold shock, and the cooling rate should be slowed to 0.05 degrees C/min. Rapid cooling can be resumed below 8 degrees C. At low temperatures, removal of oxygen-rich air is beneficial for the survival of spermatozoa. The Equitainer transport container keeps a constant temperature of 5 degrees C for 48 h and is therefore recommended for transportation lasting over 24 h.     

The hospital component of vocational training for general practice.

Trainees and educationalists in general practice have some grounds for suggesting that the hospital component of vocational training should be restructured and teaching improved. However, the implications for other trainees and secondary care have to be considered. Changes that are needed include a curriculum for senior house officers in each specialty; appointment of training consultants with the necessary skills; and a different attitude by everyone towards study leave, including arrangements for funding. The optimum duration of hospital posts for trainees in general practice might be shorter than now, but the effects on others must be considered and competencies guaranteed in a briefer training period. Changes in the regulations for vocational training could help to improve specialist experience if trainees in general practice were allowed to be supernumerary. Alternatively, senior house officer posts for trainees in general practice could be split between secondary and primary care, thus encouraging a broader perspective.     

Confidence intervals for genotype relative risks and allele frequencies from the case parent trio design for candidate-gene studies

OBJECTIVES: Confidence intervals for genotype relative risks, for allele frequencies and for the attributable risk in the case parent trio design for candidate-gene studies are proposed which can be easily calculated from the observed familial genotype frequencies. METHODS: Likelihood theory and the delta method were used to derive point estimates and confidence internals. We used Monte Carlo simulations to show the validity of the formulae for a variety of given modes of inheritance and allele frequencies and illustrated their usefulness by applying them to real data. RESULTS: Generally these formulae were found to be valid for 'sufficiently large' sample sizes. For smaller sample sizes the estimators for genotype relative risks tended to be conservative whereas the estimator for attributable risk was found to be anti-conservative for moderate to high allele frequencies. CONCLUSIONS: Since the proposed formulae provide quantitative information on the individual and epidemiological relevance of a genetic variant they might be a useful addition to the traditional statistical significance level of TDT results.     

IS SEX‐SELECTIVE ABORTION MORALLY JUSTIFIED AND SHOULD IT BE PROHIBITED?

In this paper we argue that sex-selective abortion (SSA) cannot be morally justified and that it should be prohibited. We present two main arguments against SSA. First, we present reasons why the decision for a woman to seek SSA in cultures with strong son-preference cannot be regarded as autonomous on either a narrow or a broad account of autonomy. Second, we identify serious harms associated with SSA including perpetuation of discrimination against women, disruption to social and familial networks, and increased violence against women. For these reasons, SSA should be prohibited by law, and such laws should be enforced. Finally, we describe additional strategies for decreasing son-preference. Some of these strategies rely upon highlighting the disadvantages of women becoming scarce, such as lack of brides and daughters-in-law to care for elderly parents. We should, however, be cautious not to perpetuate the view that the purpose of women is to be the consorts for, and carers of, men, and the providers of children. Arguments against SSA should be located within a concerted effort to ensure greater, deeper social and cultural equality between the sexes.     

Legal Implications of Sterilization

Sexual sterilization is legal when it is an integral part of a procedure for the preservation of the life or health of a patient. Done for other reasons it may not be illegal, but this has not been tested in Canadian courts. It is, broadly speaking, a surgical procedure; it is commonly, but not always, successful; complications, while rare, do occur; the results tend to be irreversible. The same end, the prevention of pregnancy, may be attained by other methods which are safer, less liable to complications, less permanent and so should be used unless contraindicated. Patients'' statements that they do not like contraceptives should not be accepted as a reason for sterilization. Sexual sterilization should be reserved for those occasions when it is necessary for the preservation of the health or life of the individual who is to be sterilized.     

Interferon induction and utilization

The interferon mechanism offers the hope for moderate to high level prophylactic immunity of broad antiviral spectrum but of relatively short duration. Economic and biological considerations offer little hope for utilization of exogenous interferon as a prophylactic or therapeutic substance, unless but a small part of the total molecule be found to carry the activity. The real promise for interferon application is in the administration of suitable inducers so as to cause the body to produce and distribute its own interferon. Certain ribonucleic acids (RNA's) offer hope for high level potency as inducers without adverse effect. The condition for interferon induction by ribonucleic acids appears to be double- or multistrandedness and freedom from inhibitors. These can be of biologic or synthetic origin. The mechanism of action of interferon is not fully understood but appears to fit into the Jacob-Monod model involving two phases: first, a derepression by the inducer to cause the cell to form interferon and second, a derepression by interferon to cause recipient cells to form the active substance which acts by preventing translation from viral messenger RNA. Double or multistranded RNA of viral or other origin appears to be unique to the cell and serves as the alert to it to produce interferon in phase 1. Greatest need for interferon is clearly for those diseases in which there is a multiplicity of immunologic types in excess of the numbers which could be put into a vaccine as, e.g., the common cold and enteric viruses. There might be some overall therapeutic benefit also if inducer were given early enough in infection. Special value for interferon induction might derive by administration in early life before the development of immunologic maturity, as a means for preventing infection with oncogenic or other viruses. Additionally, suitable inducers might be capable of interrupting the reinfection cycle in virus-dependent malignancies. The favorable outlook for interferon utilization must always be tempered with the realization that under certain as yet undiscovered situations, adverse rather than beneficial effects might result from indution of interferon. It is not impossible that in certain special circumstances, as in ordinary immunologic responses, it might be more beneficial to negate rather than to promote the effect.     

Strategies for the development of bacterial transformation systems

An effective transformation system is a prerequisite for facile genetic manipulation of bacteria. Bacteria may be naturally competent for transformation or may be treated with various agents, such as Tris buffers or divalent metal ions, to induce competence. Transformation can also be accomplished by electroporation, or by fusion of protoplasts with PEG in the presence of transforming DNA. Unfortunately, the mechanism by which cells become permeable to DNA and the process by which DNA enters the cells is frequently unknown. In order to establish a transformation system for an untransformable bacterium, recipient strains and transforming DNA must be carefully selected. Since it is impossible to predict in advance which method of transformation will be successful with a particular bacterial strain, several techniques are usually evaluated. This review describes a number of factors that appear to be critical for developing a transformation system and presents a strategy for experimentation with novel bacteria.     

CURRENT NOTES AND NOTICES

These are collated by Gwen Bonham. Requests for the publication of information and other assistance will be considered sympathetically. Publicity will be given to relevant grants and awards that can be applied for and to new societies which might be of interest to our readers. Details of conferences and meetings will also be included if sent at least 6 months in advance of the event, and news of members' activities is always welcome. All items for Current Notes and Notices should be sent to BOU, % The Natural History Museum, Tring, Hertfordshire HP23 6AP. UK. Fax: 01442 890693.     

Towards reliable spike-train recordings from thousands of neurons with multielectrodes

The new generation of silicon-based multielectrodes comprising hundreds or more electrode contacts offers unprecedented possibilities for simultaneous recordings of spike trains from thousands of neurons. Such data will not only be invaluable for finding out how neural networks in the brain work, but will likely be important also for neural prosthesis applications. This opportunity can only be realized if efficient, accurate and validated methods for automatic spike sorting are provided. In this review we describe some of the challenges that must be met to achieve this goal, and in particular argue for the critical need of realistic model data to be used as ground truth in the validation of spike-sorting algorithms.     

The use of biomarkers in surveillance, medical screening, and intervention

Building on mechanistic information, much of molecular epidemiologic research has focused on validating biomarkers, that is, assessing their ability to accurately indicate exposure, effect, disease, or susceptibility. To be of use in surveillance, medical screening, or interventions, biomarkers must already be validated so that they can be used as outcomes or indicators that can serve a particular function. In surveillance, biomarkers can be used as indicators of hazard, exposure, disease, and population risk. However, to obtain rates for these measures, the population at risk will need to be assessed. In medical screening, biomarkers can serve as early indicators of disease in asymptomatic people. This allows for the identification of those who should receive diagnostic confirmation and early treatment. In intervention (which includes risk assessment and communication, risk management, and various prevention efforts), biomarkers can be used to assess the effectiveness of a prevention or control strategy as well as help determine whether the appropriate individuals are assigned to the correct intervention category. Biomarkers can be used to provide group and individual risk assessments that can be the basis for marshalling resources. Critical for using biomarkers in surveillance, medical screening, and intervention is the justification that the biomarkers can provide information not otherwise accessible by a less expensive and easier-to-obtain source of information, such as medical records, surveys, or vital statistics. The ability to use validated biomarkers in surveillance, medical screening, and intervention will depend on the extent to which a strategy for evidence-based procedures for biomarker knowledge transfer can be developed and implemented. This will require the interaction of researchers and decision-makers to collaborate on public health and medical issues.     

Key issues in managed competition.

All managed competition proposals for health system reform must confront several key issues. The premiums paid to health care purchasing cooperatives will need to be subsidized for those who cannot pay full fare; the amount and sources of the subsidies are controversial political issues. The payments passed on by purchasing cooperatives to health plans must be risk adjusted to account for differences in the health care needs of their enrolled populations. This is essential to create a level playing field for competition and to eliminate incentives for plans to use risk assessment for attracting enrollees. The data and methods needed for risk adjustment, however, are not adequate at present. The Clinton Administration''s plan to limit expenditure increases raises a host of thorny issues. Maintaining quality of care will require health plan quality report cards to be supplemented by external quality assurance systems. Assuring quality will be particularly problematic for traditional indemnity plans. The structure and governance of the system, administration simplification, and other issues need to be addressed. The size and voluntariness of the purchasing cooperatives greatly influence all of these considerations. Physicians should inform their political representatives on how these issues should be resolved as compromise bills are drafted by the United States Congress this year.     

Ethical and regulatory issues arising from proteomic research and technology

Over the last two decades, medical research has begun to make extensive use of products of human origin in therapeutics, oncology, and most recently, in genetic diseases. This has raised many ethical issues involving patient rights, including issues of consent. Besides informed consent, researchers should address several topics when designing studies using human tissues. Reward for the patient should be kept minimal. Sample transfer should be organized along non-profit lines, at least in Europe. Sampling procedures should be at no risk for human volunteers, and at minimal risk for patients. Biosafety aspects should be addressed, in particular when international collaborations are intended or when collaboration is existing between academia and industry. Regulations on importation and exportation of human tissues should be observed. Data acquisition and storage should be addressed in accordance with national data protection regulations, in particular when using computerized databases. If follow-up information is to be taken, the authorization for such information should be requested. The right for patient's information (or for no information) on the research results should also be addressed. The issues of validation and patenting should be also solved, usually by informing the patient that he/she will have no commercial rights on potential research results. The patient should be told if the samples are transferred to another research laboratory or private company. Samples and related data should be destroyed on request at any time point during the course of the study. If possible, traceability of the donor should be ensured.